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 nonfickian 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.