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1
Dabros, Marta. "Pharmaceutical Polymorphs, Cocrystals and Solid Solutions." Digital WPI, 2009. https://digitalcommons.wpi.edu/etd-dissertations/30.
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Lawson, Sarah, Stacy D. Brown, Paul Lewis, and Gina Peacock. "Comparative Stability of Oral Vitamin K Solutions Stored in Refrigerated Amber Plastic Syringes." Digital Commons @ East Tennessee State University, 2018. https://dc.etsu.edu/etsu-works/5264.
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Purpose: Vitamin K1 (phytonadione) is a fat-soluble vitamin and an essential cofactor for the synthesis of clotting factors II, VII, IX, X, protein C, and protein S. Vitamin K antagonists deplete vitamin K reserves effectively preventing the synthesis of these clotting factors leading to anticoagulation. Overly excessive anticoagulation, as evidenced by INRs greater than 5, may necessitate vitamin K for reversal of warfarin depending on bleeding risk factors. For elevated INR without bleeding, the oral route is preferred. Orally administered vitamin K1 tablets are only supplied by a single manufacturer, and only available as a 5 mg tablet. Concerns with availability of this tablet, lack of dosing options for treatment requiring less than 5 mg, and delivery options for patients unable to swallow whole tablets have prompted the exploration of alternative dosing strategies using the 10 mg/mL injectable emulsion compounded into an oral liquid. The possibility of storing the oral liquid in unit-doses adds a layer of convenience, and is common practice in many hospital pharmacies. In this project, we compared oral liquid vitamin K1 in sterile water for injection (SWFI) to oral liquid vitamin K1 in Ora-Sweet, simple syrup, cherry syrup, and Syrpalta stored in amber plastic oral syringes.
Methods: Batches of 1 mg/mL vitamin K1 were prepared in SWFI, Ora-Sweet, simple syrup, cherry syrup, and Syrpalta and drawn up by 1-mL aliquots into amber plastic oral syringes. Syringes were capped and stored in a laboratory refrigerator (4.9-5.4oC). for the duration of the study. On each study day (0, 1, 2, 4, 7, 14, 21, 30, 60, and 90), three syringes from each vehicle were removed, and the contents diluted with ethanol to achieve a 0.5 mg/mL assay concentration. Additionally, USP reference material was used on each study day to prepare a fresh 0.5 mg/mL reference solution. The samples and reference were analyzed using a previously validated HPLC-UV method. Results were compared using a 2-way ANOVA (p = 0.05) with post-hoc Tukey’s correction for multiple comparisons. Product stability was defined as 90-110% labeled amount.
Results: Of the vehicles tested, SWFI was the most suitable vehicle for longer-term storage of unit-dosed vitamin K1. The 1 mg/mL vitamin K1 in SWFI, when stored in amber plastic oral syringes, remains within the acceptable 90 – 110% range for 21 days. The Syrpalta preparation demonstrated the next highest BUD of 7 days, with one syringe (2 injections) falling outside the 90% potency at the 14 day time point. Cherry syrup allowed for very limited stability, with a BUD of 24 hours. By the 48-hour time point, two of the three samples were below the 90% potency cutoff. For the vitamin K oral solutions prepared in simple syrup and Ora-Sweet, the recovery of vitamin K was not within acceptable limits, even on the day of compounding. The initial recovery for vitamin K in simple syrup was only 86.8%. Similarly, the preparation in Ora-Sweet, was not at acceptable potency on the day of compounding, (92.7 ± 9.9%). While the average recovery in Ora-Sweet exceeded 90%, the variability between samples suggests a lack of homogeneous distribution of drug through the vehicle. Statistically significant differences were detected between the SWFI preparation and all other vehicles in a 2-way ANOVA with Tukey’s multiple comparison post-test (p-value of 0.05). This difference was most pronounced between SWFI and Ora-Sweet and SWFI and simple syrup (both p < 0.0001). Cherry syrup was also vastly different from SWFI (p = 0.0002), and the difference between SWFI and Syrpalta was less pronounced, yet still significant (p = 0.0442).
Conclusion: Vitamin K1 in sterile water and Syrpalta was stable for 21 days and 7 days, respectively, when stored in amber plastic syringes. Vitamin K1 in cherry syrup was only stable for 24 hours in the syringes. For vitamin K1 in Ora-Sweet and simple syrup, the within-day variability was very high due to limitations in drug dissolution; as such the average recovery was not consistently above 90%, even on the day of compounding. Statistically significant differences were detected between the SWFI formulation and all other vehicles. Several factors appear to affect the potency and stability of vitamin K1 in different vehicles. Because the stability of vitamin K1 oral solution differs between storage in amber glass bottles and oral syringes, vitamin K1 may have the potential to adsorb to polypropylene (PPE). The pH of the vehicle may contribute to degradation of vitamin K1, and the viscosity of the vehicle may affect the achievable potency of certain mixtures. The viscosity of the mixture also appears to affect maintenance of a homogenous mixture, but the presence of alcohol in the vehicle may help aid in solubilizing the vitamin K1 in Syrpalta. Vitamin K1 in SWFI appears to be the most suitable vehicle for longer-term storage of unit-dosed vitamin K, but Syrpalta and cherry syrup may also be appropriate for more immediate use.
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Pinsuwan, Sirirat 1961. "Stability kinetics of 4-dedimethylamino sancycline, a new anti-tumor drug, in aqueous solutions." Diss., The University of Arizona, 1998. http://hdl.handle.net/10150/282753.
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4-Dedimethylamino sancycline (col-3) is a new antitumor antibiotic of the tetracycline family. Preformulation studies have indicated that col-3 is not stable in aqueous solutions. The overall purpose of this research project is to investigate the stability kinetics of this drug in aqueous solutions. The physicochemical properties of col-3, including melting point, UV spectrum, mass spectrum, dissociation constants and solubility were determined. Col-3 is an acidic compound with two pKₐ values of 5.9 (pKₐ₁) and 8.1 (pKₐ₂). It is slightly soluble in water (0.01 mg/mL) and readily soluble in organic solvents such as polyethylene glycol and benzyl alcohol. Although the solubility of col-3 increases with increasing pH, its stability decreases with increasing pH. A HPLC assay was developed to quantitate col-3 and separate its degradation products. Four major degradation products of col-3 were detected under alkaline conditions. These degradates were identified by their elution times and their UV-absorption spectra. The kinetics of degradation of col-3 in aqueous solution at 25°C were investigated by HPLC over the pH-range of 2-10. The Influence of pH, buffer concentration, light, temperature and some additives on the degradation rate were studied. The degradation of col-3 was found to follow first-order kinetics at 25°C. A rate expression covering the degradation of the various ionic forms of the drug was derived and shown to account for the shape of the experimental pH-rate profile. Under basic conditions, the degradation of col-3 involves oxidation, which is catalyzed by metal ions. The separation of the four initial degradation products of col-3 was investigated. Partial separation of these compounds is achieved by liquid-liquid extraction. However, due to the instability of these compounds, their complete isolation cannot be successful. The UV spectroscopic analysis of these compounds shows that an absorbance at 360 nm is partially decreased in degradates I and II and totally absent in degradates III and IV. These results suggest that the phenolic diketone moiety, which produces this absorption band, has been altered upon degradation.
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Boca, Madalina Brindusa. "Research into process validation in pharmaceutical companies, with specific reference to Roche, South Africa." Pretoria : [s.n.], 2009. http://upetd.up.ac.za/thesis/available/etd-10132009-181630/.
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Kerr, Helen Rosemary. "The surface properties of hyaluronic acid solutions in relation to joint lubrication." Thesis, University College London (University of London), 1985. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.308428.
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Lawson, Sarah, and Stacy Brown. "Stability of Oral Vitamin K Solutions Stored in Amber Plastic Syringes." Digital Commons @ East Tennessee State University, 2018. https://dc.etsu.edu/asrf/2018/schedule/102.
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Oral vitamin K is administered to patients who have very high INR lab values and are on warfarin therapy. Due to the inability of some patients to swallow tablets, and the commercial formulation of vitamin K being available only as a tablet or an injectable emulsion, it may be necessary to compound an oral liquid formulation. When compounding batches of oral solutions, it is sometimes convenient to measure the product in unit doses. In this project, we compared liquid vitamin K in sterile water (1mg/mL) verses liquid vitamin K in Ora-Sweet (1mg/mL) stored in amber plastic syringes. Vitamin K is light sensitive and is best stored in amber containers. Vitamin K is also lipophilic and may adsorb to the plastic syringes. In this study, we investigated the feasibility of bulk compounding oral vitamin K solutions, and aliquoting them for storage in amber plastic syringes. The Vitamin K in sterile water syringes were made by mixing 45 mL of sterile water and 5 ampules, each containing 10mg/mL of vitamin K emulsion, together in an amber glass bottle for a final concentration of 1mg/mL. Thirty 1mL plastic amber syringes were filled with the mixture, capped, and placed in the refrigerator. The same process was repeated using Ora-Sweet instead of sterile water to fill thirty more plastic amber syringes. Three syringes of vitamin K in sterile water mixture, three syringes of vitamin K in Ora-Sweet mixture, and one Vitamin K reference standard were all analyzed using HPLC-UV on the day of compounding, and at day 1, 2, 4, 7, 14, 21, 30, 60, and 90. If stability is defined as 90-110% active ingredient, then Vitamin K in sterile water is stable to fourteen days, 95.3±3.5% recovery, but some samples fell below 90% recovery after 14 days. By day ninety, the recovery in SWFI syringes was 84.2±8.9%. For vitamin K in Ora-Sweet, the within-day variability was very high due to limitations in drug dissolution; as such the average concentration was not consistently above 90%. On the day of compounding, the percent recovery in the Ora-Sweet syringes was 92.7±9.9%, despite 1 hour of stirring. In conclusion, the Vitamin K in sterile water mixture can be stored in refrigerated, amber oral plastic syringes for 14 days, but plastic amber syringes were not appropriate for storage of the Vitamin K in Ora-Sweet mixture.
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Thomas, P. H. "Studies on the pharmaceutical and clinical problems associated with the storage and administration of intravenous solutions." Thesis, Cardiff University, 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.372586.
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Brown, Stacy D., and Paul Lewis. "Stability Evaluation of Unit-Dose Vancomycin Hcl Oral Solutions in Plastic Capped Oral Syringes and Plastic Sealed Dosing Cups." Digital Commons @ East Tennessee State University, 2018. https://dc.etsu.edu/etsu-works/5263.
