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1
Massinga, Pedro Horacio. "Gel-based solid dosage form for pesticide delivery." Diss., University of Pretoria, 2008. http://hdl.handle.net/2263/23498.
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The aim of this research was to develop a solid dosage form containing 1.5 g of the pesticide cypermethrin. The dosage should be stable in a tropical climate. In addition, it is to disintegrate and disperse in 10 L of tap water within 3 minutes. Such dissolution should yield a 150 ppm dispersion of cypermethrin, stable for at least one week. This provides for a dip dispersion to treat ticks and fly infestation on livestock. A new solid dosage was formulated as the scope of this research. It is a gel-based solid dosage form. Polymer electrolyte ASP4 - a copolymer of methacrylic acid, ethyl acrylate and diethyl maleate, was used to produce the gel. Preliminary tests revealed that ASP4- based gel, on its own, failed to meet the required dissolution time of 3 minutes. Strong entanglements of ASP4 chains impeded rapid dissolution. These strong entanglements occurred owing to the use of a high concentration of ASP4. Reducing the concentration of ASP4 yielded a solution of high viscosity instead of a gel. It was therefore decided to Gel-based solid dosage form for pesticide delivery use a superabsorbent (Product Z1069) in conjunction with ASP4 to produce the gel. Product Z1069 is a cross-linked sodium polyacrylate. Before producing the gel, a 1:1.5 by mass oil/water (O/W) emulsion was prepared using the phase-inversion route. The water (W) phase comprised 85.9% distilled water, 3.9% ASP4 at 20% dispersion, 8.6% sodium carbonate (0.5 M) and 1.6% Emulsogen EL. All concentrations are indicated in mass %. The oil (O) phase consisted of 76.9% cypermethrin, 19.3% Solvesso S200 and 3.8% Phenyl Sulphonate CA, also by mass. This emulsion was gelled by adding the superabsorbent Product Z1069 (ca. 37.5% by mass relative to the W phase of the emulsion). The superabsorbent strongly absorbed water, depleting it from the emulsion. This resulted in an increase of the effective concentration of ASP4 in the water phase of the emulsion. This increase of the polymer electrolyte concentration brought about a gel-like state corresponding to the desired solid dosage form. Rheometry confirmed that the dosage form maintained a solid gel-like consistency at 50°C. The dosage contained 24.6% m/m cypermethrin. Thus, the required dosage of 1.5 g was achieved in pellets weighing ca. 6.1 g. Such pellets rapidly disintegrated with mild stirring in 10 L of tap water. Complete pellet disintegration and active dispersion occurred within 2.5 minutes at ambient temperature (25 ± 2°C).Dissertation (MSc)--University of Pretoria, 2008.
Chemistry
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Raiwa, Araya [Verfasser]. "Formulation development strategies for oral extended release dosage form / Araya Raiwa." Berlin : Freie Universität Berlin, 2011. http://d-nb.info/1025490363/34.
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Nqabeni, Luxolo. "Development of an antiretroviral solid dosage form using multivariate analysis." Thesis, Nelson Mandela Metropolitan University, 2007. http://hdl.handle.net/10948/705.
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The aim of pharmaceutical development is to design a quality product and the manufacturing process to deliver the product in a reproducible manner. The development of a new and generic formulation is based on a large number of experiments. Statistics provides many tools for studying the conditions of formulations and processes and enables us to optimize the same while being able to minimize our experimentation. The purpose of this study was to apply experimental design methodology (DOE) and multivariate analysis to the development and optimization of tablet formulations containing 150 mg lamivudine manufactured by direct compression.
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Ranmal, S. R. "Acceptable medicines for children : end-user insights to support dosage form design." Thesis, University College London (University of London), 2015. http://discovery.ucl.ac.uk/1469794/.
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Evolving regulatory reforms have strengthened the global focus towards developing age- appropriate and acceptable formulations for paediatric patients. The European Medicines Agency (EMA) also mandates that acceptability of paediatric preparations should be evaluated with children as an integral part of pharmaceutical and clinical development. A review of literature highlights the current paucity of evidence to support the development of dosage forms that are suitable for children of different ages and health backgrounds. Important knowledge gaps also exist in the methodological considerations for conducting acceptability studies. The overall aim of this research was to determine the attitudes, preferences and behaviours of children, caregivers and healthcare professionals towards solid oral dosage forms. Age- adapted questionnaires were systematically developed and pre-tested in collaboration with young people, in keeping with the principles of patient and public involvement in research. A diverse sample of 590 school children and adolescents and over 400 caregivers were surveyed in hospitals, community pharmacies and schools. Attitudes towards dosage forms differed primarily based on age and prior use. Precedence for chewable dosage forms and tablets was identified, while capsules and multiparticulates administered with food were less acceptable. Another aspect of the research identified the prevalence of swallowing difficulties in healthy young adults. These participants showed a preference for taking two smaller dosage forms over a larger size, and for capsules over tablets. In an acceptability trial with placebo capsules, over 95% of young adults were able to swallow size #1 capsules. The inclusion of flavour had variable effects on acceptability . Healthcare professionals showed reservations towards solid oral dosage forms and many favoured liquid medicines for paediatrics. This thesis highlights the gap between regulatory expectations, industrial feasibility and clinical ideals. This should be addressed, to ensure that legislative reforms and global initiatives will have a positive impact on paediatric therapeutics in practice.
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Injety, Sahana. "Formulation of a nevirapine co-crystal as a liquid dosage form." University of the Western Cape, 2016. http://hdl.handle.net/11394/5060.
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Magister Pharmaceuticae - MPharmCo-crystals are a solid phase phenomena that could enhance the physicochemical properties of an active pharmaceutical ingredient. A co-crystal has never been incorporated into a liquid dosage form with the assurance of maintaining its co-crystal state until absorption under defined conditions. This study aims to develop a liquid formulation with a nevirapine co-crystal. A protocol was developed to investigate all the five co-formers that were used to make the nevirapine co-crystals to-date. The most appropriate co-former was selected for a liquid dosage form to study the integrity and the scaling up of the co-crystal in a suspension formulation. Co-formers used were viz. saccharin, glutaric acid, salicylic acid, rac-tartaric acid and maleic acid. These were characterized according to their physical, chemical, pharmacological and pharmaceutical properties. A grading scale was used to select the most appropriate co-former for a suspension formulation. Comparatively, saccharin produced the best combination of physical, chemical, pharmacological and pharmaceutical properties, especially with regard to the particle size and the specific gravity which proved to be very useful as optimal criteria for suspension formulation. Upon selection of the ideal co-former, scale-up of the nevirapine saccharin co-crystal was performed from a small scale of 350 mg to a large scale of 5 g. Nevirapine-saccharin (NVSC) co-crystals were prepared utilizing the slow evaporation technique, using methanol as the solvent and the percentage yield of the co-crystals were > 80 %. The identity of co-crystals was confirmed using hot stage microscopy (HSM), differential scanning calorimetry (DSC), fourier transform infra- red (FTIR) and thermogravimetric analysis (TGA). Three co-crystal suspension formulations were prepared using the excipients identified in the branded, Viramune® suspension, with each formulation containing viscosity enhancers such as aerosil 200, carbopol 971G and carbopol 974P. To ascertain the co- crystal integrity in the suspension, it was filtered and the filtrate was identified with DSC and FTIR while the filtered solution was identified with ultraviolet spectroscopy (UV). The co-crystal suspension formulation with optimal pH, viscosity and assurance of co-crystal integrity was the carbopol 974P formulation. The UV and DSC of the filtrate of the suspension revealed that the co-crystal had not separated into its individual components and remained intact while in suspension form irrespective of the excipients added. This formulation proceeded to the quality control stage. It was assessed for its pH, viscosity and dissolution according to the USP 32 standards and compared to the branded nevirapine suspension, Viramune ®, presently on the market. The suspension was characterized for particle size, zeta potential and polydispersity index. The dissolution results assayed by High Performance Liquid Chromatography (HPLC) revealed a drug release of 86 % in the Viramune® suspension while the NVSC co- crystal suspension achieved a drug release of 94% within 30 minutes of dissolution.
National Research Foundation (NRF)
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Phillips, Justin. "Dextrin nanocomposites and deep eutectic solvents as matrices for solid dosage forms." Diss., University of Pretoria, 2020. http://hdl.handle.net/2263/81724.
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Controlled-release formulations for pesticide applications act as depot systems that continuously
release the active ingredients into the environment over a speci ed period,
usually from months to years. However, some applications require fast-dissolving drug
delivery. The interest of this research is in fast-release of water-insoluble pesticides into
aquatic environments. This study considered the use of dextrin starch and urea eutectics
as fast release, solid dosage carrier forms that contain an active ingredient. The chosen
active for this study is an acaricide called amitraz (N-methylbis-(2,4-xylyliminomethyl)-
methylamine). The focus is on matrix-based dosage forms such as tablets, granules or
bres that either disintegrate or dissolve to release a water-insoluble active. These types
of dosage forms can be fabricated using processes such as lyophilisation, spray drying,
solvent casting, hot melt extrusion, compression moulding, wet granulation, compaction
and electrospinning. A simple melt-casting procedure has been discussed in the present
work.
Dextrin is a water-soluble form of partially hydrolysed starch and is a promising candidate
matrix material for dissolving solid dosage forms. The molecular weight of the
dextrin was analysed with MALDI-TOF methods and rheological relations. Glycerolplasticized
thermoplastic dextrin-based nanocomposites were prepared with a twin-screw
extrusion-compounding process. The nano llers included a layered double hydroxide
(LDH), cellulose nano bres (CNF) and stearic acid. The time-dependent retrogradation
of the compounds was monitored by X-ray di raction (XRD) and dynamic mechanical
thermal analysis (DMA). XRD showed that the inclusion of stearic acid in the formulations
led to the formation of an amylose-lipid complex and a stable crystallinity during
ageing.
Dissolution rates in water for samples containing dextrin starch, were characterised using
an iodine indicator and UV-visible spectroscopy. High pressure di erential scanning
calorimetry (HPDSC) indicated that the addition of stearic acid led to the formation of
amylose-lipid complexes (ALC's). An additive system containing stearic acid and CNF
was deemed suitable for compounding with amitraz. Compounding at temperatures
above the melting point of the latter led, on dissolution in water, to the release of much
ner particles of the acaricide, which was con rmed with particle size analysis (PSA). The addition of the acaricide caused an apparent increase in the dissolution rate of the
thermoplastic dextrin.
Two eutectic urea systems were considered for casting with amitraz. A eutectic system
of urea and acetamide was found to display a melting point of 44 C at a 37 wt.%
urea composition. The other system consisting of urea and 1,3-dimethylurea displayed a
eutectic point at 32 wt.% urea composition which melted at 59 C. Di erential scanning
calorimetry (DSC), however, con rmed a melting point depression due to a high moisture
content caused by the compounds high hygroscopicity. The endotherm of the sample
containing no excess moisture showed a melting point of 70 C. The 1,3-dimethylurea
system was deemed suitable for casting with amitraz. XRD of the eutectic composition
indicated a small amount of co-crystallisation. The samples were cast as disks of various
diameters while keeping the height of the disks constant. The creation of the cast disks
showed automatic generation of a nely dispersed form of the active through the process
of melting the deep eutectic solvent, the dissolution of the active and its phase separation
on cooling and solidi cation of the eutectic. This implies that ne grinding of the actives
might not be necessary. Eutectic casts containing 20 wt.% amitraz dissolved at a slower
rate than casts not containing the hydrophobic active ingredient. The advantageous
features of these casts were exempli ed using the acaricide incorporated into the urea &
1,3-dimethylurea eutectic.
