DEVELOPMENT AND IN VITRO EVALUATION OF MUCOADHESIVE BILAYER BUCCAL TABLETS OF CARVEDILOL

Objectives: Carvedilol (CVD) is a nonselective β-adrenergic blocker that suffers from low absolute bioavailability (25-35%) due to first-pass metabolism. CVD-loaded buccal tablets were developed as a promising approach to overcome this limitation.Methods: The bilayers tablets were prepared by the direct compression technique. CVD-containing layer was based on one of four high molecular weight polymers; hydroxy propyl methylcellulose K15M (HPMC), Polyethylene oxide WSR N-750 (PEO), chitosan (CH) and Eudragit® RS-100 (EUD). An occlusive backing of ethylcellulose 20 (Ethocel®) was adopted as a second layer. The tablets were characterized for weight variation, thickness, friability % and drug content. Further studies were conducted to evaluate their swelling indices, surface pH, in vitro adhesion retention periods and in vitro drug release profiles.Results: The prepared tablets followed the compendial requirements for thickness, friability %, drug content and weight variation. The surface pH of all tablets ranged from 6.43 to 7.44 while their adhesion retention periods varied from 3.12 to 4.24 h. The best achieved system (PEO-based matrix; F4) displayed a reasonable adhesion retention period and a promising sustained drug release profile, over at least 8 hours, following non-fickian diffusion kinetics. This could indicate the contribution of swelling and erosion mechanisms for drug release.Conclusions: The current work succeeded in developing and evaluation of promising mucoadhesive CVD matrices suitable for buccal administration. Further pharmacokinetic and clinical studies are suggested to confirm the ability of the best achieved system to avoid the first pass metabolism of CVD and improve patient compliance.Â

دراسة صيدلية على أنظمة حفظ معدى نابضة لنقل بعض العقاقير المرتبه زمنيا

It is now well established that maintaining a relatively constant plasma drug level throughout the dosage interval is not considered as an optimum situation in many conditions. Relationships between drug presence, duration of action and safety may be influenced by, among other factors, circadian rhythms. Pulsatile delivery systems may release drug at the correct time as programmed from the system, but drug may be released into a region of the gastrointestinal tract where it is only poorly absorbed or, worse, not absorbed at all. These considerations led to the development of oral pulsatile release dosage forms possessing gastric retention capabilities that allow the systems to remain above or within the window of absorption, and extend the period of absorption of drugs exhibiting limited window of absorption in the upper gastrointestinal tract. A combination of gastroretentive and pulsatile principles offers an advantage that the system can achieve long residence time in the stomach, sufficient for delivering an adequate amount of drug at the right time, particularly in diseases requiring medication during sleeping and awakening. The press-coated tablet can be considered an example from Chrontropic system. It consists of a fast disintegration or modified release core, coated by compression with a solid barrier, commonly made of polymeric material, a diluent (as a release modifier) and drug (for both rapid and extended release). Press coated tablets may be modified to provide different release patterns, by varying the drug distribution and type of polymers used in the core and outer coating shell. It can be classified as a chronopharmaceutical technology, in that it provides a solid dosage form for drug delivery in a pulsatile fashion rather than continuously, and at predetermined times and sites following oral administration. Core in cup could be also considered as approach for gastroretentive pulsatile drug delivery. It consists of a core tablet containing the drug, an impermeable outer shell and top cover layer barrier of hydrophilic polymer. Water ingress into the osmotic core causes it to swell, rupturing the external coat and releasing the drug in pulsatile mode. In a trial to prepare a gastroretentive dosage form with pulsatile drug release profile, two approaches were investigated in this thesis. The oral bioavailabilities of the drugs from two selected formulae were compared to the commercial products in healthy human volunteers

Olmesartan medoxomil-loaded mixed micelles: Preparation, characterization and in-vitro evaluation

Olmesartan medoxomil (OLM) is highly lipophilic in nature (log p = 4.31) which attributes to its low aqueous solubility contributing to its low bioavailability 25.6%. OLM was loaded into mixed micelles carriers in a trial to enhance its solubility, thus improving its oral bioavailability. OLM-loaded mixed micelles were prepared, using a Pluronic® mixture of F127 and P123, adopting the thin-film hydration method. Three drug: Pluronic® mixture ratios (1:40, 1:50and 1: 60) and various F127: P123 ratios were prepared. OLM Loaded mixed micelles showed stability up to 12 h. The particle size of the systems varied from 364.00 nm (F3) to 13.73 nm (F18) with accepted Poly dispersity index (PDI) values. The in-vitro release studies of OLM from mixed micelles versus drug aqueous suspension were assessed using the reverse dialysis technique in a USP Dissolution tester apparatus (type II). The highest RE% (43%) was achieved with OLM-loaded mixed micelles (F8) when compared to (35%) of drug suspension

Development and In Vitro/In Vivo Evaluation of Etodolac Controlled Porosity Osmotic Pump Tablets

The aim of the current work was the design and evaluation of etodolac controlled porosity osmotic pump (CPOP) tablets exhibiting zero-order release kinetics. Variables influencing the design of (1) core tablets viz., (a) osmogent type (sodium chloride, potassium chloride, mannitol, and fructose) and (b) drug/osmogent ratio (1:0.25, 1:0.50, and 1:0.75), and (2) CPOP tablets viz., (a) coating solution composition, (b) weight gain percentage (1–5%, w/w), and (c) pore former concentration (5%, 10%, and 20%, v/v), were investigated. Statistical analysis and kinetic modeling of drug release data were estimated. Fructose-containing core tablets showed significantly (P < 0.05) more retarded drug release rates. An inverse correlation was observed between drug/fructose ratio and drug release rate. Coating of the optimum core tablets (F4) with a mixture of cellulose acetate solution (3%, w/v), diethyl phthalate, and polyethylene glycol 400 (85:10:5, v/v, respectively) till a 4% w/w weight gain enabled zero-order sustained drug delivery over 24 h. Scanning electron microscopy micrographs of coating membrane confirmed pore formation upon contact with dissolution medium. When compared to the commercial immediate-release Napilac® capsules, the optimum CPOP tablets (F4–34) provided enhanced bioavailability and extended duration of effective etodolac plasma concentration with minimum expected potential for side effects in healthy volunteers