Letteratura scientifica selezionata sul tema "Mini-matrix multiple unit dosage"

Solid oral dosage forms are most suitable dosage forms; preferably tablets are widely accepted by people of different age groups. Mini tablets are tablets with a diameter equal to or smaller than 2–3 mm. Mini tablets are multiple unit dosage forms and are advantageous than pellets or any other oral dosage forms as they are easy to manufacture and stability problems are less. Many types of mini tablets are there like bio adhesive mini tablets, pH responsive mini tablets, gastro retentive mini tablets, paediatric mini tablets, oral disintegrating mini tablets. Current ODT developments meet multiple pharmaceutical and patient needs, including better life-cycle management to easy treatment for paediatric, geriatric and psychiatric dysphagic patients. Orally disintegrating dosage forms are X suitable for patients, especially who find it inconvenient to swallow traditional tablets and capsules with an 8-oz glass of water for one reason or another. These essentially reduce the variation between subjects. Mini tablets which disintegrate orally can be evaluated by testing for dissolution, disintegrating testing and hardness. The need for non-invasive delivery systems continues due to the poor acceptance and enforcement by patients of current delivery schemes, limited market space for drug companies and product usage, coupled with high disease management costs. The review emphasizes on advantages of mini tablets, types, methods of manufacturing and modes of administration and evaluation of mini tablets.

Mini-tablets represent a new trend in solid dosage form design, with the main goal of overcoming some therapeutic obstacles. Mini tablets are multiple unit dosage forms and are advantageous than pellets or any other oral dosage forms as they are easy to manufacture and stability problems are less. Offering some therapeutic benefits such as dose flexibility and combined release patterns. They do not require any solvent for their production and also local irritation can be avoided by the use of mini tablet Mini tablet offer several advantages like they can be manufactured relatively easily, They are not require less coating materials and also there is a great flexibility during their formulation development. Mini tablet are more acceptable in children and elderly people as they are easy to swallow. The objective of controlled drug delivery systems is to reduce the frequency of the dosing and to increase the effectiveness of the drug by localization. Keywords: Mini-tablets, solid dosage form, oral dosage forms.

Abstract The goal of the present study is to prepare a stable, multiple-unit, extended-release dosage form containing oxycodone pellets coated with aqueous ethylcellulose (EC) dispersion, Surelease E-7-19050. The application of 18% w/w of EC leads to the similar drug release with the hydrophobic, non-swelling, matrix reference product containing 20 mg of oxycodone. Increasing the compression force to 9 kN and including more than 50% w/w of oxycodone pellets into the formulation resulted in faster drug release, indicating the damaging to the EC film coating. The physical appearance of the final formulation, assay of oxycodone, moisture content, and dissolution data over the stability period showed that the multiple-unit pellet system (MUPS) is efficient for the production of highly stable product.

Minitablets can be used either single or multiple unit sustained release dosage form. The objectives of this study were to prepare and evaluate the prolonged action, bioadhesive and slowly dissolving minitablets. The minitablets (Ø 2.5 mm, 7 mg) were prepared by direct compression method using 75%w/w of various hydrophilic polymers: hydroxypropylcellulose (HPC), hydroxypropyl methylcellulose (HPMC), carboxy methylcellulose (CMC), pectin (PT) and chitosan (CS). Spray dried lactose was used as diluent. Prior to compression, the angle of repose, bulk-tab density and %compressibility of each mixed powder were evaluated. The rate of hydration and erosion of the obtained minitablets were carried out in phosphate buffer (pH 7.4). The powder blends containing HPC, CMC or HPMC showed satisfactory flow properties and compressibility. Accordingly, the prepared matrix tablets of HPC, CMC and HPMC showed good physical properties such as hardness, while those of CS and PT showed poor properties. The degree of swelling were ranked as CS>CMC>PT>HPC>HPMC, while the erosion were ranked as CMC≈HPMC≈PT > HPC≈CS. Adhesion time of these minitablets on isolated pig intestine was >30 min for CMC, PT and CS tablets while HPC and HPMC tablets exhibited weaker bioadhesion. In conclusion, among tested polymers, CS, PT and CMC were appropriate for prolonged action, bioadhesive and slowly dissolving minitablets.