This work provides two safe, biodegradable and water soluble materials for use as a
matrix to contain active ingredients. One material, the eutectic organic salt casts, can be
produced at low temperatures (<100 C) and can be directly cast into storage containers.
The complete dissolution of the cast compounded with a hydrophilic active is rapid (4-6
min). The second material, a thermoplastic dextrin, was melt compounded in an extruder
at temperatures not exceeding 120 C. This compound containing 20 wt.% of the active
dissolved over a 12 hour period. Dextrin, known to be widely used as an adhesive, will
aid in the adhesion of the active ingredient to the surface where it must be used.Dissertation (MEng (Chemical Engineering))--University of Pretoria, 2019.
PAMSA
Department of Science and Innovation under Grant DST/CON 0004/2019
Chemical Engineering
MEng (Chemical Engineering)
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Bohloko, Ntseliseng Selloane. "Development and formulation of an intranasal dosage form for cyclizine hydrochloride / Ntseliseng Selloane Bohloko." Thesis, North-West University, 2004. http://hdl.handle.net/10394/403.
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A comprehensive review of the nasal route of administration, in particular the nasal drug
delivery system has been presented. The physicochemical properties, mode of action and
pharmacology of H1-receptor antagonists, in particular cyclizine HCl, have been
highlighted. The techniques for the assessment of toxicity (in-vitro ciliary beat frequency
(CBF) studies for human nasal explants and morphology studies of the rat nasal mucosa),
synthesis of cyclizine lactate, solubility studies of both cyclizine HCI and cyclizine
lactate, viscosity determination of the gel formulated and assessment of the deposition
and distribution of the hydroxypropylmethyl cellulose (HPMC) dispersions within the
human nasal cavity model were conducted.
In this study, preliminary studies on the toxicity of the various formulation components
(excipients and active ingredient) were carried out. Results from these studies indicated
that for both the excipients and the drug, pH significantly affects the ciliary motility
hence all ciliary beat frequency determinations were conducted at nasal pH. Furthermore,
effects of the various concentrations (0.0625%(w/v), 0.125%(w/v), 0.25%(w/v),
0.5%(w/v) and l%(w/v)) of the excipients on ciliary motility were investigated.
Transmission electron microscopy (TEM) studies proved useful in evaluating the
integrity and changes in the surface morphology of the rat nasal mucosa post treatment
with the various excipients (carboxymethyl cellulose, hydroxypropylmethyl cellulose,
trimethyl chitosan 36.3% DQ, Carbopol P934 and polysorbate-80) at varying
concentrations.
Of the excipients investigated, hydroxypropylmethyl cellulose (HPMC) showed ciliofriendliness
since there was no apparent ultra structural damage, although a slight
decrease in ciliary beat frequency (CBF) was observed at the highest viscosity. Moreover,
hydroxypropylmethyl cellulose (HPMC) is said to be a bioadhesive excipient, which
would therefore confer its bioadhesive properties to the intranasal preparation to enhance
the retention time between the absorbing mucosa and the drug and hence increase nasal
drug absorption. This excipient was therefore selected as the ideal for use in the
formulation of the intranasal preparation.
The aqueous solubility of a drug plays an important role in nasal administration since it is
required that the drug component be applied in a limited volume of about 200pl. To
enhance the aqueous solubility of the sparingly water-soluble cyclizine HCl, a lactate salt
was synthesised and characterised. This compound was found to be highly soluble in
water. The intranasal preparation was therefore manufactured using the lactate form of
cyclizine.
A single blind study was conducted to determine and compare the pharmacokinetic
parameters for both Valoid oral tablets containing 100mg cyclizine HCl (reference
drug) and cyclizine lactate intranasal preparation 125mglml (study drug). The results
obtained indicated a significant improvement in the bioavailability of cyclizine. For oral
administration Cmax = 200.79ng/ml at tmax = 5.57h and for the intranasal preparation Cmax = 5354.22ng/ml at tmax = 1.59h.
A 19.2-fold increase in drug bioavailability was observed after intranasal administration
(AUCin = 122860.70ng/ml/h) compared with oral administration (AUCpo =
5943.48ng/ml/h). This enhanced bioavailability through nasal administration indicated
that enhanced nasal drug absorption and hence increased bioavailability not only depends
on the favourable anatomical and physiological characteristics of the nasal mucosa but
possibly on the inherent physico-chemical characteristics of the drug molecule and the
formulation components. Thus chemical modification of the sparingly water-soluble
cyclizine HCl to the highly water-soluble cyclizine lactate facilitated the dissolution of
more solute in a limited volume of solvent. This new feature therefore may have
impacted positively to the transport of cyclizine across the nasal mucosa. Furthermore,
the hydroxypropylmethyl cellulose (HPMC), component of the formulation, could have
conferred its mucoadhesive properties to the preparation. Perhaps it increased the
retention time of the dosage form within the nasal passages through bond formation with
the nasal mucosa thereby increasing the contact time between the absorbing mucosa and
the dosage form. This interaction between the mucoadhesive and the nasal mucosa may
have resulted in the modification of tissue permeability (possibly transient opening of the
tight junctions) and eventual increase in the drug penetration/absorption.Thesis (Ph.D. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2004.
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Patel, Fathima. "The development and assessment of a generic carbamazepine sustained release dosage form." Thesis, Rhodes University, 2006. http://eprints.ru.ac.za/1339/.
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Lopez, Lopez Felipe. "Better medicines for children : elucidating patient acceptability to guide flexible solid oral dosage form design." Thesis, University College London (University of London), 2017. http://discovery.ucl.ac.uk/10028121/.
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A medicine will not elicit its desired therapeutic effect if the patient is not able or willing to take it. The specific needs of the target population must be taken into account in the design of medicines. Evaluation of the effect of formulation factors on patient’s acceptability could guide the development of better medicines for children. Flexible solid oral dosage forms, including multiparticulates and (oro)dispersible formulations, offer advantages over conventional solid and liquid dosage forms to meet the needs of paediatric patients. These advantages include favourable stability profile, suitability for taste masking, flexibility of dose titration and convenient administration. The overall aims of this research were to identify barriers for the development of acceptable medicines for children, to explore methodology for palatability and patient’s acceptability testing and to generate evidence of acceptability of flexible solid oral dosage forms. Methodological tools for the assessment of palatability and acceptability were developed and the use of such tools was explored through a series of investigations in healthy volunteers using model placebo formulations. Pharmaceutical formulation work was performed to optimise formulation design and choice of excipients, integrating manufacturability and patient’s acceptability criteria. A direct comparison between palatability and acceptability outcomes in children and adults was performed, which highlighted the value of conducting studies in adults to provide initial guidance on formulation design. Some of the key formulation factors that affect acceptability of flexible solid oral dosage forms were identified, which can be used to guide the development of more palatable and acceptable medicines. This research also evidenced methodological barriers in the assessment of palatability and patient’s acceptability which are thoroughly discussed in this thesis and will need to be overcome in the future. The knowledge generated by this research is applicable not only to the development of medicines for children, but also for other subsets of the population.
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Pham, Thu. "Design and characterisation of orally dissolving films as a potential new dosage form for paediatrics." Thesis, Aston University, 2017. http://publications.aston.ac.uk/37516/.
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Orally dissolving films (ODFs) have received much attention as potential delivery systems for oral administration of drugs to paediatric patients. With their unique properties and advantages, the technology offers improved patient compliance and wider acceptability, eliminated fear of choking, ease of administration and dosing convenience,without the requirement of water. This research focused on the formulation of ODFs with suitable physico-chemical and clinical properties as a potential dosage form for paediatric use. Initial studies focused on screening different film-forming materials used for the preparation of orally dissolving films in order to optimise and propose suitable polymers and plasticisers with a suitable manufacturing technique. Kollicoat Protect was a selected candidate for further studies, due to its excellent film forming capacity with rapid disintegration. The work also sought to improve the loading capacity, taste masking and drug content uniformity of both hydrophilic (dexchlorpheniramine malate) and hydrophobic(glipizide) drugs into ODFs, especially for poorly water soluble drugs, through complexation with cyclodextrins (CDs) and incorporation with nanoparticles. Results demonstrated that CD complexation showed improvement in the solubility profile of glipizide, whilst drug loading efficiency and drug content uniformity only improved at low doses, based on the limited cavity sizes. Nonetheless, the application of nanoparticles achieved good drug loading efficiency for glipizide at higher doses. In contrast, the loading capacity and other physico-chemical properties of dexchlorpheniramine maleateloaded films remain flexible. Further, method development to optimise the determination of disintegration time of ODFs proved that the media and media volume has no effect on disintegration time using either beaker or the texture analyser method, but the analyser method demonstrated to be more suitable for quality control setting of ODFs. Of the stability performance of ODFs, films packed with the prototype packaging remained stable over the period of time studied at both long term and accelerated conditions, which indicated their robust and clinical use through the product developmental stages.
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Dogra, Sanjeev. "A Chitosan–Polymer Hydrogel Bead System For A Metformin HCl Controlled Release Oral Dosage Form." University of Toledo Health Science Campus / OhioLINK, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=mco1303179716.
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Chaibva, Faith Anesu. "Development and assessment of an oxytocin parenteral dosage form prepared using pluronic ® F127." Thesis, Rhodes University, 2007. http://hdl.handle.net/10962/d1003225.
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Ali, Wedad Kamal. "Improving dissolution of poorly-water soluble drugs : from dosage form design to manufacture." Thesis, University of Reading, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.552989.
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Solid dispersions have been employed as a method to improve the dissolution rate and hence the bioavailability of Class 11 poorly-water soluble drugs. The objective of the thesis was to investigate, the mechanisms of dissolution enhancement of poorly- water soluble drugs by solid dispersion in hydrophilic carriers that have surface activity. Ibuprofen was used as a primary model drug; the study was then expanded to test these systems with other poorly-water soluble drugs chosen for a range of functional groups and physicochemical properties. Possible intermolecular interactions between drugs and poloxamer were investigated. Differential scanning calorimetry, Fourier transform infrared spectroscopy, and X-ray diffractometry confirmed intermolecular interaction at 2:1 ratio; this correlated with the greatest dissolution enhancement. Scanning electron microscopy showed changes in the size and habit of ibuprofen crystals in solid dispersions at various mole ratios (drug:poloxamer 407). Raman microscopy and mapping was used to investigate the distribution of drug in solid dispersions of various drug loads showing largely homogenous dispersions at 2:1 ratios and heterogeneous systems above 2:1 ratio. Several manufacturing and formulation modifications were applied to improve the dissolution and the mechanical properties of solid dispersions. These were based on the formation of nanoporous structure prior or during the dissolution process. Amongst these modified solid dispersions, those prepared by incorporation of fast dissolving sugars showed a remarkable enhancement in the dissolution rate of ibuprofen. Both modified and unmodified solid dispersions were processed into tablets and release of drug from tableted solid dispersion was investigated. Poloxamer polymeric micelles were investigated over a range of concentrations. The size and size distribution of poloxamer micelles were greatly affected by temperature, concentration and drug load. Dissolution testing revealed that the release of drug from poloxamer micelle was not significantly different to that from solid dispersion of similar drug load suggesting micelle formation from both formulations during dissolution.