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Purpose:
Oral vancomycin is a first-line treatment for Clostridium difficile-associated diarrhea. Preparation of oral vancomycin solutions historically has been facilitated by extemporaneous compounding, using various formulas or compounding kits, such as FIRST® - Vancomycin. More recently, FIRVANQ™ (vancomycin HCl) for oral solution was approved by the FDA, replacing the FIRST® compounding kits. Preparation and storage of unit-doses of oral solutions can expedite delivery of the medication to the patient and reduce opportunity for dosing errors. In this study, we evaluated the stored stability of two preparations of vancomycin HCl oral solution (FIRST® – Vancomycin and FIRVANQ™), stored in oral syringes and dosing cups at refrigerated and room temperatures.
Methods:
Triplicate batches of vancomycin HCl oral solution (50 mg/mL) were prepared using FIRST® - Vancomycin and FIRVANQ™, aliquoted into plastic oral syringes and sealed dosing cups, and stored at refrigerated and room temperatures for a total of six batches. Additionally, remaining samples from FIRVANQ™ batches were unit-dosed in clear Luer-Lok™ syringes and stored under refrigeration as a seventh batch. Samples were removed and analyzed for vancomycin recovery using a previously validated high-performance liquid chromatography with ultraviolet detection (HPLC-UV) method over a 30-day period. Recovery was quantitatively assessed by comparing to a freshly prepared United States Pharmacopoeia (USP) reference standard on each day of sampling.
Results:
Stability was defined as recovery of 90 - 110% of labeled amount. For all tested samples, the chemical potency remained within the therapeutically acceptable window for the entire study period of 30 days. At room temperature, the FIRST® syringes and cups both retained 95% potency after 30 days. Under refrigeration, this product retained 100% potency and 91% potency in syringes and cups, respectively. Similarly, the FIRVANQ™ room temperature syringes were at 99% recovery and the room temperature cups at 95% recovery after 30 days. Refrigerated FIRVANQ™ retained a potency of 102% potency in the dosing cups after 30 days, and the both syringes types (clear and amber) were 97% and 101%, respectively, recovery during the study period.
Conclusion:
The percent recovery of vancomycin in each test group remains within 90 – 110% of the labeled amount throughout duration of study (0 – 30 days). Based on this study, unit-dosing has been shown to have a 30-day chemical stability. In this case, unit-dosing not only may be used to improve workflow and reduce dosing errors, but may also have an impact of reducing drug waste due to avoidance of discarding appropriately potent drug product. Additionally, stability within the study period was independent of storage container and condition. Finally, this unit-dosing practice for FIRVANQ™ is equally acceptable in the classic luer-slip amber plastic syringes, and the newer Luer-Lok™ clear plastic syringes.
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Méndez, del Río José Ricardo. "Solubility and phase transitions in batch and laminar-flow tubular crystallizers." Available online, Georgia Institute of Technology, 2004:, 2004. http://etd.gatech.edu/theses/available/etd-11182004-120908/unrestricted/mendezdelrio%5Fjose%5Fr%5F200412%5Fmast.pdf.
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Thesis (M.S.)--Chemical Engineering, Georgia Institute of Technology, 2005.Ronald W. Rousseau, Committee Chair ; William J. Koros, Committee Member ; Angus P. Wilkinson, Committee Member ; David J. am Ende, Committee Member. Includes bibliographical references.
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Barthe, Stephanie Cecile. "Investigation and modeling of the mechanisms involved in batch cooling crystallization and polymorphism through efficient use of the FBRM." Diss., Atlanta, Ga. : Georgia Institute of Technology, 2008. http://hdl.handle.net/1853/24752.
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Thesis (Ph.D.)--Chemical Engineering, Georgia Institute of Technology, 2009.Committee Chair: Dr Rousseau, Ronald W; Committee Co-Chair: Dr Grover Gallivan, Martha; Committee Member: Dr Realff, Matthew; Committee Member: Dr Garmestani, Hamid; Committee Member: Dr Nenes, Athanasios.
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Ridell, Annika. "Characterisation of Aqueous Solutions, Liquid Crystals and Solid State of Non-ionic Polymers in Association with Amphiphiles and Drugs." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis : Univ-bibl. [distributör], 2003. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-3607.
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Johnston, Andrew James. "The atomic structure of pharmaceuticals in solution." Thesis, University of Oxford, 2016. https://ora.ox.ac.uk/objects/uuid:817233d5-ea3a-4689-84a2-1de2c90f4f13.
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Investigations of the structure of indole, cocaine hydrochloride, alprazolam and clonidine hydrochloride in solution were undertaken using a combination of experimental, principally neutron di?raction, and computational techniques. This thesis aims to probe the interactions of the hydrophilic and hydrophobic groups of each these molecules with their solvent environment, drawing conclusions about how their interaction with solvent molecules and their conformation in solution are related to their biological function. Cocaine, alprazolam and clonidine are of particular interest because of their ability to cross the blood-brain barrier. Investigation of the solvation of indole, the functional group of the amino acid tryptophan, in methanol/water solutions highlighted the role played by electrostatic interactions between the benzene ring of indole and its environment in dictating the location of tryptophan in the membrane bilayer. By studying the hydration of cocaine in aqueous solution, a possible mechanism explaining the ability of cocaine to cross the blood-brain barrier in its protonated form, which involves shielding of its hydrophilic groups through a water mediated internal hydrogen bond, was proposed. The preferentially solvated regions of the benzodiazepine alprazolam in methanol/water solutions indicated that these regions coincide with the location of bridging water molecules in the crystal structure of alprazolam bound to the BRD4 protein, which regulates transcription of oncogenes. A similar analysis of the solvation of clonidine in methanol/water solutions supported hypotheses relating to the mechanism of action of clonidine occurring via binding to adrenoceptors rather than imidazoline receptors. The work presented in this thesis demonstrates the importance of determining the structure of biomolecules in solution in gaining a comprehensive understanding of their behaviour in vivo.
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Caron, Vincent. "MECANOSYNTHESE ET VITRIFICATION A L'ETAT SOLIDE D'ALLIAGES MOLECULAIRES." Phd thesis, Université des Sciences et Technologie de Lille - Lille I, 2006. http://tel.archives-ouvertes.fr/tel-00246474.
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Ce mémoire est consacré à la mécanosynthèse d'alliages moléculaires par cobroyage. Les composés étudiés sont des composés utilisés comme excipients dans l'industrie pharmaceutique. Il s'agit plus particulièrement du lactose, du tréhalose et du mannitol. Nos investigations ont montré la possibilité d'obtenir, sur une certaine gamme de concentrations, des solutions solides vitreuses homogènes tréhalose/mannitol et lactose/mannitol par cobroyage des poudres cristallines correspondantes. Elles ont aussi permis de montrer de manière originale l'influence de la position relative de la température de broyage par rapport à la température de transition vitreuse (Tg) sur la nature des états obtenus par broyage en faisant varier la zone de Tg des alliages par changement de composition chimique. Les transformations sous broyage des composés purs ont également été étudiées en détail. Le broyage du lactose et du tréhalose en dessous de Tg est à l'origine d'une transformation directe cristal -> verre à l'état solide. Par contre, le broyage des formes cristallines d et ß? du mannitol au dessus de Tg engendre une transformation polymorphique vers la forme cristalline a de stabilité intermédiaire montrant, de ce fait, le caractère stationnaire des états atteints au cours de ce type de transformations. De plus, nos investigations ont permis de déterminer un certain nombre de propriétés spécifiques de ces systèmes inaccessibles à partir des liquides purs et des mélanges liquides. La mutarotation du lactose a pu être caractérisée en détail. Les diagrammes de phases des mélanges lactose/mannitol et tréhalose/mannitol ont pu être établis. L'ensemble de ces résultats a été obtenu par DRX, RMN, DSC et ATG.
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Mendez, del Rio Jose R. "Solubility and phase transitions in batch and laminar-flow tubular crystallizers." Thesis, Georgia Institute of Technology, 2004. http://hdl.handle.net/1853/4876.
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The research addressed in this thesis focuses on monitoring and characterization of pharmaceutical compounds by laser backscattering. In particular, this study covers two topics: (1) the determination of naproxen sodium solubility in water, and its phase transition; and (2) comparisons of batch and laminar flow tubular crystallizers for the production of paracetamol (acetaminophen) and D-mannitol.
Using a Lasentec™ Focused Beam Reflectance Measurement (FBRM) device, the solubility of naproxen sodium in aqueous solutions was determined over a temperature range from 15.2 to 39.7 ℃ With the determination of the solubilities of two pseudopolymorphs, anhydrous and dihydrated naproxen sodium, the phase transition point between these two forms of the pharmaceutical compound was determined to occur at 30.3 ℃ Enthalpy of solution and metastable zone widths were also determined for the experimental conditions.
Crystallizations of paracetamol and D-mannitol were performed in a batch crystallizer and in a laminar flow tubular crystallizer (LFTC) system. In the latter system, supersaturation was generated rapidly in the solution being transported through a temperature-controlled tube and recovered in a batch vessel where product crystals were grown to equilibration. Because of the rapid rate at which supersaturation was generated in the LFTC, the resulting crystals were of smaller mean size than those obtained from batch crystallizations. The total time required for crystallization was significantly less with the LFTC than with the batch unit. Additionally, the rapid cooling in the LFTC led to the formation of two different polymorphs of paracetamol, Forms I and II.
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Corswant, Christian von. "Lecithin-based microemulsions for pharmaceutical use phase behavior and solution structure /." Lund : Lund University, 1998. http://catalog.hathitrust.org/api/volumes/oclc/68945035.html.
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Docherty, Andrea. "Crystal structure solution and refinement of pharmaceutical molecules using x-ray powder diffraction." Thesis, University of Strathclyde, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.399726.
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Levene, Clare. "Advanced Raman, SERS, and ROA studies of biomedical and pharmaceutical compounds in solution." Thesis, University of Manchester, 2012. https://www.research.manchester.ac.uk/portal/en/theses/advanced-raman-sers-and-roa-studies-of-biomedical-and-pharmaceutical-compounds-in-solution(1c05f618-b1c2-4663-870a-3d51b32dad7b).html.