Multiparticulate drug delivery systems are mainly oral dosage form, consist of small discrete units that exhibit different characteristics especially in release pattern and drug bioavailability. These systems are represented by granules, pellets, microspheres, microcapsules, and minitablets. Pellets offer high flexibility in the design, formulation, and development of oral dosage forms such as sachet, suspension, capsule, and tablet. Multiparticulate tablets manufactured by compaction of multiple unite pellets is one of the latest and, yet, challenging technologies. Multiparticulate tablets combine the benefits of both a tablet and a pellet-filled capsule in one dosage form but their manufacturing experience many difficulties. The oral multiparticulate products consist of polymer-coated subunits or pellets, which are embedded in an inert excipients’ matrix, formulated to overcome the difficulty in administering capsules and improve the physicochemical stability of suspension and offer predictable release and uniform distribution in the gastro-intestinal tract compared to the plain tablet. This review discusses the advantages and drawbacks of MUPS, the properties of an ideal MUPS, various pharmaceutical applications of MUPS, the challenges and key variables that to be considered in the tableting process for successful production of MUPS Keywords: MUPS®, Pellets, Multiparticulate tablets.

Abstract Tumor environment in glioblastoma (GBM) is a dynamic interactive complex between tumor, immune and stem cells and extracellular matrix (ECM). In 226 patient glioma samples, we found a clinical correlation between expression of tumor vascular laminin-411 (α4β1γ1) and cancer stem cell (CSC) markers: Notch pathway members, CD133, Nestin, and c-Myc, with faster tumor recurrence and shorter survival of patients (Tao S, et al, Cancer Res., 2019). Novel nanotechnology approach to block trimeric ECM laminin-411 was developed for GBM treatment in experimental and preclinical models on human U87MG and LN229, and patient-derived TS543 and TS576 GBM cell lines. Nanobioconjugates (NBC) based on natural polymer, poly(β-L-malic acid), with antisense against laminin-411 α4 and β-chains, endosome escape unit (Ding H, et al, PNAS, USA, 2010), antibodies for blood-brain barrier (BBB) crossing and tumor targeting was characterized for toxicity and biodistribution according to FDA guidelines. Ex vivo depletion of laminin-411 α4 and β1 chains with CRISPR/Cas9 in human GBM cells led to reduced growth of intracranial tumors in mice, and significantly increased survival in hosts compared to mice with untreated cells. A nanobioconjugate potentially suitable for clinical use and capable of crossing BBB was designed to block laminin-411 expression. In biodistribution studies the NBC labeled with 125I on tyrosines of attached antibodies was accumulated in GBM but not in healthy brain tissue. Nanobioconjugate treatment of mice carrying intracranial GBM significantly increased animal survival and inhibited multiple CSC markers, Notch signaling system through the b1 integrin-Dll4 (Notch ligand) pathway. No toxicity revealed in 4 naïve Cynomolgus macaques after administration of three therapeutic 1X and acute 10X dosages of NBC. Conclusion: An efficient strategy of GBM treatment was developed via targeting a critical component of the tumor microenvironment, laminin-411, which is independent of heterogeneous genetic mutations in glioblastomas. Support: NIH grants U01CA151815, R01CA188743, R01CA206220, R01CA209921.

The purpose of any selected drug delivery system (DDS) is to deliver drug to target site and to get the desired drug concentration for effective therapy. The main purpose of designing controlled or sustained DDS is to decrease the frequency of dosing and maximizing its efficiency by confining the area of action of the drug to a selected region. It is well-identified that solid oral dosage form, particularly tablets, is the most satisfactory form of delivering medication. In addition, some new variations are emerging such as mini tabs which offer more formulation flexibility. Oral controlled release DDS are classified into two categories like single unit dosage forms which include tablets, capsules, and multiple-unit dosage forms include pellets, granules, or mini tablets. Mini tablets are a new development in solid dosage forms and more beneficial and great substitute for granules and pellets. Mini tablets defined as tablets which are having diameter <3 mm and promising patient friendly drug delivery system and more acceptable in small children’s and old age people as they are easy to swallow and offer therapeutic benefits such as manufactured relatively easy, dose and formulation flexibility, combination release pattern, coating, and less solvent requirement. Dose dumping and local irritation can be avoided using mini tablets. This review highlights the various advantages of mini tablets, manufacturing processes, formulation possibilities, and their challenges.