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Owaisat, Suzan. "A novel oral dosage form with drug independent formulation and variable controlled release." Diss., Temple University Libraries, 2015. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/342831.
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Pharmaceutical SciencesPh.D.
A unique dosage form which uses a hydrophilic polymer was developed to provide for a predicable release of several drugs. This drug release could be optimized for controlled release using erosion. It can also be designed to release drug utilizing electrochemical processes. The accuracy of drug delivery in terms of dose and timing is of utmost importance for the patient’s health status and compliance. A well-designed drug delivery technology offers many advantages to the patient. These advantages include: reduction in dose frequency, reduction of drug side effects, reduced unwanted fluctuations in circulating drug levels, and a more uniform effect of the drug over time. The practice of drug delivery has been dramatically developed in the last decade including electronic controlled release innovative dosage forms. In this study the iontophoretic flux of ibuprofen was investigated using side- by-side diffusion cells. Iontophoresis is the process where electric current is applied to enhance transportation of drugs across the skin. The pH change was found to be an important factor in increasing the diffusion of the drug. The principle of using electric current as a driving force to control the drug release was initially demonstrated on an initial setup. Subsequently, a calcium binding polymer was the hydrogel used as a matrix to develop a new electric oral dosage form. The calcium binding polymer is produced in different forms. The production process of these forms suffers several limitations. In order to apply electric current in a practical way to the calcium binding polymer matrix a novel method was developed. The novel method also allowed for addressing the limitations related to the production process of the conventional dosage form made with this polymer. More uniform gel tablets in shape and size were produced. Different formulations were developed. Ibuprofen was the model drug initially used to investigate the factors that affected the release profiles of these tablets. A two-level, three-factor statistical design of experiments (DOE) was performed to evaluate the effect of those factors on certain responses. These responses included the release rate, time needed to release 80% of the model drug, and lag-time. A new formulation with certain adjuvants was developed. This formulation had the ability to release different kinds of drugs in a uniform release rate. A fail-safe tablet that can only release less than 20% of the drug in 24 hours was developed. The drug release was initiated only when the electric current was applied. This new electric dosage form was aimed to overcome the disadvantages related to conventional dosage forms such as the inability to supply drugs on demand.
Temple University--Theses
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Lam, Matthew. "The making of liqui-pellet and liqui-tablet, the next generation oral dosage form." Thesis, University of Sussex, 2019. http://sro.sussex.ac.uk/id/eprint/81934/.
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Ronchi, Federica. "DEVELOPMENT OF INNOVATIVE MODIFIED-RELEASE LIQUID ORAL DOSAGE FORMS." Doctoral thesis, Universite Libre de Bruxelles, 2020. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/312267.
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Modified-release oral drug delivery dosage forms are widely used in the pharmaceutical field to overcome all the potential issues imposed by the physiological variabilities of the gastrointestinal tract as well as to maintain drug concentrations within the therapeutic window. In the market, they are available only as solid dosage forms such as capsules or tablets. The development of a liquid oral dosage form with modified-release properties has been keenly awaited. This form could increase the compliance of patients with a swallowing impairment (i.e. paediatric, older or critically ill patients) and, consequently, the efficacy of the therapeutic treatment. In this study, a new technology has been developed that consists of multi-layered particles suspended extemporaneously in a syrup. Omeprazole and budesonide have been employed as model drugs. The coating procedure was optimized to obtain a yield of minimum 90% w/w and a median diameter below 500 µm. Once the final suspension is prepared extemporaneously, it presents sufficient stability to guarantee the administration of multiple doses filled into a syrup bottle and kept for a limited storage time at room temperature (e.g. up to 10 doses to be administered within 10 days).Doctorat en Sciences biomédicales et pharmaceutiques (Pharmacie)
info:eu-repo/semantics/nonPublished
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Van, der Merwe Adriana Johanna. "Development and evaluation of an oral fixed–dose triple combination dosage form for artesunate, dapsone and proguanil / van der Merwe, A.J." Thesis, North-West University, 2011. http://hdl.handle.net/10394/7579.
Full textAbstract:
Malaria is a life–threatening disease caused by Plasmodium spp and causes over one million
deaths annually. The complex life cycle of the malaria parasite offers several points of attack
for the antimalarial drugs. The rapid spread of resistance against antimalarial drugs, especially
chloroquine and pyrimethamine–sulphadoxine, emphasises the need for new alternatives or
modification of existing drugs. Artemisinin–based combination therapies (ACT’s) with different
targets prevent or delay the development of drug resistance and therefore have been adopted
as first–line therapy by all endemic countries. Proguanil–dapsone, an antifolate combination is
more active than pyrimethamine–sulphadoxine and is being considered as an alternative to
pyrimethamine–sulphadoxine. Artesunate–proguanil–dapsone is a new ACT that has wellmatched
pharmacokinetics and is relatively rapidly eliminated; therefore there is a reduced risk
of exposure to any single compound and potentially a decreasing risk of resistance. A few
studies have been done on a triple fixed–dose combination therapy for malaria treatment and
such a combination for artesunate, proguanil and dapsone are not currently investigated,
manufactured or distributed. The aim of this study was to develop a triple fixed–dose
combination for artesunate, proguanil and dapsone.
The formulation was developed in three phases; basic formulation development, employing
factorial design to obtain two possible optimised formulations and evaluating the optimised
formulations. During the formulation development the most suitable manufacturing procedure
and excipients were selected. A full 24 factorial design (four factors at two levels) was used to
obtain the optimised formulations. As end–points to identify the optimised formulations, weight
variation, friability, crushing strength and disintegration of the tablets, were used. Statistical
analysis (one way ANOVA) was used to identify optimal formulations. To identify any
interaction between the active pharmaceutical ingredients (API’s) and the API’s and excipients,
differential scanning calorimetry was done. Flow properties of the powder mixtures (of the
optimised formulations) were characterised by means of angle of repose; critical orifice diameter
(COD); bulk density and tapped density; and flow rate. Tablets of the two optimised powder
formulations were compressed. The tablets were evaluated and characterised in terms of
weight variation, friability, crushing strength, disintegration and dissolution behaviour. Initial
formulation development indicated that wet granulation was the most suitable manufacturing method. The results from the factorial design indicated that different amounts (% w/w) of the
lubricant and binder as well as two different fillers influenced the weight variation, crushing
strength and disintegration statistically significant. Two formulations containing two different
fillers (microcrystalline cellulose or Avicel® PH 101, and lactose or Granulac® 200) were found to
be within specifications and ideal for manufacturing.
Tablets prepared from the FA formulation (formulation containing Avicel® PH 101) complied with
the standards and guidelines for weight variation, friability, crushing strength and disintegration
as set by the British Pharmacopoeia (BP). Tablets had an average crushing strength of 121.56
± 0.022 N. Tablets disintegrated within 52.00 seconds and a maximum weight loss of 0.68%
occurred during the friability test. Weight variation of the tablets prepared from the FG
formulation (formulation containing Granulac® 200) complied with the standards. Average
crushing strength was 91.99 ± 6.008 N and the tablets disintegrated within 140.00 seconds.
Percentage friability (1.024%) did not comply with the guideline of a percentage friability of less
than 1%, however, no cracked or broken tablets were seen.
Dissolution showed that 98, 93 and 94% of artesunate, proguanil and dapsone were
respectively released (of the label value) within 15 minutes for the FA formulations. Release of
artesunate, proguanil and dapsone for the FG formulation was 62, 85 and 92% for the same
time period. The release of the three API’s (the FG formulation) increased to 78, 89 and 92%, respectively, after 45 minutes.Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2012.
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Buys, Gerhardus Martinus. "Formulation of a chitosan multi-unit dosage form for drug delivery to the colon / G.M. Buys." Thesis, North-West University, 2006. http://hdl.handle.net/10394/1687.
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Olivier, EI, Toit D. Du, and JH Hamman. "Development of an analytical method for the evaluation of N,N-dimethylformamide in dosage form design." Pharmazie, 2007. http://encore.tut.ac.za/iii/cpro/DigitalItemViewPage.external?sp=1000865.
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N,N-Dimethylformamide (DMF) is a well-known chemical entity that is extensively used for pharmaceutical,
biomedical and chemical applications. Previous research identified the need for the development
of an effective dosage form for the systemic delivery of DMF due to its unique antiviral properties. For
purposes of quality control and evaluation during pharmaceutical product development, development
of an analytical method was required. A gas chromatographic (GC) method was developed with a
flame-ionization detector (FID) on a carbowax packed glass column. 2-Methoxyethanol was used as
internal standard. The analytical method proved to be capable of separating DMF and 2-methoxyethanol
adequately within a relatively short runtime of 2.5 min. The analytical method described was primarily
developed for use in dissolution studies of DMF containing delivery systems. Various physicochemical
properties of candidate internal standard materials were correlated with the observed retention
times of these compounds. The best correlation (r2 ¼ 0.8077) was obtained between the boiling
point and the retention time of the compounds for the current application. The boiling point of an
internal standard candidate material may therefore be useful in predicting the retention time of that
compound under similar conditions.
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Bowles, A. F. "Development of a multiparticulate-based platform for delivering functionalised capability as an oral liquid dosage form." Thesis, University College London (University of London), 2013. http://discovery.ucl.ac.uk/1404382/.
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That ‘Children are not small adults’ is a commonly quoted adage: nowhere is this more true than in pharmaceutics. When trying to make an “age-appropriate” oral dosage form, a number of patient needs must be met including swallowability, dose-adaptability and acceptability. Acceptability may be enhanced by better tasting, non-gritty medicines: with this in mind this research sought to develop a suspension platform for functionalised multiparticulates, namely for taste-masking. The rheology of the suspending media and its effect on the suspendability of large (>100 μm) placebo particles was investigated before the influence of particle concentration, size and media viscosity of these suspensions on grittiness and acceptability was assessed in two sensory trials containing young adults. It was found that higher concentrations of hydoxypropylmethycellulose were not well tolerated due to their inherent taste and that their acceptability was improved through the addition of flavouring/sweetening agents. Statistical analysis of the results on the refined media and sensory trial showed that particle size and media viscosity had an effect on grittiness, unlike particle concentration. Microparticles of Eudragit® E (a reverse-enteric polymer marketed for taste-masking) containing quinine hydrochloride as a bitter drug were prepared by spray-drying without using organic solvents. Initial experiments resulted in many blockages of the spray dryer which were eventually rectified by increased homogenization and a fractional factorial experimental design employed to screen the influence of different levels of excipients. However, even the optimised process suffered from problems with a low feed solids concentration, low spray rate and low yield. Most particles had an aggregated morphology and the formulations which showed the lowest release in salivary pH were the most aggregated with particle sizes >1 mm. These large particles were not easy to uniformly suspend and would have required a large mass to be administered due to low drug loading which made them unsuitable for use as a uniform platform.
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Oyebola, Mosunmola Titilayo. "Investigation into the reproducibility of powder flow measurments and their relevance for pharmaceutical dosage form manufacture." Thesis, University College London (University of London), 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.415970.
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Ventura, Danielle Martins. "Desenvolvimento farmacotécnico de formulações de suspensões de hidroclorotiazida obtidas por transformação de formas farmacêuticas." Niterói, 2017. https://app.uff.br/riuff/handle/1/3268.