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The primary purpose of this study was to investigate the combination of experimental and computational methods in the search for reproducible colloidal surface-enhanced Raman scattering of pharmaceutical compounds. In the search for optimal experimental conditions for colloidal surface-enhance Raman scattering, the amphipathic β-blocker propranolol was used as the target molecule. Fractional factorial designs of experiments were performed and a multiobjective evolutionary algorithm was used to find acceptable solutions, from the results, that were Pareto ranked. The multiobjective evolutionary algorithm suggested solutions outside of the fractional factorial design and the experiments were then performed in the laboratory. The results observed from the suggested solutions agreed with the solutions that were found on the Pareto front. One of the experimental conditions observed on the Pareto front was then used to determine the practical limit of detection of propranolol. The experimental conditions that were chosen for the limit of detection took into account reproducibility and enhancement, the two most important parameters for analytical detection using surface-enhanced Raman scattering. The principal conclusion to this study was that the combination of computational and experimental methods can reduce the need for experiments by > 96% and then selecting solutions from the Pareto front improved limit of detection by a factor of 24.5 when it was compared to the previously reported limit of detection for propranolol. Using the same experimental conditions that were used for the limit of detection, these experiments were extended to plasma spiked with propranolol in order to test detection of this pharmaceutical in biofluids. Concentrations of propranolol were prepared using plasma as the solvent and measured for detection using colloidal surface-enhanced Raman scattering. Detection was determined as <130 ng/mL, within physiological concentrations, previously achieved using separation techniques. The second part of this thesis also involved a combination of experimental and computational methods. Raman optical activity was utilized to investigate secondary structure of amino acids and diamino acid peptides in combination with density functional theory calculations. Amino acids are important biological molecules that have vital functions in the biological system. They have been recognized as neurotransmitters and implicated in neurodegenerative diseases. Raman and Raman optical activity experimental results were compared to determine site-specific acetylation, marker bands for constitutional isomers and identification of functional groups that interact with the solvent. The experimental spectra were then compared to those from the density functional theory calculations. The results indicated that; constitutional isomers cannot be distinguished from the Raman spectra but can be distinguished from the Raman optical activity spectra, site-specific acetylation can be identified from the Raman spectra, however, Raman optical activity provides more structural information in relation to acetylation. When the results were compared to the density functional theory calculations for the diamino acid peptides the results agreed reasonably well, however, agreement was not as good for the monoamino acids because diamino acid peptides support fewer conformations due to the peptide bond whereas monoamino acids can adopt a far greater number of conformations. Combined computational and experimental techniques have developed the ability to detect and characterize biomedical compounds, a significant move in the advancement of Raman spectroscopies.
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Gupta, Patel Salin. "MECHANISMS AND THERMODYNAMICS OF THE INFLUENCE OF SOLUTION-STATE INTERACTIONS BETWEEN HPMC AND SURFACTANTS ON MIXED ADSORPTION ONTO MODEL NANOPARTICLES." UKnowledge, 2019. https://uknowledge.uky.edu/pharmacy_etds/103.
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Nanoparticulate drug delivery systems (NDDS) such as nanocrystals, nanosuspensions, solid-lipid nanoparticles often formulated for the bioavailability enhancement of poorly soluble drug candidates are stabilized by a mixture of excipients including surfactants and polymers. Most literature studies have focused on the interaction of excipients with the NDDS surfaces while ignoring the interaction of excipients in solution and the extent to which the solution-state interactions influence the affinity and capacity of adsorption. Mechanisms by which excipients stabilize NDDS and how this information can be utilized by formulators a priori to make a rational selection of excipients is not known.
The goals of this dissertation work were (a) to determine the energetics of interactions between HPMC and model surfactants and the extent to which these solution-state interactions modulate the adsorption of these excipients onto solid surfaces, (b) to determine and characterize the structures of various aggregate species formed by the interaction between hydroxypropyl methylcellulose (HPMC) and model surfactants (nonionic and ionic) in solution-state, and (c) to extend these quantitative relationships to interpret probable mechanisms of mixed adsorption of excipients onto the model NDDS surface.
A unique approach utilizing fluorescence, solution calorimetry and adsorption isotherms was applied to tease apart the effect of solution state interactions of polymer and surfactant on the extent of simultaneous adsorption of the two excipients on a model surface. The onset of aggregation and changes in aggregate structures were quantified by a fluorescence probe approach with successive addition of surfactant. In the presence of HPMC, the structures of the aggregates formed were much smaller with an aggregation number (Nagg) of 34 as compared to micelles (Nagg ~ 68) formed in the absence of HPMC. The strength of polymer-surfactant interactions was determined to be a function of ionic strength and hydrophobicity of surfactant. The nature of these structures was characterized using their solubilization power for a hydrophobic probe molecule. This was determined to be approximately 35% higher in the polymer-surfactant aggregates as compared to micelles alone and was attributed to a significant increase in the number of aggregates formed and the increased hydrophobic microenvironment within these aggregates at a given concentration of surfactant.
The energetics of the adsorption of SDS, HPMC, and SDS-HPMC aggregate onto nanosuspensions of silica, which is the model solid surface were quantified. A strong adsorption enthalpy of 1.25 kJ/mol was determined for SDS adsorption onto silica in the presence of HPMC as compared to the negligible adsorption enthalpy of 0.1 kJ/mol for SDS alone on the silica surface. The solution depletion and HPMC/ELSD methods showed a marked increase in the adsorption of SDS onto silica in the presence of HPMC. However, at high SDS concentrations, a significant decrease in the adsorbed amount of HPMC onto silica was determined. This was further corroborated by the adsorption enthalpy that showed that the silica-HPMC-SDS aggregation process became less endothermic upon addition of SDS. This suggested that the decrease in adsorption of HPMC onto silica at high SDS concentrations was due to competitive adsorption of SDS-HPMC aggregates wherein SDS is displaced/desorbed from silica in the presence of HPMC. At low SDS concentrations, an increase in adsorption of SDS was due to cooperative adsorption wherein SDS is preferentially adsorbed onto silica in the presence of HPMC. This adsorption behavior confirmed the hypothesis that the solution-state interactions between pharmaceutical excipients such as polymers and surfactants would significantly impact the affinity and capacity of adsorption of these excipients on NDDS surfaces.
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BM, Khalid, and Priyanka Pulikanti Rani. "Impact of COVID-19 on pharmaceuticals industry to adapt digital marketing." Thesis, Högskolan i Gävle, Avdelningen för ekonomi, 2020. http://urn.kb.se/resolve?urn=urn:nbn:se:hig:diva-35234.
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This master thesis was prompted by the overall interest in Digital marketing that has been growing since the last decade. During this pandemic time, we are interested to know about the impact of COVID-19 on pharmaceutical industry. Most of the articles and the reports in the early stage were mainly about the concept of digital marketing, technology, implementation in day-to-day business. Lesser studies have been conducted keeping the pandemic in view. Covid-19 is the most influencing topic today around the world and because of this, digital marketing has become the important marketing strategy for every business to withstand in the market. We have chosen to work with the pharmaceutical company in an emerging country India to study the impact of Covid-19 on the pharmaceutical industry and how the industry is adapting digital marketing as their marketing strategy. The empirical study is designed as a qualitative method. We had conducted the interview with the employees of the marketing department, used digital marketing concepts from different literature, and applied to our study. We have also explained the selected methodology to answer our research questions. Our findings from the research have shown that digital marketing is the most effective marketing strategy for almost all businesses during this lockdown. The company we worked is believing that digital marketing has a long-run result. We had discussed about the marketing challenges faced by the pharmaceutical companies during pandemic, challenges of adopting digital transformation, strategies followed by the company to sustain customer loyalty by following the aspects of relationship marketing. Our research also focused to know about the solutions to overcome the challenges faced by the pharmaceutical companies.
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Akpinar, Isil. "Removal of pharmaceuticals and personal care products from aqueous solutions with metal-organic frameworks." Thesis, University College London (University of London), 2018. http://discovery.ucl.ac.uk/10046485/.
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This thesis focused on synthesising metal-organic frameworks (MOFs) and using them in liquid phase adsorption because of their tunable textural and chemical functional properties. Zirconium based MOFs, Zeolitic Imidazolate Frameworks (ZIFs) and MIL (Matérial Institut Lavoisier) family of MOFs have gained particular attention for many potential applications owing to their exceptionally high chemical, thermal and mechanical stability. The aim of this research was to determine MOFs`s viability as adsorbents for the remediation of water contaminated with pharmaceuticals, personal care products and also endocrine disrupting compounds, a known emerging class of organic contaminants. Removal of pharmaceutical compounds and endocrine disrupting compounds from water is of utmost importance due to the need for clean water and pollution prevention/mitigation. The selected MOFs, ZIF-8, UiO-66, UiO-67 and MIL-100(Fe) were synthesised. The materials were characterised using standard characterisation techniques including: Powder X-ray diffraction (PXRD), N2 sorption isotherm at 77 K and scanning electron microscopy (SEM). The materials were evaluated by batch adsorption experiments for the adsorptive removal of atrazine (pesticide), carbamazepine (antiepileptic), triclosan (antibacterial) and a binary mixture of carbamazepine and atrazine with having different hydrophobicity and hydrophilicity and kinetic diameter. Moreover, the regenerability of MOFs was investigated for the removal of range of organic contaminants of interest in this thesis. The observed results revealed that the MOF materials have potential use as promising adsorbents in treatment of contaminated water.
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Katayama, Derrick S. "Towards a mechanistic understanding of pharmaceutical protein stabilization in solution and the solid state /." Connect to full text via ProQuest. Limited to UCD Anschutz Medical Campus, 2006.
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Thesis (Ph.D. in Pharmaceutical Sciences) -- University of Colorado at Denver and Health Sciences Center, 2006.Typescript. Includes bibliographical references (leaves 159-173). Free to UCDHSC affiliates. Online version available via ProQuest Digital Dissertations;
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Heidari, Torkabadi Hossein. "Raman Microscopic Studies of Antimicrobial Reactions in Solution, Crystals, and Bacterial cells." Case Western Reserve University School of Graduate Studies / OhioLINK, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=case1448904373.
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Kalyva, Maria. "Fate of pharmaceuticals in the environment - A review-." Thesis, Umeå universitet, Institutionen för ekologi, miljö och geovetenskap, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-132995.
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The occurrence of pharmaceuticals in environment originating from human consumption has received increased scientific attention during the last decades due to concerns regarding their combined environmental effects in aquatic and terrestrial environments, in flora and biota and by extent in human health. In this review, I summarized the existing knowledge on the entire life cycle of pharmaceutical substances, from their exposure (sources) and fate to their effects on the natural environment. Since the negative effects of several drugs along with the environmental damage they entail are now known, it can be suggested that pharmaceutical companies make greener pharmaceutical products to reduce these effects to the terrestrial and aquatic environment. The present review could provide suggestions to improve the pharmaceutical environmental management globally, such as methodologies for monitoring systems, that need to be put in place for consistent data collection. Another area of research that is important is the release of pharmaceutical compounds in manufacturing plants as well as from landfill effluent. Finally, one more area with need for further research is green chemistry which could reduce or even eliminate the potential hazards of pharmaceutical compounds that enter the environment, irrespective to the source of entry.
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Sawangchan, Phawanan. "The effect of aggregation state on the degradation kinetics of Amphotericin B in aqueous solution." Diss., University of Iowa, 2017. https://ir.uiowa.edu/etd/5992.