MUPS (Multiple Unit Pellets System): The oral route of drug administration is the most important and most user-friendly route of administration. In recent years, Multiple Unit Pellet Systems (MUPS) tablets are widely used in solid dosage form design. MUPS is considered to provide pharmacokinetic advantages compared to monolithic dosage forms. Typically, modified release pellets are contained in MUPS tablets. Modified release drug delivery systems have acquired very important role in pharmaceutical research and development.1 1.1Advantages of Compaction of MUPS over Conventional Modified-Release Tablets and/or Pellet-Filled Capsules and Tablets. The compression of multiparticulates into tablets, unlike the hard gelatin capsule, is a tamper-proof dosage form and has greater physicochemical and microbiological stability of pellets as they are embedment in the inert matrix. Tablets have less difficulty in esophageal transport than capsules. Tablets containing coated subunits can be prepared at a lower cost than these subunits filled into hard gelatin capsules because of higher production rate of the tablet press. The expensive control of capsule integrity after filling is also eliminated. In addition, tablets containing multiparticulates without losing the controlled-release properties could be scored, which allow a more flexible dosage regimen.

Mini-matrix multiple unit dosage forms (MUDFs) of diclofenac sodium and S(+) ibuprofen have been prepared. Normal tabletting techniques were used to form the mini-matrices prior to their enclosure in hard gelatin capsules. Four natural hydrophilic gums, namely xanthan, karaya, locust bean and carrageenan gums as well as hydroxypropyl methylcellulose (HPMC) were used as the principle release-retarding agents. Various excipients - lactose, Encompress®, cellulose acetate phthalate (CAP), Veegum F® and Avicel PH101® - were added in different proportions to further modify drug release. The diclofenac sodium mini-matrices (4.5 mm in diameter) were produced by the wet granulation method. The release profiles from several encapsulated minimatrices in phosphate buffer solution (pH 7.0) showed that xanthan, karaya and locust bean gums could sustain the release of diclofenac sodium while the carrageenan gum did not produce a satisfactory sustaining effect. The rank order of decreasing swelling rate in both axial and radial dimensions was xanthan > karaya > locust bean gum and each of these gums showed almost Fickian swelling behaviour. The solvent penetration rates were consistent with the swelling rates. However, the order of decreasing drug release and erosion rates was locust bean> xanthan > karaya gum. For each of these gums, the release behaviour was anomalous indicating that both Fickian drug diffusion and polymer relaxation were involved in the release process. The dominant mechanism depended on the nature and content of the gum, as well as the stage in the dissolution period. The study involving xanthan gum showed that the diclofenac sodium release rate declined linearly with a progressive increase in the gumcontent, without changing the release behaviour. However, for high drug: xanthan gum ratio (2:1), the release kinetics changed to Super Case II. Solubility differences between the excipients did not affect the release rate, but increasing proportions of each excipient produced a faster release rate with the release mechanism changing from anomalous to Case II and then to Super Case II transport. Mini-matrices containing HPMC produced faster drug release than those containing the three natural gums. There was no synergistic effect between xanthan and locust bean gums on the release of diclofenac sodium from mini-matrices. Variation in the stirring speed (used in the dissolution apparatus) and matrix volume had little effect on drug release, whereas the pH of the dissolution medium greatly affected the release of diclofenac sodium. Following on from the studies involving diclofenac sodium, xanthan and karaya gums were used to produce mini-matrices of S(+) ibuprofen. Excipients with good compressibility characteristics such as lactose, Encompress® and Avicel PH101® were needed in the formulations. At pH 7, higher drug release rates were obtained with karaya gum (Super Case II mechanism) compared with xanthan gum (anomalous behaviour). Solubility differences between the excipients slightly affected the release rate. Compression forces (11 - 26 kN) slightly affected the crushing strength. The minimatrices were relatively stable to variation in temperature (5 - 37°C) and relative humidity (10 - 75%) over a 2 month time period. These studies have shown that near zero-order release of diclofenac sodium and S(+) ibuprofen can be achieved using encapsulated mini-matrices formulations. The release mechanisms and release rates can be adjusted by variation of the type and content of gums and/or excipients.