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As formas farmacêuticas líquidas são as mais adequadas para uso em pediatria e em pacientes que não conseguem deglutir comprimidos, pois além de apresentarem maior flexibilidade no ajuste da dose, facilitam a administração dos medicamentos. Como a maioria dos medicamentos disponíveis no mercado está na forma de comprimidos e cápsulas, o recurso utilizado no ambiente hospitalar para contornar as necessidades terapêuticas exclusivas de alguns pacientes é a transformação de formas farmacêuticas (TFF). A literatura apresenta poucos estudos relacionados à estabilidade das formulações produzidas através desta prática, fazendo com que ocorra a utilização empírica dessas formulações. O presente trabalho teve como objetivo desenvolver uma formulação de suspensão de Hidroclorotiazida (HCTZ) a partir de comprimidos de diferentes origens, através de TFF, a ser manipulada em ambiente hospitalar. Para tanto, utilizou-se uma formulação proposta por TAGLIARI (2008), estabelecida para a preparação de suspensões de HCTZ a partir insumo farmacêutico ativo, a fim de se avaliar a aplicabilidade desta formulação às suspensões produzidas por TFF. A formulação proposta tem como composição do veículo suspensor: Carboximetilcelulose sódica (CMC-Na) (0,6%), Glicerina (2%), Benzoato de sódio (0,1%) ácido cítrico e água, mostrando-se estável por mais de 120 dias. Neste trabalho, assumiu-se que as preparações decorrentes da prática de TFF são consideradas preparações extemporâneas e portanto, apresentam prazo de validade de 48 horas, sendo este o período determinado para realização dos ensaios de caracterização. Foram utilizados comprimidos de 4 fabricantes diferentes, sendo que para um deles (FA) utilizou-se comprimidos de 2 dosagens, apresentando as seguintes nomenclaturas: FA1(HCTZ 25mg), FA2 (HCTZ 50mg), FB(HCTZ 25mg), FC (HCTZ 25mg) e FD (HCTZ 50mg). Foi realizada a caracterização desses comprimidos, no qual se determinou o peso médio e o teor, segundo compêndios oficiais, e após a trituração dos mesmos, verificou-se a densidade e a granulometria dos pós obtidos. Os comprimidos de FC apresentaram teor acima do preconizado pela Farmacopeia Brasileira. Porém, optou-se por mante-los no estudo, mediante a correção da quantidade de pó a ser utilizada no preparo das suspensões. As suspensões de HCTZ a 2,5mg/mL foram preparadas utilizando CMC-Na a 0,6% (p/v) como agente suspensor. As formulações produzidas foram avaliadas quanto ao volume de sedimentação e redispersibilidade. Os resultados obtidos nestes ensaios indicaram que as suspensões não apresentavam estabilidade física apropriada, sendo necessária a realização da adequação da formulação proposta. Foram preparadas então, suspensões com veículo suspensor contendo diferentes concentrações de CMC-Na (0,2%, 0,3%, 0,4%, 0,5% e 0,6%) para todos comprimidos utilizados na primeira etapa. As preparações obtidas foram analisadas quanto ao volume de sedimentação, redispersibilidade, comportamento reológico e potencial zeta. O teste de volume de sedimentação mostrou grandes diferenças em todas as suspensões estudadas, diferindo na velocidade de sedimentação e no volume de sedimento formado, sendo estes dependentes da concentração do polímero utilizada. A redispersibilidade foi estudada em dois períodos: após 2 e 7 dias de repouso, sendo semelhantes os resultados encontrados nos dois períodos. Neste teste, os resultados apontaram grandes diferenças na redispersão das formulações, indicando que quanto maior concentração do polímero, mais tempo a preparação levou para ficar homogênea. Na análise do comportamento reológico, todas as formulações estudadas apresentaram fluxo não-newtoniano pseudoplástico, mostrando-se dependente da concentração do polímero utilizada. O potencial zeta obtido nestas preparações indicou a que as suspensões apresentaram-se floculadas. As diferenças apresentadas nos testes realizados indicaram que os diferentes excipientes presentes nas formulações dos comprimidos utilizados, interferiram na estabilidade física das preparações, não sendo possível estabelecer uma formulação a ser utilizada para todos os comprimidos, numa preparação obtida por TFF. Diante disso, foi eleita a formulação de melhor estabilidade física para cada comprimido estudado, e procedeu-se a analise do teor destas formulações. Para tanto, utilizou-se a metodologia analítica farmacopeica, que demonstrou ser especifica, linear, exata, precisa e robusta, dentro das condições experimentais estudadas. As formulações produzidas a partir de TFF apresentaram teor dentro do critério de aceitação proposto
The liquid dosage forms are suitable for use in children and in patients who can’t swallow pills, because it have greater flexibility in dose adjustment and ease the administration of medicines. Like most drugs on the market is in the form of tablets and capsules, the resource used in hospitals to circumvent the unique therapeutic needs of some patients is the transformation of pharmaceutical forms (TPF). The literature contains few studies related to the stability of the formulations produced by this practice, allowing it to empirical use of these formulations. This study aimed to develop a suspension formulation of hydrochlorothiazide (HCTZ) from tablets of different sources through TPF, to be manipulated in a hospital environment. For this purpose, we used a formulation proposed by Tagliari (2008), established for the preparation of suspensions of HCTZ from active pharmaceutical ingredient, in order to evaluate the applicability of this formulation produced by TFF. The proposed formulation has the composition of the vehicle hanger: sodium carboxymethylcellulose (CMC-Na) (0.6%), glycerin (2%), sodium benzoate (0.1%) citric acid and water, being stable for more of 120 days. In this work, it was assumed that the preparations from the practice of TFF preparations are considered untimely and therefore have shelf life of 48 hours, this being the period of time to achieve the characterization tests. The tablets were used from four different manufacturers, and for one (FA) was used two doses of pills, with the following classifications: FA1 (HCTZ 25 mg), FA2 (HCTZ 50 mg), FB (HCTZ 25 mg), FC (HCTZ 25mg) and FD (HCTZ 50 mg). We performed the characterization of these tablets, which determined the weight and content, according to official compendia, and after grinding the same, there was the density and particle size of powders obtained. FC tablets showed above the level recommended by the Brazilian Pharmacopoeia. However, it was decided to keep them in the study, by correction of the amount of powder to be used in the preparation of suspensions. Suspensions of HCTZ to 2.5 mg/mL were prepared using CMC-Na 0.6% (w/v) as an agent hanger. The formulations produced were evaluated for the amount of sedimentation and redispersibilidade. The results from these tests indicated that the suspensions had no proper physical stability, being necessary to perform the suitability of the proposed formulation. Were then prepared, with vehicle suspensions suspensor containing different concentrations of CMC-Na (0.2%, 0.3%, 0.4%, 0.5% and 0.6%) for all tablets used in the first step. The preparations obtained were analyzed for the amount of sedimentation, redispersibilidade, zeta potential and rheological behavior. The sedimentation volume test showed significant differences in all the suspensions studied, differing in sedimentation rate and volume of sediment formed, which are dependent on the concentration of the polymer used. The redispersibilidade was studied in two periods: after 2 and 7 days of rest, the results were similar in both periods. In this test, the results showed great differences in the redispersion of the formulations, indicating that the higher concentration of the polymer, the preparation took more time to be homogeneous. In the analysis of rheological behavior, all the formulations studied showed non-Newtonian pseudoplastic flow, being dependent on the concentration of the polymer used. The zeta potential obtained in these preparations indicated that the suspensions had to flocculate. The differences in the tests indicated that the different excipients present in formulations of tablets used, influenced the physical stability of the preparations, it is not possible to establish a formulation to be used for all tablets, a preparation obtained by TPF. Thereat, the better physical stability for each formulation studied was elected, and we proceeded to analyze the content of these formulations. For this purpose, we used the analytical methodology pharmacopoeia, which proved to be specific, linear, accurate, precise and robust, within the experimental conditions studied. The formulations produced from TPF content presented within the proposed acceptance criterion
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LALWANI, DARSHAN NARENDRA. "An oral dosage form of ceftriaxone sodium using enteric coated sustained release calcium alginate beads." University of Toledo Health Science Campus / OhioLINK, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=mco1430403186.
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Grout, B. F. "Novel applications of at-line near-infrared spectroscopy as process analytical technology for solid dosage form pharmaceutical analysis." Thesis, University College London (University of London), 2013. http://discovery.ucl.ac.uk/1395997/.
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The principal aim of this research was to assess at-line Near Infrared Spectroscopy (NIRS) to support Process Analytical Technology (PAT) applications within solid dosage form manufacturing. The history of PAT was traced from implementation of process analytical applications prior to the 2003 United States, Food and Drug Administration PAT initiative through to current time. The use of NIRS within the PAT context was reviewed, highlighting two areas in solid dosage manufacturing where further research of at-line NIRS is warranted; material testing and finished dosage form analysis. Novel applications of at-line NIRS were investigated and developed aligned with the PAT philosophy, to establish an innovative system of analysis that combined chemometrics and spectral analysis with statistical process control (SPC). In particular, various chemometric algorithms were explored to enable rapid monitoring of global spectral quality as well as the quality of specific critical-to-process material attributes within a SPC framework. Novel approaches to within and between batch SPC for tablet quality conformance were also developed including the adaption of distribution profile control charts typically applied to particle size measurement. These were quick to develop with greatly reduced reliance on reference analysis. It provided an opportunity for extensive process monitoring and in-depth process understanding. The work highlighted gaps in currently available chemometric and SPC capabilities within NIR instrument control software and provided insight into a new direction for NIRS analysis in the future. The new conformance methodology was demonstrated to provide business value and critical science based understanding of the pharmaceutical formulation and processes with successful application of the methodology at a commercial Pfizer facility. This methodology is in the process of rolling out worldwide. The approach was found to be approachable for plant operators through to quality analysts, and is broadly applicable with the potential to extend beyond the solid dosage form studied.
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Butler, James [Verfasser]. "The optimal use of in-vitro tools for the prediction of in-vivo oral dosage form behaviour / James Butler." Aachen : Shaker, 2012. http://d-nb.info/1069046442/34.
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Dube, Admire. "The design, preparation and evaluation of Artemisia Afra and placebos in tea bag dosage form suitable for use in clinical trials." Thesis, University of the Western Cape, 2006. http://etd.uwc.ac.za/index.php?module=etd&action=viewtitle&id=gen8Srv25Nme4_2915_1188480959.
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Artemisia Afra, a popular South African traditional herbal medicine is commonly administered as a tea infusion of the leaves. However, clinical trials proving it safety and efficacy are lacking mainly due to the absence of good quality dosage forms and credible placebos for the plant. The objectives of this study were to prepare a standardized preparation of the plant leaves and freeze-dried aqueous extract powder of the leaves, in a tea bag dosage form and to design and prepare credible placebos for these plant materials.
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Kindgen, Sarah M. [Verfasser]. "Hydrodynamics and solid dosage form disintegration/dissolution : immediate release tablets and novel in situ polyelectrolyte gastroretentive drug delivery systems / Sarah M. Kindgen." Mainz : Universitätsbibliothek der Johannes Gutenberg-Universität Mainz, 2015. http://d-nb.info/1225749581/34.
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Bredenberg, Susanne. "New Concepts in Administration of Drugs in Tablet Form : Formulation and Evaluation of a Sublingual Tablet for Rapid Absorption, and Presentation of an Individualised Dose Administration System." Doctoral thesis, Uppsala University, Department of Pharmacy, 2003. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-3433.
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This thesis presents two new concepts in oral drug administration and the results of evaluation of some relevant formulation factors.