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Amphotericin B (AmB) is an amphiphile antifungal agent composed of lipophilic and hydrophilic structures and is known to aggregate in aqueous solution. The effect of substrate aggregation on the degradation kinetics of aqueous AmB was studied.
Aggregation state of AmB (0.0108 mM) in 10.0%v/v methanol aqueous solutions were pH dependent. The dissociation equilibrium constant (Kd) values suggested that monomeric form was predominant in acidic and alkaline condition and aggregated form appeared predominantly in neutral condition. At methanol concentration above 35.0%v/v, 0.0108 mM AmB in reaction mixtures presented in a monomeric form regardless of pH.
The degradation pathways of AmB were found to be pH-dependent. The effect of oxidants, antioxidants, oxidation initiators and chelators suggested that AmB was susceptible to oxidation in acidic and neutral pH regions which led spectral changes associated with the heptaene moiety. In basic conditions (pH > 9), AmB underwent hydroxide-catalyzed ring-opening lactone hydrolysis.
A degradation model describing substrate loss was constructed based on the kinetics of substrate loss. The pH-rate profile displayed three regions: specific acid-catalyzed degradation at pH below 4, a specific basic-catalyzed hydrolysis at pH above 9 and a pH-independent degradation in the neutral pH range 4 – 9. The effect of methanol on degradation kinetics in the neutral pH region indicated that aggregated AmB was more susceptible to oxidative degradation than monomeric AmB.
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D'Silva, Joseph Baptist. "Stability of drugs in pharmaceuticals : kinetics and mechanisms of hydrolysis in liposomal suspensions and aqueous solutions /." Ann Arbor, Mich. : University Microfilms International, 1987. http://www.gbv.de/dms/bs/toc/01614533x.pdf.
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Archibald, Timothy, Paul Lewis, and Stacy Brown. "Stability of Vancomycin Hydrochloride for Oral Solution Stored in Unit Doses at Room and Refrigerated Temperatures." Digital Commons @ East Tennessee State University, 2018. https://dc.etsu.edu/etsu-works/5262.
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Khawam, Ammar. "Application of solid-state kinetics to desolvation reactions." Diss., University of Iowa, 2007. http://ir.uiowa.edu/etd/170.
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Kirk, Loren, and Stacy D. Brown. "Beyond-Use Date Determination for Buprenorphine Buccal Veterinary Solution Using Validated High-Performance Liquid Chromatographic Method." Digital Commons @ East Tennessee State University, 2013. https://dc.etsu.edu/etsu-works/5283.
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Garcia, Herbert Melendez, Manuel Maza Cortez, and Edgar Diaz Amaya. "Blockchain-based Website Solution for Controlling the Authorized Sale of Drugs in Peru." Institute of Electrical and Electronics Engineers Inc, 2020. http://hdl.handle.net/10757/656580.
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El texto completo de este trabajo no está disponible en el Repositorio Académico UPC por restricciones de la casa editorial donde ha sido publicado.Drug counterfeiting or adulteration is a worldwide concern due to the serious consequences they generate, especially in the health and economic sectors. This concern is greater in Peru, as it is among the top five countries with drug counterfeiting incidents in the Americas, according to a study carried out in 2018 by the Pan American Health Organization. In this paper, we present our project, which aims at implementing a technological solution that provides reliable information on the origin and authenticity of these products in Peru to the drug consumer user, preserving the security and integrity of the exposed information using Blockchain technology. Likewise, it allows showing detailed drug characteristics, such as: composition, pharmaceutical form, active ingredients, among other relevant information. The technological solution, proposed by our project, aims at publishing the commercial origin of drugs from their sale in laboratories and distributors to the sale to the public in pharmacies. In the development of this paper, a bibliographic review of research on the use of blockchain technology is presented, as well as its benefits in the health sector, the architecture used by the system and the conceptual commercialization chain that supports it, and the qualitative and quantitative validation for the drug query service is shown.
Revisión por pares
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Kirk, Loren Madden, and Stacy D. Brown. "Beyond-Use Date Determination of Buprenorphine Buccal Solution Using a Stability-Indicating High-Performance Liquid Chromatographic Assay." Digital Commons @ East Tennessee State University, 2015. https://dc.etsu.edu/etsu-works/5305.
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Objectives
The objectives of this study included developing and validating a stability-indicating high-performance liquid chromatographic (HPLC) method with ultraviolet (UV) detection for the determination of buprenorphine in a buccal solution for veterinary use, and applying that method to determine the stability of a 3 mg/ml buprenorphine preparation in room temperature and refrigerated storage conditions. This preparation, intended for buccal administration in feline patients, plays an important role in pain management in cats.
Methods
A stability-indicating HPLC method was developed and validated for system suitability, accuracy, repeatability, intermediate precision, specificity, linearity and robustness based on US Pharmacopeia (USP) General Chapter. The method was then applied to the study of potency changes over 90 days in a buccal buprenorphine solution stored at two temperatures.
Results
All HPLC-UV method data met acceptable criteria for the quantification of buprenorphine in a buccal solution formulation. The buprenorphine concentrations found in each stability sample remained within the 90–110% of label claim throughout the 90 days of study. All stability test bottles of the buprenorphine buccal solution retained their original appearance. For the room temperature bottles, some white particulate matter was noted in the threads of the container bottles starting at day 21. The pH of the preparations during the course of the study was in the range of 3.57–4.06 and 4.01–4.16 for the room temperature and refrigerated samples, respectively.
Conclusions and Relevance
Pharmacists have compounded a concentrated 3 mg/ml buccal solution to use easily in the home care or outpatient setting for treatment of feline pain. Prior to this investigation, pharmacists empirically assigned beyond-use dates to this formulation based on standards in USP General ChapterPharmaceutical Compounding – Nonsterile Preparations. This study of a 3 mg/ml buprenorphine buccal solution indicates stability through 90 days.
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Bauer, Horst Hermann. "Physical stability of peptide pharmaceuticals : aggregation and conformational changes of human calcitonin (hCT) in aqueous solution /." [S.l.] : [s.n.], 1995. http://e-collection.ethbib.ethz.ch/show?type=diss&nr=10989.
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Lucero, Borja Diego Sebastián. "Solubility and Dissolution Rate of Active Pharmaceutical Ingredients: Dissolution Media and Effect of Enhancers." Doctoral thesis, Universitat de Barcelona, 2021. http://hdl.handle.net/10803/671762.
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The present doctoral thesis is focused on the effect of pH, enhancers and biorelevant media in the Solubility and the Dissolution Rates of some selected acidic active pharmaceutical ingredients (API). Because of the effect of these physicochemical parameters in the bioavailability of drugs and their pharmacological action, deepen the knowledge on the factors affecting the dissolution properties is of paramount importance in the drug development process.
Solubility and dissolution rates are examined in different aqueous solutions and buffering systems, accounting for the pH values of main interest in the gastrointestinal tract (2.0, 5.8 and 6.5), together with dissolution media that simulate intestinal fluids in fasted (FaSSIF) and fed states (FeSSIF). It is also determined in these media and discussed the effect of some excipients intended as dissolution enhancers, such as cyclodextrins, polyvinylpyrrolidones and hydroxypropylcellulose. Finally, differential scanning calorimetry was used to identify solid-solid interactions between excipients and APIs. As a complementary investigation, this thesis also presents a comparative study of the reference shake-flask and potentiometric CheqSol methods for the determination of solubility, including APIs with different acid/base properties (acidic, amphoteric and basic).
The study confirms that solubility is pH dependent, and an accurate pKa determination of the drugs is needed to detect the presence of concurrent aggregation or complexation reactions affecting the amount of compound dissolved. As expected, the addition of excipients increases the solubility of APIs, but in different degrees depending on the drug, excipient, and pH conditions. Solubility in simulated intestinal fluids is generally improved, and the addition of excipients might increase, diminish or even cancel the enhancement, depending on the matrix formed. Interestingly, the factors improving the solubility of an API do not necessarily enhance its dissolution rate. The release of the drug from its compressed solid form (tablet) is a complex process, involving an aqueous boundary layer between the solid and the bulk solution.
The results of this thesis point out the need of systematic and detailed dissolution studies in the step of pharmaceutical formulation, as long as the enhancement produced by a particular excipient in a singular dissolution medium can be characteristic of an individual API, and these results cannot be uncritically extended to other drugs.La presente tesis doctoral se enfoca en el efecto del pH, excipientes y medios biorelevantes sobre la solubilidad y velocidad de disolución de algunos principios activos (PA). Dado el efecto de estos parámetros fisicoquímicos en la biodisponibilidad de los fármacos y su acción farmacológica, el profundizar en el conocimiento de los factores que afectan estas propiedades de disolución es de suma importancia en el desarrollo de medicamentos. La solubilidad y velocidad de disolución se examinan en diferentes soluciones y sistemas tamponadores, de acuerdo a valores de pH de interés del tracto gastrointestinal, junto a medios de disolución que simulan fluidos intestinales. También se determina el efecto que puedan tener en estos medios, sustancias como excipientes que aumenten la disolución, tales como ciclodextrinas, polivinilpirrolidonas e hidroxipropilcelulosa. Calorimetría diferencial de barrido fue utilizada para identificar interacciones sólido-sólido entre excipientes y PA. Complementariamente, en esta tesis también se presenta un estudio comparativo entre el método de referencia de equilibrio de fases y el método potenciométrico CheqSol para la determinación de solubilidad, incluyendo PA de diferentes propiedades fisicoquímicas. El estudio confirma la dependencia entre pH y solubilidad, una medición exacta del pKa de los fármacos es necesaria para detectar la presencia de agregados o complejos que afecten la cantidad de muestra disuelta. Como se esperaba, la adición de excipientes incrementa la solubilidad pero en diferente grado dependiendo del compuesto, el excipiente y las condiciones de pH. La solubilidad generalmente es mejorada cuando se usan medios biorelevantes, mientras que el uso de excipientes en estos medios podría incrementar, disminuir o cancelar el efecto de solubilización, dependiendo de la matriz formada. Sorpresivamente, los factores que incrementan la solubilidad no necesariamente lo hacen en la velocidad de disolución. La liberación del compuesto desde la superficie de la tableta es un proceso complejo, relacionado con la capa acuosa intermedia entre la tableta y la solución. Los resultados de esta tesis señalan la necesidad de estudios sistemáticos y detallados en el paso previo de formulación farmacéutica, pues la mejora producida por un excipiente en particular en condiciones singulares del medio, puede ser característica para un PA específico, y estos resultados no deben ser extrapolados sin criterio a otros fármacos.
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Kirk, Loren, and Stacy D. Brown. "Validated High-Performance Liquid Chromatographic Method for Buprenorphine Quantification in Oral Veterinary Solution for Application Toward a Beyond-Use Date Determination." Digital Commons @ East Tennessee State University, 2013. https://dc.etsu.edu/etsu-works/5286.
