Abstract

Gastroretentive drug delivery systems might enhance bioavailability of some drugs formulated in sustained release dosage forms by providing a longer residence time in the stomach. The aim of this study was to develop and evaluate a swellable floatable gastroretentive drug delivery system applying an effervescent mechanism using two gassing agents: calcium carbonate and sodium carbonate. Cefalexin monohydrate was used as a model drug since it has a short half-life of approximately 1 h and is instable at intestinal pH; its narrow absorption window at the upper gastrointestinal tract (GIT) made it ideal model drug for the gastroretentive delivery systems. Methods: a binary (1:1) mixture of hydroxyethyl cellulose and sodium alginate containing the drug at 250mg dose, with either 10% or 20% w/w calcium carbonate or sodium carbonate, was used to prepare floating tablets from either powder admixtures or granulated powders. The possible interactions between the drug and excipients were analysed using differential scanning calorimetry and Fourier transform infrared spectroscopy. The drug release characteristics, floating capacity and swelling behaviours of drug-loaded matrix tablets were evaluated in 0.1 M HCl (pH 1.2) at 37°C ± 0.5°C. Release data were analysed by fitting the power law model of Korsmeyer–Peppas, which describes the drug release from polymeric systems. The stability of all tablets (stored at 40±2°C and 80±5% RH for 3 months) prepared from a granular origin was evaluated for drug release rate, and floating capacity. Results: tablets floated on the surface of the dissolution medium, and drug release was sustained over 10 hours. Tablets produced from granules with 10%(w/w) calcium carbonate were promising with respect to their floating lag time, floating duration, swelling ability, sustained drug release rate, and stability results. Accordingly, calcium carbonate revealed promising results not only with cefalexin monohydrate at high dose but also with pentoxifylline at low dose in our previous research; hence to conclude this study shows that a binary mixture of hydroxyethyl cellulose and sodium alginate, together with calcium carbonate as a better choice of gassing agents is feasible to be applied with other drugs intend for gastroretentive delivery systems.