Investigation into improving the homogeneity of mixtures for tableting indicated that it may be possible to obtain interactive dry mixtures of micronised drugs containing drug proportions as low as 0.015% w/w. By studying the relationship between disintegration time and tensile strength, it was found that the microstructure surrounding the disintegrant particles may influence the disintegration process. Therefore, avoidance of excipients which are highly deformable or very soluble in water will result in more rapid disintegration. Further, it is possible to increase the bioadhesive properties of a non-bioadhesive carrier material by forming interactive mixtures containing a fine particulate bioadhesive material.
The new sublingual tablet concept presented is based on interactive mixtures consisting of a water-soluble carrier covered with fine drug particles and a bioadhesive component. With this approach, it is possible to obtain rapid dissolution in combination with bioadhesive retention of the drug in the oral cavity. Clinical data indicate that this allows rapid sublingual absorption while simultaneously avoiding intestinal absorption.
An individualised dose administration system is also presented. This system is based on the use of standardised units (microtablets), each containing a sub-therapeutic amount of the active ingredient. The required dose is fine-tuned by electronically counting out a specific number of these units using an automatic dose dispenser. A patient handling study supported the suggestion that the dosage of some medications can be more easily and safely individualised for each patient with this method than by using traditional methods of mixing different standard tablet strengths or dividing tablets.
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Yin, Xianzhen. "Structure Pharmaceutics Based on Synchrotron Radiation X-Ray Micro- Computed Tomography: From Characterization to Evaluation and Innovation of Pharmaceutical Structures." Thesis, University of Bradford, 2016. http://hdl.handle.net/10454/17378.
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Drug delivery systems (DDS) are essentially pharmaceutical products for human
therapy, typically involving a mixture of active ingredients and excipients. Based
upon quantitative characterization of structure, the thesis introduces the concept
of classifying the architecture of DDS into four levels by their spatial scale and
the life time period. The primary level is recognised as the static structure of the
whole dosage form with a size from μm to cm with the final structure generated
by formulation design. The secondary level categorises the structures of particles
or sub-units to form a DDS with sizes from nm to mm as key units in processing
such as mixing, grinding, granulation and packing; The tertiary level represents
the dynamic structures of DDS during the drug release phase in vitro or in vivo
incorporating the structure size range from nm to mm, which undergo changes
during dissolution, swelling, erosion or diffusion. The spatial scale for the
quaternary level is defined as the meso or micro scale architecture of active and
non-active molecules within a DDS with sizes from Å to μm for the molecular
structure of drug and excipients.
Methods combining X-ray tomography, image processing, and 3D
reconstructions have been devised and evaluated to study systematically
pharmaceutical structures and correlate them with drug release kinetics of DDS.
Based on the quantitative structural information of pharmaceutical intermediates
and dosage forms, it is possible now to correlate structures with production
processing, behaviour and function, and the static and dynamic structures of DDS
with the release kinetics. Thus, a structure-guided methodology has been
established for the research of DDS.Chinese Academy of Sciences
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Meslard, Jean-Claude. "Immobilisation temporaire de medicaments par des liaisons hydrolysables sur des polymeres biocompatibles : application a l'ophtalmologie." Paris 6, 1988. http://www.theses.fr/1988PA066417.
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L'objectif est l'immobilisation reversible de medicaments (chloramphenicol, indometacine) au sein de lentilles de contact hydrophiles permettant une liberation lente et continue lors de leur adaptation sur des yeux malades
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Lee, Tak-yee. "Part 1: Computer aided dosage form design: theory and applications. Part 2: Kinetics and mechanism of captopril oxidation in aqueous solutions under controlled oxygen partial pressure /." The Ohio State University, 1986. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487266011224445.
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Pereira, Camelo Sarah Regina. "Encapsulation de molécules hydrophobes par des structures bi-gels générées par prilling : relation structure-propriétés." Thesis, Ecole nationale des Mines d'Albi-Carmaux, 2015. http://www.theses.fr/2015EMAC0002/document.
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Ce travail de thèse s’articule autour de la génération et de la caractérisation de capsules d’organo-hydrogel ou simplement bi-gels, obtenues par la technologie du prilling et destinées à la délivrance contrôlée d’un principe actif (P.A), après administration par voie orale. L’Efavirenz (EFV), un antirétroviral utilisé dans le traitement du VIH/Sida, a été le P.A utilisé comme modèle de molécule de faible solubilité dans l’eau. Il a été dissous dans l’organogel composé d’huile de tournesol et d’acide 12-hydroxystéarique (12-HSA). L’organogel a été caractérisé par sa température de transition de phase sol-gel-sol. Et la thermoréversibilité caractéristique de cet organogel n’a pas changé avec l’introduction de l’EFV. Pour la caractérisation des organogels comme véhicule de P.A, ils ont été produits à deux températures (5°C et 25 °C) et avec deux concentrations de 12-HSA (5% et 20%). Pour les essais de libération de l’EFV deux milieux de dissolution ont été utilisés (pH 1,2 et 6,8) avec et sans enzymes. Le profil de libération de l’EFV à partir de capsules bi-gels (2500 à3000 μm de diamètre) est essentiellement lié à la quantité d’organogélifiant dans le coeur, à la présence de la membrane d’alginate et à l’état physique de cette membrane (hydratée ou sèche). Une réduction de 50% a pu être observée à pH acide en présence de la membrane externe. A pH acide la libération est plus lente qu’à pH 6,8, quand la membrane perd sa fonction protectrice et le coeur organogel passe à régler la libération. Deux mécanismes de relargage sont observés : l’érosion et la diffusion, expliqués par le modèle de Korsmeyer-PeppasThis thesis focuses on the generation and characterization of organo-hydrogel capsules (bigels), manufactured by prilling technology for controlled drug delivery after oral administration. Efavirenz (EFV), an antiretroviral medications used to treat HIV/AIDS, is the active pharmaceutical ingredient (API) used as a model molecule of low solubility in water. It was dissolved in the organogel, which is compound of sunflower oil and 12-hydroxystearic acid (12-HSA). The organogel was characterized by its phase transition temperature sol-gel-sol. The typical thermoreversibility of this organogel has not changed with introduction of EFV. The organogels were produced at two temperatures (5 °C and 25 °C) and with two concentrations of 12-HSA (5% and 20%) for being characterized as an API vehicle. Two dissolution media were used with and without enzymes (pH 1.2 and 6.8), for EFV release quantification. The EFV release profile from bi-gels capsules (diameter from 2500 to 3000 μm) is essentially related to the amount of organogelator in their core, to the presence of the alginate membrane and to the state physics of this membrane (hydrated or dry). The release of EFV has reduced 50% at acid pH in the presence of the external membrane. In simulated gastric fluid, the release is slower than at pH 6.8 (simulated intestinal fluid). In the intestine, the membrane loses its protective function and the organogel’s core begins to control the release of EFV. Two release mechanisms are observed: erosion and diffusion, which can be explained by the Korsmeyer-Peppas model
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Lajoinie, Audrey. "Optimisation de la prise en charge médicamenteuse en pédiatrie : de la forme galénique à l'efficacité clinique." Thesis, Lyon, 2017. http://www.theses.fr/2017LYSE1080/document.
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L'acceptabilité de la forme orale d'un médicament est fondamentale en pédiatrie dans la mesure où elle conditionne le succès de l'administration et l'adhérence au traitement. Malgré les règlements mis en place pour favoriser le développement de médicaments adaptés à l'usage pédiatrique, le manque de données de haut niveau de preuve portant sur les avantages et les inconvénients des différentes formes orales rend difficile le choix d'une formulation adaptée à l'enfant. L'objectif de ce travail de thèse était (i) d'évaluer les avantages et les inconvénients des différentes formes pharmaceutiques orales chez l'enfant, et (ii) de proposer une méthodologie pour évaluer l'influence de la forme orale sur la balance bénéfice / risque clinique et globale (aspects économiques, pratiques et logistiques) du médicament en pédiatrie. Dans une première partie, après avoir évalué et discuté les avantages et les inconvénients des formes orales utilisées en pédiatrie au moyen d'une revue de la littérature et d'études observationnelles, nous avons proposé un protocole de méta analyse Cochrane. Un état des lieux des formes orales administrées en pédiatrie a permis d'identifier les formes potentiellement non adaptées. Dans une seconde partie, nous avons étudié la faisabilité d'une modélisation pharmacocinétique pharmacodynamique pour évaluer l'influence de la forme orale sur la balance bénéfice / risque appliquée à l'acide valproïque (VPA). Les données de routine (concentrations résiduelles) ne permettant pas de construire un modèle pharmacocinétique afin d'évaluer l'influence des formes orales sur le profil de concentration du VPA, nous avons conçu un protocole d'essai clinique randomisé visant à évaluer l'acceptabilité et l'observance des formes orales du VPA, et à collecter les données pharmacocinétiques et pharmacodynamiques nécessaires à la construction du modèle pour l'évaluation de la balance bénéfice / risque du VPA. L'analyse des difficultés liées à l'évaluation de l'acceptabilité chez l'enfant et des limites à l'utilisation des données de routine tout au long de ce travail de thèse a été déterminante pour la conception de ce protocoleThe acceptability of a medicine oral dosage form is fundamental in paediatrics as it determines the success of the administration and treatment adherence. Despite regulations implemented to stimulate the development of appropriate medicine for the paediatric population, the lack of high level proof data concerning advantages and limits of the different oral dosage forms makes difficult the choice of a suitable paediatric dosage form. The objectives of this thesis were (i) to assess advantages and limits of the different available oral dosage forms in children, and (ii) to propose a method to evaluate the influence of the oral dosage form on both clinical and overall (i.e. including economic, practical and logistical aspects) risk/benefit balance in paediatrics. First, we assessed and discussed advantages and limits of oral dosage forms used in children based on a literature review of expert’s opinion and available studies, and conducting observational studies in our paediatric hospital. We finally designed a Cochrane meta-analysis protocol. In addition, the analysis of oral dosage forms currently administered in our paediatric hospital allowed to identify those not suitable for children. Secondly, we studied the feasibility of a pharmacokinetic pharmacodynamic model to assess the influence of the oral dosage form on the valproate (VPA) risk/benefit balance. Routine data (serum trough concentrations) did not allow to simulate the influence of the oral dosage form on the VPA serum level profile. Thus, we designed a protocol of a randomised controlled trial aiming to assess the acceptability and adherence of the different VPA oral dosage forms, and to collect VPA pharmacodynamic and pharmacokinetic data needed for the building of the model to evaluate the influence of the oral dosage form on the risk/benefit balance. The difficulties related to medicine acceptability measurement in children and limits we encountered were decisive for the design of such protocol
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LUTZ, OLIVIER. "Activite lipolytique tissulaire et post-heparine sur les emulsions parenterales." Université Louis Pasteur (Strasbourg) (1971-2008), 1989. http://www.theses.fr/1989STR13038.
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L'hydrolyse des lipides d'emulsion parenterale par la lipoproteine lipase et la lipase hepatique. Elle depend du rapport phospholipide**((pl))/triacylglycerol**((tg)). Un exces de pol par rapport aux tg entraine la formation de liposomes qui sont des inhibiteurs de la lipase. La longueur des chaines des tg ont aussi une influence sur l'epuration des emulsions
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Ibrahim, Mohamed Asim Y. "Co-processing of drugs and co-crystal formers and its effect on pharmaceutical dosage-form performance. Co-crystallization of urea/ 2-methoxybenzamide, caffeine/ malonic acid, caffeine/ oxalic acid and theophylline/ malonic acid systems: Solid-state characterization including imaging, thermal, X-ray and Raman spectroscopic techniques with subsequent evaluation of tableting behaviour." Thesis, University of Bradford, 2008. http://hdl.handle.net/10454/12760.