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Alfaro-Lopez, Lorenzo Josue. "Development of new conformationally and topographically constrained p60(c-src) PTK inhibitors. Solution and solid-phase approaches for the synthesis of delta-opioid receptor peptidomimetic ligands." Diss., The University of Arizona, 1999. http://hdl.handle.net/10150/288981.
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Based on the efficient substrate for p60ᶜ⁻ˢʳᶜ protein tyrosine kinase (PTK) YIYGSFK (1) (K(m) = 55 μM) obtained by combinatorial methods, we have designed and synthesized a series of conformationally and topographically constrained substrate-based peptide inhibitors for this enzyme. The inhibitors showed IC₅₀ values in low micromolar range (0.1-3 μM). A "rotamer scan" was performed by introducing four stereoisomers of β-Me(2')Nal in the postulated interaction site of peptide inhibitor (23) Y-c[D-Pen-(2')Nal-GSFC]KR-NH₂ (IC₅₀ = 1.6 μM). We found that the χ¹ space constraints imposed by the specialized amino acids, introduced at position 3 of peptide 23, were not as important as the configuration of the Cᵅ of that residue to recognize the active site of Src and Lck PTK, as reflected on the observed selectivity ratios. Cocrystallization studies between Lck and two of our inhibitors are in progress, in a collaboration with Dr. X. Zhu (Kinetix, Pharmaceuticals, Inc.). The results obtained may serve as the basis for the design of Lck and/or Src inhibitors, either peptide or nonpeptide. SL-3111 is a high affinity (IC₅₀ = 8.4 nM) and selective (μ/δ = 2020) δ-opioid receptor peptidomimetic ligand developed in Dr. Hruby's laboratory, as the result of extensive structure-activity relationship (SAR) studies based on peptide leads. However, bioassays (GPI and MVD) and in-vivo antinociception studies on the racemic mixture and both enantiomers of this compound, have shown particular problems such as low potency and toxicity. We have shown the importance of the piperazine ring in this molecule for binding toward the δ-opioid receptor. Thus, maintaining such scaffold we have studied a series of solution and solid-phase approaches toward the synthesis of SL-3111 analogues, which explore wider functional diversity at this heterocyclic ring. Compounds 64-67 were synthesized by solution methods. Analysis of the biological data and molecular modeling studies of these compounds, revealed an interesting trend in terms of the effects of the substituent at position two of the piperazine scaffold. Three different solid-phase protocols were explored toward the development of a combinatorial library of this type of compounds, which may facilitate future SAR studies.
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Kirk, Loren, and Stacy D. Brown. "High-Performance Liquid Chromatographic Method for a Compounded Vancomycin Oral Solution for Application Toward a Beyond-Use Date Determination." Digital Commons @ East Tennessee State University, 2014. https://dc.etsu.edu/etsu-works/5278.
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Zong, Zhixin. "Studies on the mechanisms of solid state and solution instability of drugs." Diss., University of Iowa, 2011. https://ir.uiowa.edu/etd/2795.
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The overarching objective of this thesis is to demonstrate a systematic approach for addressing the instability issues associated with low limit degradants by developing quantitative degradation models that incorporate key instability determinants into predictive equations. Chlorhexidine was used as model compound in aqueous solution to demonstrate the application of the predictive models to issues of formulation design and manufacturing. Chorhexidine degrades to p-chloroaniline, a well-established toxicant, by various pH-dependent pathways. In acidic conditions, the direct formation of p-chloroaniline from chlorhexidine is the major pathway whereas the indirect formation of p-chloroaniline via p-chlorophenylurea is the main alkaline pathway. Rate laws and mechanisms for each pathway were presented. Shelf life predictions equations for chlorhexidine formulations were derived based on the kinetics of p-chloroaniline appearance as a function of formulation strength, solution pH, bulk chlorhexidine purity and storage temperature. The pH range for optimal shelf-life was 5.0 to 5.5. Simple extraction procedures used during formulation preparation were identified to improve bulk chlorhexidine purity and thereby extend product shelf-life. Gabapentin degrades directly to gabapentin-lactam in the solid-state. The established limit on gabapentin-lactam in gabapentin pharmaceutical formulations is <0.5% w/w thus gabapentin instability was studied as a model compound for solid state formulation applications. Mechanical stress associated with drug product manufacturing in unit operations such as milling increased the subsequent lactamization rate upon storage due to increased gabapentin crystal disorder. The effect of environment moisture was to decrease the rate of gabapentin-lactam formation due to competitive recovery of gabapentin crystallinity which was accelerated by humidity. A degradation model that combined both physical and chemical instability pathways including autocatalytic branching, spontaneous intra-molecular cyclization and moisture-induced physical transformation steps was shown to be consistent with lactamization kinetics as a function of both environmental (temperature and humidity) and manufacturing-related effects. This kinetic model was used to predict the shelf-life of gabapentin tablets prepared under various exemplary manufacturing conditions thereby demonstrating the ability of the model to link manufacturing variation and shelf-life stability in for solid-state drug formulations.
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Rani, Rupam. "REMOVAL OF EMERGING CONTAMINANTS FROM AQUEOUS SOLUTION BY OZONE -BASED PROCESSES." Master's thesis, Temple University Libraries, 2013. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/214782.
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Civil EngineeringM.S.Env.E.
The presence of emerging contaminants (ECs) in water and wastewater systems has become a subject of significant concern worldwide. These emerging contaminants are complex organic molecules which potentially affect human health and environment. Conventional wastewater treatment plants are unable to completely remove these contaminants from water and therefore can discharge them into environment. The need to develop effective methods for ECs removal is essential. This study assess the potential of ozone based advanced oxidation processes (AOP) to oxidize number of emerging contaminants. Different combinations of ozone with hydrogen peroxide and sodium persulfate were tested. For this study 1-4, dioxane, perfluorinated compounds (PFCs), N,N-Diethyl-metatoluamide, and three pharmaceuticals sulfamethoxazole, trimethoprim and carbamazepine have been selected. The effect of different process parameters such as chemical dosages, ozone weight percent, ozone flow rates, etc. on destruction of ECs were examined. It was observed that 1, 4-dioxane were persistent to direct ozone reaction, however were easily oxidized by hydroxyl radical. However, ozonation was solely very effective (> 99 %) in removing pharmaceuticals such as sulfamethoxaole, trimethoprim and carbamazepine. It was not very efficient for the removal of perfluorinated compound and N,N-Diethylmeta-toluamide. The operational conditions were optimized for maximum removal of every compound and their influence on the degradation process is discussed.
Temple University--Theses
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Yu, Peng. "Studies of the adsorption of barbituric acid derivatives from solution by activated carbons - wet chemistry and computational chemistry." Diss., University of Iowa, 2019. https://ir.uiowa.edu/etd/6897.
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Adsorption processes are utilized in both medicine and industry. It is important to have an understanding of adsorption processes to better predict the outcomes and discern potential difficulties. The primary objective of this research is to further the understanding of the nature and extent of the adsorption process in solution, which is a function of the chemical composition of the adsorbates, adsorbents, and solvent.
This was accomplished by employing experimental studies as well as thermodynamic calculations and molecular dynamic simulations. Four activated carbons were used as the model adsorbents in this study. And, barbital, phenobarbital and primidone were used to elucidate the structural features of the adsorbates that were most responsible for the interaction with activated carbons. A Two-Mechanism Langmuir-Like Equation (TMLLE) was proposed to describe the independent presence of two adsorption mechanisms: non-site-specific adsorption and site-specific adsorption. The analyses of data generated by both previous investigators and current studies, suggest that the TMLLE allows an accurate analysis of the adsorption process. Based on the parameters in the TMLLE, the Modified Crisp Model and the van’t Hoff Model were employed to determine the Gibbs free energy changes for both site-specific adsorption and non-site-specific adsorption. Comparing the Gibbs free energy changes calculated by the Modified Crisp Model and the van’t Hoff Model (site-specific adsorption case), it is concluded that 5 water molecules are displaced by a phenobarbital molecule on the surface of activated carbons. And, for non-site-specific adsorption, it is concluded that 12 water molecules are displaced by a phenobarbital molecule on the nonpolar (hydrocarbon) part of the activated carbon surface. The adsorption of phenobarbital from solution by activated carbons has been simulated by employing Molecular Dynamic (MD) Modeling. The predicted differential Gibbs free energy values for site-specific adsorption at pH 2-9 were consistent with the thermodynamic calculations. And, the present MD simulations provide a good basis for the further understanding and quantitatively assessment of the adsorption driven by hydrophobic bonding. The conclusions reached in the current studies are expected to be applicable to a wide range of similar adsorption processes.
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Ji, Yuefei. "Photochemical and photocatalytic degradation of pharmaceutical and personal care products (PPCPS) in aqueous solution : a case study of atenolol and 2-phenylbenzimidazole-5-sulfonic acid." Phd thesis, Université Claude Bernard - Lyon I, 2014. http://tel.archives-ouvertes.fr/tel-01058226.
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In this thesis, the photochemical and photocatalytic degradation of atenolol (ATL) and 2-phenylbenzimidazole-5-sulfonic acid (PBSA) have been investigated in aqueous solutions. Our results show that direct photolysis of ATL is weak and the indirect photolysis, e.g., induced by photosensitizers such as nitrate, may contributed to its major loss process in natural sunlit waters. In the case of PBSA, direct photolysis is found to be important while the indirect photolysis may play a less important role in its elimination in natural surface waters. The photolytic reactions (either direct or indirect) generally obey pseudo-first-order kinetics and can be influence by the solution pH, the co-existence of other water constituents such as dissolved organic matter (DOM) and bicarbonate ion (HCO3-). The photolytic degradation lead to a variety of intermediates and products. However, the reduction in TOC of the photolysis is usually found to be insignificant compared to the disappearance of the mother compound. Nevertheless, the observed decrease in toxicity toward fresh water species D. magna in nitrate-induced photodegradation of ATL implies indirect photolysis of ATL is possibly an important way to reduce the toxicity to ecosystem. It should be noted that direct and indirect photodegradation may process through different pathways and mechanism as observed in the photolysis of PBSA in this work. Photocatalytic oxidation of ATL and PBSA were carried out in illuminated aqueous TiO2 suspensions. Photocatalytic reactions normally follow pseudo-first-order kinetics. The kinetics are strongly affected by the photocatalyst type, the photocatalyst dosage, the solution pH value and the substrate concentration. Hydroxyl radical (HO*) was determined to be the major reactive specie responsible for the remarkable degradation of mother compounds. The degradation efficiency is largely influenced by the water matrices as well as the formation and transformation of intermediates. It should be noted that Degussa P25 showed the highest photocatalytic activity for oxidizing ATL and PBSA compared to pure anatase or rutile catalyst such as Hombikat UV 100, Millennium PC 500 and Aldrich rutile, which is in line with previous reports. The photocatalytic degradation of mother compounds results in the formation of various intermediates (e.g., formic, oxalic, malonic acid) and inorganic ions (e.g., NH4+, NO3-, SO42-). TOC decreases much more slowly as compared to the disappearance of the mother compounds, however, complete mineralization could be obtained with longer irradiation time
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Yao, Liming. "Modeling, Analysis and Solution Approaches for Some Optimization Problems: High Multiplicity Asymmetric Traveling Salesman, Primary Pharmaceutical Manufacturing Scheduling, and Lot Streaming in an Assembly System." Diss., Virginia Tech, 2008. http://hdl.handle.net/10919/27961.
