Controlled buccal patches of Zaleplon using melt granulation technique: An approach to overcome early morning awakening

Abstract

This study deals with the incorporation of melt granules in buccoadhesive patches prepared using polymers of opposing solubilities. Zaleplon (ZLP) is a Non-Benzodiazepine Hypnotic (NBZH) that suffers from extensive first pass hepatic metabolism and very short elimination half-life. The aim of this study was to develop a reliable dosage form that was capable of extending the release of ZLP to avoid early morning awakening so to improve sleep quality and also increase its bioavailability. ZLP was incorporated into Precirol-based melt granules and then further formulated into buccal patches prepared using HPMC, PVA and Ethyl cellulose. A Box-Behnken Design was adopted to statistically optimize the formulation variables, HPMC solution/PVA solution weight ratio, Precirol/ZLP ratio and percentage Ethyl cellulose. Fifteen formulae were prepared and evaluated regarding drug content uniformity, thickness uniformity, moisture loss, water sorption, mucoadhesion strength, surface pH, DSC and in-vitro release. The best achieved formula (composed of 5:1 Precirol:ZLP, 3:1 HPMC:PVA and 7.5% Ethyl cellulose) was able to control the release, where 87.24% of ZLP was released after 12 h and the patch showed acceptable mucoadhesion properties. The results revealed the ability of the developed ZLP buccal patches to be a candidate for overcoming early morning awakening.