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This dissertation has focused on the solid-state characterization of different co-crystal system as well as the effect of co-crystallization of these systems on pharmaceutical dosage form performance. Urea/ 2-MB, caffeine/ malonic acid, caffeine/ oxalic acid and theophylline/ malonic acid co-crystals were prepared using co-grinding- and co-precipitation techniques. In addition, the synthesis of co-crystals through two novel methods has been demonstrated. This includes compaction and convection mixing. The solid-state characterization of the co-crystals has been carried out using XRPD, Raman spectroscopy, DSC, TGA, hot-stage microscopy and SEM. After preparation of co-crystals, tablets have been produced from co-ground-, co-precipitated-, and physical mixtures using Compaction Studies Press (Kaleva), and the data were recorded to compare between the different mixtures, regarding compactibilty, compressibility and deformational properties. The DSC results showed that the physical mixtures of all systems, formed co-crystals during heating process. For systems of urea/ 2-MB, caffeine/ malonic acid and theophylline/ malonic acid, the co-ground mixture produced tablets with higher tensile strength compared with either co-precipitated or physical mixture. However, for caffeine/ oxalic acid system, the tensile strengths of compacts produced from the physical mixture were greater than those obtained from either co-ground or co-precipitated mixtures. The Heckel data suggested that urea/ 2-MB, caffeine/ malonic acid and theophylline/ malonic acid systems are Type 1 materials, as an extensive linearity during compression was indicative of a plastic deformation mechanism, while the caffeine/ oxalic acid system was Type 2 materials. However, the co-precipitated mixture of urea/ 2-MB system was the least compressible, as it possessed the greatest value of yield pressure (85 MPa) and the highest elastic recovery (7.42%). The co-precipitated mixture of both of caffeine/ malonic acid and theophylline/ malonic acid systems was the most compressible with small yield pressure values of (44 & 80 MPa) and elastic recovery of (7.2% & 6.56%), respectively. The co-ground mixture of caffeine/ oxalic acid possessed the highest value of yield pressure (166 MPa) and thus the lowest compressibility among other mixtures. Furthermore, the addition of microcrystalline cellulose and α-lactose monohydrate has affected the crystallinity as well as the tableting properties of the co-crystals. After the addition of excipients, the tensile strength of compacts was about 2 times higher than any other mixture. Finally, urea/ 2-MB and caffeine/ malonic acid co-crystals were successfully synthesized through convection mixing and compaction.Islamic University of Omdurman and the Ministry of Higher Education in Sudan
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Ibrahim, Mohamed Asim Yousif. "Co-processing of drugs and co-crystal formers and its effect on pharmaceutical dosage-form performance : co-crystallization of urea/2-methoxybenzamide, caffeine/malonic acid, caffeine/oxalic acid and theophylline/malonic acid systems : solid-state characterization including imaging, thermal, X-ray and Raman spectroscopic techniques with subsequent evaluation of tableting behaviour." Thesis, University of Bradford, 2008. http://hdl.handle.net/10454/12760.
Full textAbstract:
This dissertation has focused on the solid-state characterization of different co-crystal system as well as the effect of co-crystallization of these systems on pharmaceutical dosage form performance. Urea/ 2-MB, caffeine/ malonic acid, caffeine/ oxalic acid and theophylline/ malonic acid co-crystals were prepared using co-grinding- and co-precipitation techniques. In addition, the synthesis of co-crystals through two novel methods has been demonstrated. This includes compaction and convection mixing. The solid-state characterization of the co-crystals has been carried out using XRPD, Raman spectroscopy, DSC, TGA, hot-stage microscopy and SEM. After preparation of co-crystals, tablets have been produced from co-ground-, co-precipitated-, and physical mixtures using Compaction Studies Press (Kaleva), and the data were recorded to compare between the different mixtures, regarding compactibilty, compressibility and deformational properties. The DSC results showed that the physical mixtures of all systems, formed co-crystals during heating process. For systems of urea/ 2-MB, caffeine/ malonic acid and theophylline/ malonic acid, the co-ground mixture produced tablets with higher tensile strength compared with either co-precipitated or physical mixture. However, for caffeine/ oxalic acid system, the tensile strengths of compacts produced from the physical mixture were greater than those obtained from either co-ground or co-precipitated mixtures. The Heckel data suggested that urea/ 2-MB, caffeine/ malonic acid and theophylline/ malonic acid systems are Type 1 materials, as an extensive linearity during compression was indicative of a plastic deformation mechanism, while the caffeine/ oxalic acid system was Type 2 materials. However, the co-precipitated mixture of urea/ 2-MB system was the least compressible, as it possessed the greatest value of yield pressure (85 MPa) and the highest elastic recovery (7.42%). The co-precipitated mixture of both of caffeine/ malonic acid and theophylline/ malonic acid systems was the most compressible with small yield pressure values of (44 & 80 MPa) and elastic recovery of (7.2% & 6.56%), respectively. The co-ground mixture of caffeine/ oxalic acid possessed the highest value of yield pressure (166 MPa) and thus the lowest compressibility among other mixtures. Furthermore, the addition of microcrystalline cellulose and α-lactose monohydrate has affected the crystallinity as well as the tableting properties of the co-crystals. After the addition of excipients, the tensile strength of compacts was about 2 times higher than any other mixture. Finally, urea/ 2-MB and caffeine/ malonic acid co-crystals were successfully synthesized through convection mixing and compaction.
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Pavurala, Naresh. "Oral Drug Delivery -- Molecular Design and Transport Modeling." Diss., Virginia Tech, 2013. http://hdl.handle.net/10919/53505.
Full textAbstract:
One of the major challenges faced by the pharmaceutical industry is to accelerate the product innovation process and reduce the time-to-market for new drug developments. This involves billions of dollars of investment due to the large amount of experimentation and validation processes involved. A computational modeling approach, which could explore the design space rapidly, reduce uncertainty and make better, faster and safer decisions, fits into the overall goal and complements the product development process. Our research focuses on the early preclinical stage of the drug development process involving lead selection, optimization and candidate identification steps. Our work helps in screening the most favorable candidates based on the biopharmaceutical and pharmacokinetic properties. This helps in precipitating early development failures in the early drug discovery and candidate selection processes and reduces the rate of late-stage failures, which is more expensive.
In our research, we successfully integrated two well-known models, namely the drug release model (dissolution model) with a drug transport model (compartmental absorption and transit (CAT) model) to predict the release, distribution, absorption and elimination of an oral drug through the gastrointestinal (GI) tract of the human body. In the CAT model, the GI tract is envisioned as a series of compartments, where each compartment is assumed to be a continuous stirred tank reactor (CSTR). We coupled the drug release model in the form of partial differential equations (PDE's) with the CAT model in the form of ordinary differential equations (ODE's). The developed model can also be used to design the drug tablet for target pharmacokinetic characteristics. The advantage of the suggested approach is that it includes the mechanism of drug release and also the properties of the polymer carrier into the model. The model is flexible and can be adapted based on the requirements of the clients. Through this model, we were also able to avoid depending on commercially available software which are very expensive.
In the drug discovery and development process, the tablet formulation (oral drug delivery) is an important step. The tablet consists of active pharmaceutical ingredient (API), excipients and polymer. A controlled release of drug from this tablet usually involves swelling of the polymer, forming a gel layer and diffusion of drug through the gel layer into the body. The polymer is mainly responsible for controlling the release rate (of the drug from the tablet), which would lead to a desired therapeutic effect on the body.
In our research, we also developed a molecular design strategy for generating molecular structures of polymer candidates with desired properties. Structure-property relationships and group contributions are used to estimate the polymer properties based on the polymer molecular structure, along with a computer aided technique to generate molecular structures of polymers having desired properties. In greater detail, we utilized group contribution models to estimate several desired polymer properties such as grass transition temperature (Tg), density (ρ) and linear expansion coefficient (α). We subsequently solved an optimization model, which generated molecular structures of polymers with desired property values. Some examples of new polymer repeat units are - [CONHCH₂ - CH₂NHCO]n -, - [CHOH - COO]n -. These repeat-units could potentially lead to novel polymers with interesting characteristics; a polymer chemist could further investigate these. We recognize the need to develop group contribution models for other polymer properties such as porosity of the polymer and diffusion coefficients of water and drug in the polymer, which are not currently available in literature.
The geometric characteristics and the make-up of the drug tablet have a large impact on the drug release profile in the GI tract. We are exploring the concept of tablet customization, namely designing the dosage form of the tablet based on a desired release profile. We proposed tablet configurations which could lead to desired release profiles such as constant or zero-order release, Gaussian release and pulsatile release. We expect our work to aid in the product innovation process.Ph. D.
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Velásquez, Armijo Cristián Jesús. "Aplicação de métodos termo-analíticos e espectroscóspicos na avaliação do comportamento do fármaco isoniazida frente a adjuvantes tecnológicos." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2003. http://hdl.handle.net/10183/144233.
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Os métodos termo-analíticos são ferramentas úteis na avaliação da compatibilidade entre fármacos e adjuvantes, com destaque à calorimetria exploratória diferencial. Neste trabalho foram avaliados a compatibilidade e o comportamento térmico entre a isoniazida e adjuvantes tecnológicos primários usualmente empregados em formas farmacêuticas sólidas. A compatibilidade foi examinada por meio da preparação de misturas físicas binárias do tipo fármaco/adjuvante. Foi investigada também a influência da granulação por via úmida e do processo de compactação para as misturas de isoniazida e adjuvantes com função de material de enchimento e carga e deslizante. A isoniazida apresentou um comportamento térmico não encontrado na literatura. Os adjuvantes avaliados foram: ácido esteárico, amido, celulose microcristalina, crospovidona, croscarmelose sódica, dióxido de silício coloidal estearato de magnésio, glicolato de amido sódico, hipromelose, lactose, manitol, polidona e talco. Para as misturas físicas, a maioria dos adjuvantes mostrou-se compatível com o fármaco em questão. Foram verificadas interações com o ácido esteárico, o glicolato de amido sódico, a lactose, o manitol e a povidona. A isoniazida mostrou a formação de uma mistura eutética com o manitol e de interação química com a lactose. A agregação por via úmida e o processo de compactação não mostraram influências adicionais na compatibilidade das misturas avaliadas. Os resultados observados foram confirmados por métodos não-térmicos como difratometria de raios X, espectroscopia de infravermelho e ressonância nuclear magnética.Thermo-analytical methods, and specially Differential Scanning Calorimetry, are useful support for the evaluation of compatibility between drug substances and pharmaceutical excipients. In this work were studied the compatibility and the thermal behavior of isoniazid and pharmaceutical excipients, commonly used for the formulation of solid dosage forms. Colloidal silicon dioxide, corn starch, crospovidone, hypromellose, lactose, magnesium stearate, mannitol, microcrystalline cellulose, povidone, sodium croscarmellose, sodium starch glycolate, stearic acid and talc were the excipients employed in these experiments. The compatibility was analyzed testing binary physical drug/excipient admixtures. The effect of wet granulation and compression was also investigated, in this case especially between isoniazid, fillers and lubricant. For almost all excipients no incompatibilities with isoniazid were observed. Interactions were detected when the drug substance was added to stearic acid, sodium starch glycolate, lactose, mannitol and povidone. Isoniazid formed a euthetic mixture with mannitol, whereas a possible chemical reaction occurred between isoniazid and lactose. Wet granulation and compaction of the tested admixtures did not affect the results observed above. These observations were confirmed by non-thermal techniques, such as X-Ray diffractometry, infrared spectroscopy and nuclear magnetic resonance.