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This dissertation is devoted to the modeling, analysis and development of solution approaches for some optimization-related problems encountered in industrial and manufacturing settings. We begin by introducing a special type of traveling salesman problem called "High Multiplicity Asymmetric Traveling Salesman Problem" (HMATSP). We propose a new formulation for this problem, which embraces a flow-based subtour elimination structure, and establish its validity for this problem. The model is, then, incorporated as a substructure in our formulation for a lot-sizing problem involving parallel machines and sequence-dependent setup costs, also known as the "Chesapeake Problem". Computational results are presented to demonstrate the efficacy of our modeling approach for both the generic HMATSP and its application within the context of the Chesapeake Problem.
Next, we investigate an integrated lot-sizing and scheduling problem that is encountered in the primary manufacturing facility of pharmaceutical manufacturing. This problem entails determination of production lot sizes of multiple products and sequence in which to process the products on machines, which can process lots (batches) of a fixed size (due to limited capacity of containers) in the presence of sequence-dependent setup times/costs. We approach this problem via a two-stage optimization procedure. The lot-sizing decision is considered at stage 1 followed by the sequencing of production lots at stage 2. Our aim for the stage 1 problem is to allocate batches of products to time-periods in order to minimize the sum of the inventory and backordering costs subject to the available capacity in each period. The consideration of batches of final products, in addition to those for intermediate products, which comprise a final product, further complicates the lot-sizing problem. The objective for the stage 2 problem is to minimize sequence-dependent setup costs. We present a novel unifying model and a column generation-based optimization approach for this class of lot-sizing and sequencing problems. Computational experience is first provided by using randomly generated data sets to test the performances of several variants of our proposed approach. The efficacy of the best of these variants is further demonstrated by applying it to the real-life data collected with the collaboration of a pharmaceutical manufacturing company.
Then, we address a single-lot, lot streaming problem for a two-stage assembly system. This assembly system is different from the traditional flow shop configuration. It consists of m parallel subassembly machines at stage 1, each of which is devoted to the production of a component. A single assembly machine at stage 2, then, assembles products after components (one each from the subassembly machines at the first stage) have been completed. Lot-detached setups are encountered on the machines at the first and second stages. Given a fixed number of transfer batches (or sublots) from each of the subassembly machines at stage 1 to the assembly machine at stage 2, our problem is to find sublot sizes so as to minimize the makespan. We develop optimality conditions to determine sublot sizes for the general problem, and present polynomial-time algorithms to determine optimal sublot sizes for the assembly system with two and three subassembly machines at stage 1.
Finally, we extend the above single-lot, lot streaming problem for the two-stage assembly system to multiple lots, but still, for the objective of minimizing the makespan. Due to the presence of multiple lots, we need to address the issue of the sequencing of the lots along with lot-splitting, a fact which adds complexity to the problem. Some results derived for the single-lot version of this problem have successfully been generalized for this case. We develop a branch-and-bound-based methodology for this problem. It relies on effective lower bounds and dominance properties, which are also derived. Finally, we present results of computational experimentation to demonstrate the effectiveness of our branch-and-bound-based methodology. Because of the tightness of our upper and lower bounds, a vast majority of the problems can be solved to optimality at root node itself, while for others, the average gap between the upper and lower bounds computed at node zero is within 0.0001%. For a majority of these problems, our dominance properties, then, effectively truncate the branch-and-bound tree, and obtain optimal solution within 500 seconds.Ph. D.
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Douieb, Selim. "Étude de l’influence de l’écoulement sur la cristallisation en solution :Applications aux hydrates de dioxyde de carbone et à une substance pharmaceutique." Doctoral thesis, Universite Libre de Bruxelles, 2016. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/229010.
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La cristallisation en solution est une opération unitaire essentielle du génie chimique. Les conditions opératoires dans lesquelles cette opération est menée déterminent sa productivité et la qualité des cristaux produits, par le biais de l’influence qu’elles ont sur les cinétiques de germination et de croissance. De nombreuses études ont mis en évidence que les conditions d’écoulement influencent significativement ces deux cinétiques. Néanmoins, une compréhension profonde de la nature de cette influence n’a, à l’heure actuelle, pas encore été atteinte. Ceci cause bien souvent des problèmes tant au niveau du procédé que du produit et a également pour conséquence que l’effet des conditions d’écoulement sur les cinétiques de cristallisation est rarement exploité de manière à en tirer le meilleur avantage.La première partie de ce travail a été consacrée à l’étude de l’effet des conditions d’écoulement sur les cinétiques de cristallisation en solution (germination et croissance), avec pour cas pratique la cristallisation d’hydrates de dioxyde de carbone (CO2), une solution émergeante pour la capture et la séquestration du CO2 (gaz à effet de serre majeur).De manière à étudier l’impact des conditions d’écoulement sur le taux de formation des hydrates de CO2, des expériences de formation d’hydrates de CO2 ont été réalisées dans un réacteur de type cuve agitée de 20 L mis en œuvre de manière semi-continue dans des conditions d’écoulement variées, produites à l’aide de trois mobiles d’agitations différents (une turbine à pales inclinées, un MaxblendTM et un DispersimaxTM) opérés à différentes vitesses de rotations. Un modèle mathématique original de l'ensemble du processus de formation des hydrates de CO2 attribuant une résistance à chacune de ses étapes constitutives a été établi. Pour chaque condition expérimentale, le taux de formation est mesuré et l’étape limitante est déterminée sur base de la valeur des différentes résistances. Les trois mobiles d’agitations étudiés sont comparés relativement à leur efficacité et, pour chaque mobile, l’influence de la vitesse de rotation sur l’étape limitante est discutée. En l’occurrence, il est montré que des limitations dues aux transferts de chaleur peuvent se produire à l'échelle relativement petite utilisée dans cette étude.L’étude de l’impact des conditions d’écoulement sur la cinétique de germination des hydrates de CO2 s’est concentrée sur la caractérisation de l’effet du taux de cisaillement sur le temps d’induction associé à cette formation (proportionnel à cette cinétique). Cette étude a été basée sur la réalisation de mesure de temps d’induction au cours d’expériences de formation d’hydrates de gaz, utilisant le système CO2-H2O-tetrahydrofuran comme système modèle, réalisées dans un réacteur de type Couette-Taylor. L’application, à la phase liquide dans laquelle prend place la formation des hydrates de gaz, de différents taux de cisaillement (entre 50 et 300 s-1), maintenus constants tout au long de l’expérience de formation, a révélé que le temps d’induction moyen diminuait significativement lorsque le taux de cisaillement appliqué à la phase liquide augmentait. Il a été montré que cette diminution peut être principalement attribuée à une diminution du temps nécessaire à l’apparition de germes stables d’hydrates et à leurs croissances jusqu’à une taille macroscopiquement détectable. Il a également été montré que le temps d’induction moyen peut également être significativement réduit par l’application, à la phase liquide, d’un haut taux de cisaillement (900 s-1) durant une période relativement courte et définie.La seconde partie de ce travail a été dédiée au développement d’une stratégie permettant d’améliorer le contrôle des procédés de cristallisation de substances pouvant cristalliser sous plusieurs formes cristallines, et ce, relativement à la forme cristalline générée au cours et à l’issue de ces procédés. Le cas pratique de cette partie du travail est le développement d’un procédé de cristallisation en solution par refroidissement en mode batch d’un principe actif, récemment développé par la société pharmaceutique UCB, présentant deux formes cristallines connues. La robustesse et la reproductibilité de ce procédé vis-à-vis de la production de la forme cristalline d’intérêt et de la prévention de l’occurrence d’un phénomène de prise en masse, dû à une formation massive de cristaux de la forme cristalline indésirable, sont deux impératifs ayant guidés son développement.Le procédé qui a été envisagé dans le cadre de la deuxième partie de ce travail est basé sur la production de semences cristallines de forme I (la forme d’intérêt) par germination primaire au sein d’un réacteur tubulaire suivie d’une croissance de ces semences en milieu agité contrôlé en température. Les propriétés particulières de l’écoulement mis en œuvre au sein du réacteur tubulaire permettent d’y contrôler finement l’allure des champs de température et de concentration (et donc de sursaturation) et, de manière inédite, de circonscrire l’apparition de cristaux à la partie centrale de l’écoulement (afin de prévenir tout risque d’incrustation de la paroi interne du réacteur). Les expériences réalisées dans ce travail montrent que, associé aux conditions expérimentales utilisées, ce dispositif permet de produire des semences cristallines de forme I de manière reproductible. Elles montrent également qu’un contrôle adéquat des conditions initiales dans lesquelles les semences cristallines de forme I sont amenées à croitre ainsi que du taux de refroidissement utilisé pour entretenir cette croissance permet de garantir que celle-ci se déroule sans que le phénomène de prise en masse ne prenne place. Il est mis en évidence que ce contrôle repose sur la prévention de toute formation indésirable de cristaux de forme II par un maintient, en tout temps, d’un niveau de sursaturation ne dépassant pas une valeur critique donnée. Enfin, ces expériences montrent aussi que le type d’agitation utilisée dans ce travail n’a pas d’influence sur l’occurrence de la prise en masse mais a une influence majeure sur l’état de surface, la taille moyenne et la distribution en taille des cristaux produits.Solution crystallization is an essential unit operation in the chemical engineering field. Through their effect on the nucleation and growth kinetics, the operating conditions of such an operation determine its productivity and the quality of the produced crystals. An important number of studies have shown that the flow conditions have a significant influence on these two kinetics. Nonetheless, a deep understanding of the nature of this effect is still lacking, which often leads to severe difficulties in the development and operation of crystallization processes and impedes the emergence of positive applications of this effect.The first part of this work has been dedicated to the study of the effect of the flow conditions on the solution crystallization kinetics (nucleation and growth). Carbon dioxide (CO2) hydrate crystallization, an emerging method for the separation and capture of CO2, was used as a practical case.CO2 hydrate formation experiments have been performed in a 20 L semi-batch stirred tank reactor using three different impellers (a down-pumping pitched blade turbine, a Maxblend™, and a Dispersimax™) at various rotational speeds to examine the impact of the flow conditions on the CO2 hydrate formation rate. An original mathematical model of the CO2 hydrate formation process that assigns a resistance to each of its constitutive steps has been established. For each experimental condition, the formation rate is measured and the rate-limiting step is determined on the basis of the respective values of the resistances. The efficiencies of the three considered impellers are compared and, for each impeller, the influence of the rotational speed on the rate-limiting step is discussed. For instance, it is shown that a formation rate limitation due to heat transfer can occur at the relatively small scale used to perform our experiments.The investigation of the impact of the flow conditions on the nucleation kinetics of CO2 hydrates was focused on the characterization of the effect of the fluid shear rate on the induction time of gas hydrate formation (proportional to this kinetics). This study was based on induction time measurements during gas hydrate formation experiments, using the CO2-H2O-tetrahydrofuran system as model system, realized in a Couette-Taylor reactor. The investigation of the effect of the application of a constant shear rate (50 to 300 s-1) to the liquid phase from which the hydrates are formed revealed that the mean induction time decreases significantly as the applied shear rate increases. This could primarily be attributed to a decrease in the time required for stable gas hydrate nuclei to be generated and to grow to a macroscopically detectable size. The induction time could also be significantly reduced by the application of a high shear rate (900 s-1) to the liquid phase for a relatively short, defined period of time.The second part of this work has been dedicated to the development of a strategy for the improvement of the control of crystallization processes involving compounds able to crystallize under several crystalline forms, relatively to the crystalline form generated during and at the end of these processes. The strategy examined in this work was applied to the development of a batch cooling solution crystallization process of an active pharmaceutical ingredient, recently developed by the pharmaceutical company UCB, exhibiting two known crystalline forms. The robustness and the reproducibility of this process relatively to production of the desired crystalline form produced and the prevention of caking, due to the massive formation of crystals of the undesired crystalline form, were the two main priorities that have driven its development.The process considered in the second part of this work is based on the production of form I (the desired form) crystalline seeds through nucleation in a tubular reactor followed by the growth of these seeds in an agitated medium controlled in temperature. The particular properties of the flow conditions in the tubular reactor enable the temperature and the concentration fields, and therefore the supersaturation field, to be finely tuned and, in an original manner, to confine the emergence of new crystals in the center part of the flow (to prevent any fouling of the inner surface of the reactor). The experiments performed in this work showed that, coupled to the experimental conditions used, this device enables to reproducibly generate form I crystalline seeds. The experiments also revealed that a proper control of the initial conditions in which these seeds are brought to grow and of the cooling rate used to sustain this growth allows ensuring that this growth takes place without caking. It is shown that such a control lies on the inhibition of the formation of undesired form II crystals by keeping, at all times, the supersaturation level under a defined critical value. Finally, the experiments showed that the type of agitation used in this work does not influence the occurrence of caking but has a significant impact on the crystals surface quality, mean size, and size distribution.
Doctorat en Sciences de l'ingénieur et technologie
info:eu-repo/semantics/nonPublished
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Yu, Fang. "Mathematical Modeling of the Disposition of Binary Solutions of Topically Applied Agents in the Stratum Corneum and Underlying Skin Layers." University of Cincinnati / OhioLINK, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1627662280457926.
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Thakare, Kalpana. "THE EVALUATION OF LARCH ARABINOGALACTAN AS A NEW CARRIER IN THE FORMULATION OF SOLID DISPERSIONS OF POORLY WATER- SOLUBLE DRUGS." Diss., Temple University Libraries, 2013. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/232942.
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Pharmaceutical SciencesPh.D.
Advanced drug discovery techniques have produced more lipophilic compounds. Formation of an amorphous solid dispersion of such poorly water-soluble drugs improves their solubility and dissolution. This results in greater in vivo bioavailability. Thus, it is one of the recent trends in the development of oral dosage forms. In solid dispersions, the carrier is crucial for ensuring the functionality and stability of these systems. Larch arabinogalactan FiberAid grade (AGF) is generally recognized as safe (GRAS) designated, amorphous polymer. The objective of this dissertation project was to perform a comprehensive evaluation of AGF as a carrier for amorphous solid dispersions. First, a detailed characterization of the AGF polymer was performed. A special focus on its use as a solid dispersion carrier was emphasized. The glass transition temperature and the degradation temperature of the AGF polymer were ~82 oC and ~185 oC, respectively. The AGF polymer had good hygroscopicity. Ibuprofen-AGF solid dispersions were evaluated for dissolution enhancement. Ibuprofen-Hydroxypropyl methylcellulose grade K3 (HPMCK3) solid dispersions were investigated simultaneously as a control polymer dispersion. The ibuprofen-AGF solid dispersions were amorphous at nearly 20% ibuprofen load. The dissolution of the ibuprofen from AGF solid dispersions was significantly greater than that of the neat ibuprofen. The formation of the amorphous state of ibuprofen and solution-state ibuprofen-AGF interactions were the mechanisms of the ibuprofen dissolution enhancement. At a 10% ibuprofen load, the dissolution of the AGF solid dispersion was found greater than that of the dissolution of the HPMCK3 solid dispersion. Secondly, the itraconazole-AGF solid dispersions and the ketoprofen-AGF solid dispersions were characterized and compared them with the ibuprofen-AGF solid dispersions. The comparisons were established for the miscibility and dissolution enhancement. The order of increase in dissolution was ketoprofen-AGF solid dispersions > itraconazole-AGF solid dispersions> ibuprofen-AGF solid dispersions. The same order was observed for the solid-state miscibility of these drug-AGF solid dispersions. Additionally, the solid dispersions of 9 drugs with the AGF polymer were investigated to elucidate the detailed mechanism of drug crystallization inhibition by the AGF polymer. The inherent tendency of the AGF polymer to inhibit the drug crystallization, drug-AGF solid-state hydrogen bonding and the anti-plasticizing effect of AGF were the mechanisms underlying the crystallization inhibition by the AGF polymer. Last, a storage stability of ibuprofen-AGF amorphous solid dispersions after storage under accelerated conditions (for 3 months) and ambient conditions (for 6 months) was investigated. The amorphous ibuprofen from AGF solid dispersions was physically and chemically stable under stability conditions. In summary, the AGF polymer was evaluated as a novel carrier for formation of an amorphous solid dispersions. The studies established that the AGF polymer was comparable to HPMCK3 polymer. The AGF polymer could be more advantageous than the HPMC polymer for the preparation of solid dispersion when faster dissolution is desired at lower drug load.
Temple University--Theses
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Bai, Shujun. "Understanding physicochemical stability of proteins in solution and development of new analytical methods for freeze-dried protein formulations /." Connect to full text via ProQuest. Limited to UCD Anschutz Medical Campus, 2008.
Find full textAbstract:
Thesis (Ph.D. in Pharmaceutical Sciences) -- University of Colorado Denver, 2008.Typescript. Includes bibliographical references (leaves 134-146). Free to UCD Anschutz Medical Campus. Online version available via ProQuest Digital Dissertations;
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Elbagerma, Mohamed A. "Analytical method development for structural studies of pharmaceutical and related materials in solution and solid state : an investigation of the solid forms and mechanisms of formation of cocrystal systems using vibrational spectroscopic and X-ray diffraction techniques." Thesis, University of Bradford, 2010. http://hdl.handle.net/10454/4467.
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Analysis of the molecular speciation of organic compounds in solution is essential for the understanding of ionic complexation. The Raman spectroscopic technique was chosen for this purpose because it allows the identification of compounds in different states and it can give information about the molecular geometry from the analysis of the vibrational spectra. In this research the ionisation steps of relevant pharmaceutical material have been studied by means of potentiometry coupled with Raman spectroscopy; the protonation and deprotonation behaviour of the molecules were studied in different pH regions. The abundance of the different species in the Raman spectra of aqueous salicylic acid, paracetamol, citric acid and salicylaldoxime have been identified, characterised and confirmed by numerical treatment of the observed spectral data using a multiwavelength curve-fitting program. The non-destructive nature of the Raman spectroscopic technique and the success of the application of the multiwavelength curve-fitting program demonstrated in this work have offered a new dimension for the rapid identification and characterisation of pharmaceuticals in solution and have indicated the direction of further research. The work also covers the formation of novel cocrystal systems with pharmaceutically relevant materials. The existence of new cocrystals of salicylic acid-nicotinic acid, DLphenylalanine , 6-hydroxynicotinic acid, and 3,4-dihydroxybenzoic acid with oxalic acid have been identified from stoichiometric mixtures using combined techniques of Raman spectroscopy (dispersive and transmission TRS), X-ray powder diffraction and thermal analysis. Raman spectroscopy has been used to demonstrate a number of important aspects regarding the nature of the molecular interactions in the cocrystal. Cocrystals of salicylic acid - benzamide, citric acid-paracetamol and citric acid -benzamide have been identified with similar analytical approaches and structurally characterised in detail with single crystal X-ray diffraction. From these studies the high selectivity and direct micro sampling of Raman spectroscopy make it possible to identify spectral contributions from each chemical constituent by a peak wavenumber comparison of single-component spectra (API and guest individually) and the two- component sample material (API/guest), thus allowing a direct assessment of cocrystal formation to be made. Correlation of information from Raman spectra have been made to the X-ray diffraction and thermal analysis results. Transmission Raman Spectroscopy has been applied to the study cocrystals for the first time. Identification of new phases of analysis of the low wavenumber Raman bands is demonstrated to be a key advantage of the TRS technique.
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Paula, Daniel Jesus de. "DESENVOLVIMENTO DE FORMULAÇÃO NA FORMA DE SOLUÇÃO ORAL DE SILDENAFIL PARA USO NA DISFUNÇÃO ERÉTIL." Pontifícia Universidade Católica de Goiás, 2010. http://localhost:8080/tede/handle/tede/2125.