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Sogias, Ioannis Andrea. "Mucoadhesion of chitosan and derivatives : from mechanism to dosage form design : understanding of chitosan solubility parameters, interactions with mucosal membranes and BCS class II drugs in formulations, targeting enhanced permeation and increased bioavailability of poorly absorbable drugs." Thesis, University of Reading, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.499371.
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Chitosan is a natural polysaccharide produced commercially from chitin by partial deacetylation. It consists of glucosamine and Al-acetyl glucosamine units chained through glycosidic bonds. Due to the biocompatible and mucoadhesive profile it presents, it has attracted considerable attention for potential uses in pharmaceutics. However, the limited solubility of chitosan only in acidic solutions constrains some of its possible uses in biological applications. Thus, the synthesis of chitosan derivatives with broader solubility and increased functionality has been considered as a strategy to extend chitosan uses.
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Grossová, Marie. "Tvorba biofilmu u probiotických bakterií a jejich zpracování do pevné lékové formy." Doctoral thesis, Vysoké učení technické v Brně. Fakulta chemická, 2016. http://www.nusl.cz/ntk/nusl-263349.
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The aim of present work is cultivation of probiotic bacteria L. acidophilus, B. breve and B. longum in such a way that the culture forms cells clusters or comprehensive biofilm on the variety of free carriers. Biofilm formation of L. acidophilus on the silica from point of view bile and acid tolerance in gastrointestinal tract was studied. While the number of living cells in planktonic form (planktonic form) at pH 1 fell by 30 %, the viability of the biofilm cells was maintained to 90 % under the same environmental conditions. The biofilm culture showed also the protection against environment contained bile. Furthermore, the possibilities of drying procedures of biofilm cultures used as commercial technologies in pharmaceutical industry were studied. The comparison of freeze-drying and fluidization bed drying showed, that freeze-drying is more suitable method, which is able to achieve higher amount of viable cells after drying than fluidization bed drying. The effectivity of freeze-drying method is dependent on the selection of suitable cryprotective medium. In this case, about 90 % higher viability after freeze drying was achieved in comparison with fluidization bed drying. Finally, the industrial processing of probiotic strains into the solid dosage form was studied. Tablets should be produced at hardness between 70 and 90 N and water activity of tablet mixture can be maintained below 0.3. Consequently, the drying step of the tablets in a hermetically closed space with at least 10 % of silica gel must be ensured. Thereafter, the tablets contain (5.4 ± 0.7)109 viable cells after 6 months of drying process. Capsule production technology has no significant effect on the cell‘s viability during production. The triplex blistering foil for primary blistering of probiotic capsules was chosen. The triplex foil, which has low values of water vapour transition rate (0.07 g H2O / (m2 × day) and oxygen transition rate (0.01 cm3/m2 × day), was chosen. Other studied blistering foils commonly used in the pharmaceutical industry are not suitable for long storage of solid dosage forms contained probiotics.
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Berrabah, Mohammed. "Etude analytique de nanocapsules renfermant des substances de nature hydrophile. Influence de la vectorisation sur le métabolisme." Rouen, 1995. http://www.theses.fr/1995ROUES008.
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Les nouvelles formes galéniques permettant la vectorisation des principes actifs à l'état de suspension de nanocapsules peuvent entraîner des modifications du métabolisme des molécules ainsi administrées. Les nanocapsules étudiées ici sont constituées d'une paroi de polycaprolactone renfermant le benzoate de benzyle dans lequel est dissous le principe actif. Un contrôle analytique par CPG-SM couplée a été mis au point et validé. Il permet grâce à une méthode d'extraction différentielle, d'identifier le principe actif resté en solution, celui qui est encapsulé et celui qui se trouve plus au moins lié à la paroi de la nanocapsule. Après traitement de rats par des suspensions de nanocapsules et recueil des urines et fèces, les métabolites excrétés sont identifiés et dosés par CPG-SM
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Star, Kristina. "Safety of Medication in Paediatrics." Doctoral thesis, Uppsala universitet, Institutionen för folkhälso- och vårdvetenskap, 2013. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-197323.
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Background: In paediatrics, the limited documentation to guide medication, the lack of suitable dosage forms, and the continuous development in childhood present a scenario where safety of medication is a particular challenge. Aim: To explore reported adverse drug reactions (ADRs) and the challenges in prescribing and administering medicines in paediatrics, in order to identify and suggest areas needing international surveillance within medication safety and improvement in the clinical setting. Methods: Four exploratory studies were conducted. Worldwide reporting of suspected ADRs (individual case safety reports, ICSR) with ages 0-17 years were examined overall. Twenty published case reports and ICSRs for adolescents, who developed a rare and incompletely documented ADR (rhabdomyolysis) during antipsychotic medicine use, were analysed in-depth. Prescribed doses of anti-inflammatory medicines were studied in a UK electronic health record database. Transcribed focus group interviews with 20 registered nurses from four paediatric wards in Sweden were analysed for factors that may promote or hinder safe medication practices. Descriptive statistics, multiple regression, and content analyses were used. Results: Although, skin reactions and anti-infective medicines were most frequently reported, and more reported in paediatric patients than in adults, medication errors and adverse reactions related to psychostimulant medicines were reported with increased frequency during 2005 to February 2010. The in-depth case analysis emphasised the need for increased vigilance following changes in patients’ medicine regimens, and indicated that ICSRs could contribute with clinically valuable information. Prescribed dose variations were associated with type of dosage form. Tablets and capsules were prescribed with a higher dose than liquid dosage forms. Six themes emerged from the interviews: preparation and administration was complex; medication errors caused considerable psychological burden; support from nurse colleagues was highly valued; unfamiliar medication was challenging; clear dose instructions were important; nurses handling medications needed to be accorded higher priority. Conclusions: Age-specific screening of ICSRs and the use of ICSRs to enhance knowledge of ADRs and medication errors need to be developed. Access to age-appropriate dosage forms is important when prescribing medicines to children. To improve medication safety practices in paediatric care, interdisciplinary collaborations across hospitals on national or even global levels are needed.
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Bakhouya, Abderrahmane. "Etude du processus de libération des principes actifs à partir de formes galéniques lipidiques à matrice de gélucire : modélisation de la pénétration tissulaire de la ciprofloxacine." Saint-Etienne, 1996. http://www.theses.fr/1996STET4013.
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Les formes galéniques matricielles, à matrice lipidique tels que les gélucires, permettent une libération contrôlée du principe actif. Ces matrices peuvent subir une érosion plus ou moins prononcée selon la nature de l'excipient. Lorsque le gélucire est hydrophile, le processus de libération s'effectue par érosion de la forme galénique. Avec un gélucire lipophile, le processus de libération est contrôlé par diffusion. Pour simuler le contrôle de la libération par érosion dans l'organisme, nous avons construit un modèle numérique qui tient compte de tous les facteurs ; notamment, les trois stades : libération, absorption et élimination. Nous avons considéré les cinétiques de libération de la ciprofloxacine à partir de deux formes galéniques : avec libération immédiate et avec libération contrôlée par érosion. Nous avons construit, également, un autre modèle numérique dans le but de modéliser le transport de la ciprofloxacine, à travers le tissu, du compartiment plasmatique jusqu'au blister fluid aussi bien pour la voie orale que pour l'infusion intraveineuse. Ce transport est régi par diffusion fickienne
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Monville, Daniel. "Etude de procédés de séparation par cristallisation de matériaux d'interêt pharmaceutique relevant du polymorphisme cristallin." Rouen, 1989. http://www.theses.fr/1989ROUES011.
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Shiko, Gentiana. "Quantitative and non-invasive studies of the dissolution behaviour of solid state pharmaceutics." Thesis, University of Cambridge, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.610272.
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Jaganath, Nelesh. "The application of rheological techniques in the characterization of semisolids in the pharmaceutical industry." Thesis, Nelson Mandela Metropolitan University, 2004. http://hdl.handle.net/10948/380.
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Rheological characterization of pharmaceutical semisolids is of importance as it provides fundamental information required for the assessment of some of the final properties of a product such as viscosity, elasticity, quality and storage stability. The effect of formulation variables on product characteristics such as consistency and correlation of consumer evaluation of consistency can also be attained. (Ramachandran et al., 1999) This study focussed on using rheological techniques to fully characterize the properties of various semisolid formulations being developed or produced at a South African-based generic pharmaceutical company. Various tests were employed to characterize the semisolid dosage forms (creams and ointments), including continuous shear tests such as flow and viscosity curves and yield point measurements, oscillatory tests such as amplitude and frequency sweeps, as well as step and temperature ramp tests. A method to determine justifiable and meaningful viscosity specifications was developed, where excellent reproducibility of results were obtained when compared to the single-point viscosity determinations usually used. An evaluation as to whether rheology can be utilized as an assessment tool for product stability revealed varying results, with the oscillation-frequency sweep test displaying modest predictive capabilities. Observable differences in rheological character were found when evaluating ointment formulations exhibiting deviating quality characteristics. When analysing the effect of varying processing parameters, namely, cooling rate and mixing speed, during the manufacture of a cream, statistically significant rheological differences were obtained, while a thorough characterization of a scale-up procedure was also achieved upon analysis of various rheological properties.
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Le, Roux Jacques. "The analysis of radiation-induced micronuclei in peripheral blood lymphocytes for purpose of biological dosimetry." Master's thesis, University of Cape Town, 1995. http://hdl.handle.net/11427/27038.
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In the investigation of radiation accidents, it is of great importance to estimate the dose absorbed by exposed persons in order to plan their therapy. Although occasionally in these situations physical dose measurements are possible, most often biological methods are required for dose estimation. The aim of this investigation was to assess the suitability of the cytokinesis blocked (CB) micronucleus assay as a biodosimetric method using lymphocytes irradiated in vivo. The approach adopted to achieve this was to estimate whole body doses by relating micronuclei yields in patients undergoing radiotherapy treatment with an in vitro radiation dose-response curve. These biologically derived estimates were then compared with the corresponding doses obtained by physical measurement and calculation. As a first approach a study was performed of the in vitro dose-response of gamma-ray induced micronuclei following cytokinesis-block in the lymphocytes of peripheral blood samples obtained from 4 healthy donors. The results indicated that the distribution of the induced micronuclei were overdispersed. Furthermore, a linear dose-response relationship was established when a curve was fitted to the data by an iteratively reweighted least squares method. By means of an analysis of covariance it was demonstrated that this result is in agreement with the dose-response relationships found by various other workers (Fenech et al., 1985; Fenech et al., 1986; Fenech et al., 1989; Balasem et al., 1992, and Slabbert, 1993). To assess the suitability and accuracy of dose assessment using the CB micronucleus assay for in vivo exposure of lymphocytes, blood samples obtained from 8 patients undergoing radiotherapy before, during and after treatment were examined. The physical doses of these patients were determined according to conventional radiation treatment plans and cumulative dose-volume histograms. The dose-volume histograms permitted calculation of integral doses and subsequently the estimate of equivalent whole-body doses. The results of the CB micronucleus assay applied to peripheral blood lymphocytes of 6 patients undergoing fractionated partial-body irradiation showed a dose-related increase in micronucleus frequency in each of the patients studied. This demonstrated that micronuclei analysis may serve as a quantitative biological measure of such exposures. The pooled data of these patients compared to the pooled data of the healthy donors show that there was no statistically significant difference between in vitro and in vivo results, however a slightly lower induced micronuclei frequency was observed after in vivo exposure. When the biological dose estimates for equivalent whole-body doses obtained from the in vitro dose response curve were compared with calculated physical doses, it was found that: biologically estimated dose = 0.936 physical dose. However, there was inadequate statistical evidence to discard the hypothesis that the gradient of the equation was equal to one. Therefore, the analysis of micronuclei induced in lymphocytes in vivo yields highly quantitative information on the equivalent whole-body dose. The negative binomial method was used for analysing the micronucleus data from two patients who received single, relatively larger tumour doses of 10 Gy each, with the objective to obtain estimates of the exposed body fraction and the dose to this fraction. The dose estimates to the irradiated volume were found to be within 30% of the physical tumour dose. The irradiated volume estimates seemed to be higher than the physically calculated volumes but by discarding the correction for the loss of cells due to interphase death the agreement was good between the physically and biologically determined integral doses. This study has revealed that the CB micronucleus assay appears to offer a reliable, consistent and relatively rapid biological method of whole body dose estimation. It is recognised that further corroborative work using the techniques described in this thesis is required for estimating localized exposure.