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Previous issue date: 2010-01-20The sprouting of sildenafil citrate (CSLD) was presented as an oral therapeutical form effective for Erectile Dysfunction Treatment, however, sidenafil, in the tablet form, has a period of latency of 30 to 40 minutes, being lengthened if administrated with foods. Liquid formulations present advantages regarding latency period when comparable to solid formulations, beyond being also a viable alternative for pediatric use in Pulmonary hypertension, for being easier to be administrated and for allowing dosage adjustment. The present work had developed pharmaceutical formulations like oral form of solution and had submitted them to tests in not controlled conditions and Accelerated Stability Test described in the Resolution RE no 1, July 29th of 2005. It was used as methodology of analysis for dosing of the active ingredient High pressure liquid chromatography (HPLC). The methodology was submitted to validation, obeying resolution RE no 899, May 29th of 2005.The solutions were tested initially in three concentrations (7,5, 5,0 and3.33%). The development of CSLD solutions was made in the 3,33%concentration, since in the other concentrations (5 and 7.5%), the active ingredient precipitated due to solubility problems in ambient temperature. The analytical methodology passed in the described tests of validation in the RE no 899 of May 29th of 2003 and showed a safe and efficient method to dosing CSLD in solution. The solutions with higher concentration of Soluphuor solutions kept throughout the time the characteristics of physical, chemical and microbiological stability, simulating the conditions of use in ambient temperature and through Accelerated Stability Test lead as Resolution RE no 1, July 29th of 2005 as well as in not controlled conditions (in use). While the solution with lower concentration of solvent demonstrated unstable regarding to the solubility due the lesser ratio of Soluphuor in the formulation, being therefore considered inadequate. Solutions when propagated in different liquids (water, beer, soda, whiskey)didn't have significant alterations regarding its organoleptics characteristics and nor had intervened with the physico-chemical stability concerning to the concentration of active ingredient. Concluding, the two solutions in the concentration of 3,33% formulated with bigger concentration of Soluphuor had presented good physical, chemical and microbiological stability and they possibly have easy industrial and commercial application therefore they can have lower time of latency in the Erectile Dysfunction.
O surgimento do citrato de sildenafil (CSLD) apresentou-se como uma terapêutica oral efetiva para o tratamento da Disfunção Erétil (DE), no entanto o sildenafil, na forma de comprimidos, tem um período de latência de 30 a 40 minutos, podendo se prolongar mais se for tomado com alimentos. As formulações líquidas apresentam vantagens quanto ao período de latência em relação às formulações sólidas, alem de ser uma alternativa viável para o uso pediátrico na Hipertensão Pulmonar, por ser mais fácil de ser administrado e por permitir o ajuste da posologia. O presente trabalho desenvolveu formulações farmacêuticas na forma de solução oral e as submeteram a testes em condições não controladas (de prateleiras) e Estabilidade Acelerada descritos na Resolução RE nº 1 de 29 de julho de 2005. Usou-se como metodologia de análise para doseamento do princípio ativo, a Cromatografia Líquida de Alta Eficiência (CLAE). A metodologia foi submetida à validação, obedecendo a resolução RE nº 899 de 29 de maio de 2003. Foram desenvolvidas inicialmente soluções em três concentrações (7,5, 5,0 e 3,33%) e com diferentes proporções de solvente Soluphuor®. As soluções de CSLD na concentração de 3,33% foram submetidas aos testes de estabilidade uma vez que as nas outras concentrações (5 e 7,5 %) houve precipitação do principio ativo por problemas na solubilidade a temperatura ambiente. A metodologia analítica foi aprovada nos testes de validação descritos na RE nº 899 de 29 de maio de 2003 e se mostrou um método seguro e eficaz para dosear CSLD em solução. As soluções com maior concentração de Solufuor mantiveram ao longo do tempo as características de estabilidade física, química e microbiológica, simulando as condições de uso em temperatura ambiente e através de estudo de estabilidade acelerado conduzido conforme Resolução RE nº 1 de 29 de julho de 2005 bem como em condições não controladas. Enquanto a solução com menor concentração do solvente se demonstrou instável quanto a solubilidade devido a menor proporção de Soluphuor ® na fórmula, sendo portanto, considerada inadequada. As soluções de CSLD na concentração 3,33% quando veiculadas em diferentes líquidos (água, cerveja, uísque e refrigerante) não tiveram alterações significantes quanto as suas características organolépticas e nem interferiram na estabilidade fisicoquímica quanto ao teor de principio ativo. Concluindo, as duas soluções na concentração de 3,33% formuladas com maior concentração de 2-pirrolidona apresentaram boa estabilidade física, química e microbiológica e possivelmente tenham fácil aplicação industrial e comercial pois podem ter o tempo de latência na Disfunção Erétil diminuído.
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Wolff, Justus Richard. "Bayer’s Pharmaceutical sales expansion through virtual solutions." Master's thesis, 2014. http://hdl.handle.net/10400.14/17559.
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The thesis describes Bayer’s expansion strategy through virtual solutions in the Brazilian
pharmaceutical market in 2013. The case study and analysis want to provide an international
strategy teaching material with the aim to offer students a ground to apply
and increase their knowledge based on real life examples.
Bayer is a global enterprise in the fields of healthcare, agriculture and high-tech polymer
materials with a history of more than 100 years in Brazil. The multinational recently
approached a disruptive innovation in form of an online salesforce system since the
healthcare segment suffered from high expenses for the sales force in the territorially
demanding Brazilian market.
Bayer could achieve prosperous results in a pioneering test of this virtual connection
between sales representatives and doctors and the decision about a final implementation
required further analysis. The management board was highly interested in conclusions
regarding the market attractiveness, the strategic positioning in relation to competition
and the strategic fit of the new approach. The overall analysis of these criteria resulted
in a recommendation for the implementation of the virtual sales force unit in Brazil.
The dissertation content is a case study reflecting the past events and a strategic analysis
of the virtual representatives concept as expansion strategy. The latter comprises an
assessment of macro- and microeconomic factors and the impact of the new concept on
the competitive landscape. Furthermore, it includes a SWOT and VRIO analysis of the
company and a review of the strategic fit and intent of the new virtual unit.
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Matteucci, Michal Elizabeth 1977. "Highly supersaturated aqueous solutions by design of amorphous pharmaceutical nanoparticles." 2007. http://hdl.handle.net/2152/16019.
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For 40% of currently discovered drugs which are poorly water soluble, engineering amorphous nanoparticles with rapid dissolution and enhanced solubility can improve their absorption. Antisolvent precipitation by mixing organic drug solutions with aqueous solutions produced sub-300 nm amorphous nanoparticle dispersions. Polymeric stabilizers increased the nucleation rate by lowering the interfacial tension and adsorbed to particle surfaces to inhibit growth by condensation and coagulation. An increase in the stabilizer concentration decreased the average particle size until reaching a threshold where the particles were < 300 nm for the poorly water soluble drug, itraconazole. The amorphous itraconazole nanoparticle dispersions dissolved at pH 1.2 to produce high supersaturation levels up to 90-times the equilibrium solubility. The supersaturation increased with particle curvature, as described qualitatively by the Kelvin equation. A thermodynamic analysis indicated the stabilizer maintained amorphous ITZ in the solid phase with a fugacity 90-times the crystalline value, while it did not influence the activity coefficient of ITZ in the aqueous phase. Recovery of the amorphous nanoparticles from water was achieved by adding salt to desolvate the polymeric stabilizers and flocculate the particles, which could then be rapidly filtered. The flocculation under constant particle volume fraction produced open flocs which were redispersible in water to their original ~300 nm size, after filtration and drying. Amorphous particles were preserved, as flocs were formed below the drug's glass transition temperature. After flocculation/filtration, medium surface area (2-5 m²/g) particles dissolved rapidly in pH 6.8 buffer with 0.17% surfactant to an unusually large supersaturation up to 17, comparable to that for high surface area (13-36 m²/g) particles. However, the decay in supersaturation was much slower for the medium surface area particles, as the smaller excess surface area of undissolved particles produced slower nucleation and growth from solution. In contrast, the maximum supersaturation was far lower for more conventional low surface area solid dispersions of drug in polymers, because of crystallization of undissolved solid during slow dissolution. The ability to design the particle morphology to manipulate the level in supersaturation in pH 6.8 media, offers new opportunities in raising bioavailability in gastrointestinal delivery.text
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KATDARE, ASHOK VISHWANATH. "REMINERALIZATION OF SYNTHETIC HYDROXYAPATITE POWDERS IN FLUORIDE SOLUTIONS." 1986. http://catalog.hathitrust.org/api/volumes/oclc/68297435.html.
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Lopes, Nuno Guerra. "Business plan: antimalarial solutions." Master's thesis, 2016. http://hdl.handle.net/10071/12427.
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JEL Classification: L65, M13Malaria is an infectious disease that have caused huge losses to the human being, mainly for those who live in malaria endemic regions. In one hand, public entities spend millions in methods to avoid the transmission, in the treatment of infected people or in the eradication of the disease. In the other hand, half of the human population is at risk and there is half million deaths yearly, being considered one of the most dangerous diseases. Additionally to those who live in endemic regions, millions of travellers visit endemic regions yearly, causing an increase of the problem. As follows, the awareness around this infectious disease has been increasing, mainly due to the increase of the tourism around the world. The incorrect use of the existing medicines has induced to increasing the parasite resistance, reducing the efficiency of those medicines. In this way, it is imperative the development and launching of new medicines that could solve this problem. This problem was detected and both pharmaceutical companies and other entities are increasing their efforts in research and development, in order to find new antimalarial medicines that may decrease the malaria burden. However, the investment needed to the development of new medicines is excessively high, which means that not all the companies and entities are capable of performing those activities. Considering what was said above, the main objective of this Business Plan is to analyse the economic and financial viability of the development of a new antimalarial medicine.
A malária é uma doença infeciosa que nos últimos anos tem causado enormes prejuízos para o ser humano, principalmente para aqueles que vivem nas regiões endémicas. Por um lado, todos os anos as entidades governamentais gastam milhões de euros em meios para evitar o contágio, no tratamento dos pacientes ou na erradicação da doença. Por outro, esta doença é das mais mortíferas no mundo, estando cerca de metade da população em risco de contágio, havendo centenas de milhar de mortes por ano. Para além das pessoas que vivem diretamente em contacto com a malária, milhões de viajantes visitam aquelas zonas anualmente, aumentando ainda mais o problema. Desta forma, a preocupação em torno desta doença tem vindo a aumentar, um pouco devido ao aumento dos fluxos de turismo mundial. Devido ao uso indevido dos medicamentos existentes, o parasita da malária tem vindo a ganhar resistência aos mesos, sendo estes medicamentos menos eficazes. Desta forma, torna-se urgente o desenvolvimento de novos medicamentos que possam fazer face a este cenário. Ao perceber este problema, tanto empresas farmacêuticas como outras entidades têm vindo a multiplicar esforços para que, através de investigação e desenvolvimento, apareçam novos medicamentos que atenuem as perdas provocadas pela malária. No entanto, o investimento necessário para desenvolver novos medicamentos é demasiado elevado e nem todas as entidades têm a capacidade para o fazer. Posto isto, o principal objetivo deste Plano de Negócios é o estudo da viabilidade económica e financeira do desenvolvimento de um novo medicamento que possa combater a malária.