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Muschert, Susanne. "Polymeric coatings for solid dosage forms : characterization and optimization." Lille 2, 2008. http://www.theses.fr/2008LIL2S023.
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Les dispersions aqueuses de polymère sont couramment utilisées dans l'industrie pharmaceutique pour pelliculer les formes galéniques destinées à la voie orale et permettre une libération contrôlée du principe actif. Il est nécessaire de faire attention à la stabilité à long terme des films au cours du stockage et d'éviter une diminution des taux de principe actif libéré par continuation de la coalescence des particules de polymère. L'idée de ce travail était d'ajouter un second composant approprié aux dispersions aqueuses d'éthyle cellulose afin d'améliorer la formation du film et la stabilité à long terme et d'ajuster facilement les cinétiques de libération désirées. Les objectifs de cette étude sont : (i) de préparer et de caractériser en détail différents types de formes solides pelliculées ainsi que des films libres polymériques de composition identique aux pelliculages, (ii) de mieux comprendre les mécanismes de libération sous-jacents aux différentes formes solides pelliculées avec les dispersions aqueuses d'éthyle cellulose (EC) additionnées de petites quantités d'un second composant, et (iii) de proposer un moyen facile pour obtenir les cinétiques de libérations souhaitées et restant stables à long terme pour différents types de principes actifs et de noyaux de départ. Différents types de noyaux de départ ont été étudiés : (i) des noyaux matriciels de principe actif avec un haute teneur en principe actif ; (ii) des noyaux de sucre montés avec du principe actif, qui peuvent générer une pression hydrostatique significative à l'intérieur du système une fois en contact avec des milieux aqueux ; (iii) des noyaux de cellulose microcristalline (MCC) (un matériau inerte) montés avec du principe actif, et (iv) des noyaux de sucre pelliculés avec de l'EC et montés ensuite avec du principe actif. Différents types de principe actif de différents solubilités aqueuses ont été étudiés : la théophylline, le paracétamol, le succinate de métoprolol et le chlorhydrate de diltiazem. Ces derniers ont été soit montés sur des noyaux de sucre, de MCC et de sucre pelliculés avec de l'EC, soit inclus dans des noyaux matriciels à différentes teneurs. Pour maîtriser la libération du principe actif à partir de minigranules pelliculés avec de l'EC, des polymères hydrophiles tels que l'alginate de propylène glycol, le -carraghénane et le copolymère d'acide polyvinylique et de polyéthylène glycol ont été ajoutés. Tous ont montrés une bonne compatibilité avec la dispersion aqueuse d'EC ; Aquacoat ECD 30. Les minigranules ont été pelliculés en lit d'air fluidisé, l'Aquacoat ECD étant plastifié avec 25 % m/m (basé sur le poids sec du polymère) de triéthyle citrate ou de dibutyl sébaçate. Après pelliculage, les minigranules sont soumis a un traitement thermique à différents temps, températures, et humidités relatives afin d'assurer une formation complète du film et d'obtenir une stabilité à long terme sous des conditions ambiantes ainsi que des conditions stress (suivant les recommandations ICH). Les cinétiques de libération sont réalisées dans un appareil à palettes dans des milieux simulant le contenu de l'estomac et de l'intestin grêle à température corporelle. Le mélange de la dispersion aqueuse d'EC avec les différents types de polymère hydrophile permet de fournir des cinétiques de libération contrôlées avec des conditions de pelliculage et de traitement thermique appropriés, et ce quelque soit le type de principe actif et de noyau de départ. Des cinétiques de libération d'ordre zéro ont notamment pu être obtenus dans le cas de matrices de théophylline pelliculés avec un mélange d'EC: copolymère de PVA-PEG à un ratio de 85:15. L'ajout d'alginate de propylène glycol conduit à des profils de libération du principe actif pH-dépendant. Ceci peut-être très utile pour compenser la diminution de solubilité pH-dépendante de bases faibles le long du tractus gastro-intestinal. Des profils de libération stables à long terme peuvent être obtenus avec des conditions de traitement thermique appropriées. Les mécanismes de libération sous-jacents ont pu être élucidés en utilisant des solutions adéquates de la seconde loi de diffusion de Fick considérant les conditions respectives initiales et de « boundary ». De fins films polymériques ont été caractérisés part rapport à leur prise en eau et perte de masse sous exposition à différents milieux de libération et ont été utilisés pour déterminer le coefficient de diffusion apparent. La pression osmotique du milieu de libération a été variée afin d'évaluer l'impact de plus faible pressions osmotiques entre l'intérieur et l'extérieur des minigranules. Le gonflement du système a été également suivi au cours du temps sous ces conditions. Les cinétiques de libération à partir de minigranules individuels ont été menées et comparées à la libération d'un ensemble de minigranules. Le diamètre des minigranules restait environ constant au cours des 8 h d'observation, et ce quelque soit le type de noyau de départ. La pénétration continue de l'eau au sein des minigranules devrait générer une augmentation de la pression hydrostatique dans le système. Ceci pourrait alors conduire à une augmentation continue du diamètre des minigranules jusqu'à ce qu'une certaine valeur critique soit atteinte où la formation de fissures dans le pelliculage survient et le liquide interne est expulsé du système et le diamètre du minigranule diminue soudainement. On notera que ce type de comportement n'a pas été observé. Les cinétiques à partir des minigranules individuels étaient très similaires à l'ensemble de minigranules, indépendamment du type de noyau de départ et de milieu de libération. Ceci peut ne pas être nécessairement le cas, la cinétique finale observée peut être la somme de profils de libération de minigranules individuels très différents. Ainsi, il semble n'y avoir qu'un mécanisme de libération uniforme et la formation de fissures au cours du temps est improbable avec les systèmes étudiés. Cette hypothèse a été confortée par des images de microscopie électronique à balayage montrant des surfaces de minigranules lisses après exposition aux milieux de libération. La modélisation mathématique des cinétiques de libération à partir de fins films libres ainsi qu'à partir de minigranules pelliculés a révélé que les cinétiques de libération sont contrôlées par diffusion à travers une membrane polymérique intacte, ce qui est en bonne concordance avec les résultats expérimentaux. L'étape de traitement thermique nécessaire à la formation de pelliculages stables à long terme a pu être minimisée pour les différents types de système, contenant des principes actifs peu et très solubles et pour différents types de noyaux. L'addition de petites quantités d'un polymère hydrophile approprié à la dispersion aqueuse d'EC est un outil très efficace pour obtenir aisément les cinétiques de libération désirées et restant stables au cours du stockage et ce, même dans des conditions stress
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Walbrugh, Lushane. "Amitraz Solid Dosage Form." Diss., 2006. http://hdl.handle.net/2263/27430.
Full textAbstract:
This study considered the use of urea eutectics as fast release solid dosage carrier forms for the acaricide N-methylbis (2,4-xylyliminomethyl) methylamine (AmitrazTM). Wettol D2 and Arkopal N090 were chosen as the wetting agent and dispersants respectively. Their optimum levels were determined as the surfactant concentrations that yielded a minimum in the dispersion viscosity of a concentrated (30% m/m) Amitraz suspension. The optimum dosage levels were found to be ca. 2% Arkopal N090 and ca. 1% Wettol D2. Eutectic phase diagrams were obtained using the melting-cooling method. The components were ground together into a fine powder and heated in a glass tube immersed in a silicon oil bath. The liquid was allowed to cool down and solidify at ambient conditions. The time-dependant temperature change of the sample was tracked with a thermocouple. The data was captured in real time on a personal computer and analysed using an Excel spreadsheet programme. The melt-cast method was used to prepare eutectic mixtures. They were characterised using DSC, DTA, XRD and Light Microscopy. The XRD peaks showed the presence of the two separate crystal structures for the eutectic mixture constituents. The urea – CaBr2.2H2O combination was initially considered as carrier for Amitraz. However, this eutectic system was found to be too hygroscopic. Small additions of PEG 6000 improved the tablet strength but decreased the dissolution rate. Urea and acetamide formed a eutectic at ± 46oC with a composition of ca. 40 % m/m urea. Unfortunately acetamide is a suspected carcinogen. Therefore the urea - 1,3-dimethylurea was selected as Amitraz carrier system instead. The eutectic mixture comprised 40% m/m urea and 60% m/m 1,3-dimethylurea, which melt at ± 56oC. The melt-press method was used to prepare Amitraz containing pellets measuring 5 mm thick and 33 mm ö and weighing about 5,0 g. It was possible to suspend Amitraz powder in the eutectic melt mixture provided it remained in powder form. However, when liquefied (by melting), phase separation occurred. Thus the temperature of the eutectic mixture should be kept below the 80oC melting point of Amitraz. The dissolution tests were performed in a 10-liter Pyrex glass beaker with normal tap water (± 25oC). The time taken for complete dissolution was measured with a stopwatch. These results were confirmed with turbidity tests. Starch-based super disintegrants were used in an attempt to enhance the dissolution rate of the pellets. Explotab® improved the dissolution rate of 30% and 40% m/m Amitraz formulations slightly. The best formulation obtained in this study had the following composition (in m/m): 30% Amitraz; 8% CaCO3; 1 % Wettol D2; 2% Arkopal N090; 10% Explotab® and 49% urea – 1,3-dimethylurea eutectic. Such tablets disintegrated within 6,5 minutes when suspended in water.Dissertation (MSc (Applied Science))--University of Pretoria, 2007.
Chemical Engineering
MSc
unrestricted
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Zghebi, Salwa S., Matas Marcel de, Morgan C. T. Denyer, and Nicholas Blagden. "A Hydrocortisone Nanoparticle Dosage Form." 2011. http://hdl.handle.net/10454/4835.
Full textAbstract:
noOf particular importance in recent years has been the development of techniques for producing nanoparticles (NPs) of poorly-water soluble drugs with dimensions less than 1000 nm for which their high surface area can lead to improvements in bioavailability. Furthermore, the small size of these particles can also enable cellular uptake, particularly for positively charged systems. Therefore, an overall objective of this part of the project was to produce nanoparticles with different levels of positive surface charge using the bottom-up method.