Bifunctional capsular dosage form: Novel fanicular cylindrical gastroretentive system of clarithromycin and immediate release granules of ranitidine HCl for simultaneous delivery

Abstract

The study was aimed to develop a bifunctional single unit capsular system containing gastroretentive funicular cylindrical system (FCS) for controlled local delivery of clarithromycin and immediate release of ranitidine HCl. A 2(3) full factorial design was used to prepare gastroretentive FCS of clarithromycin using polyacrylamide (PAM), HPMC E15LV and Carbopol 934 P. The FCSs were evaluated for % cumulative drug release, floating time and in vitro detachment stress. Among the eight formulations, FCS5 (containing PAM and Carbopol 934 P at high and HPMC E15LV at low levels) showed % cumulative drug release of 97.09±1.14% in 8 h, floating time of 3 h and detachment stress of 8303.64±0.34 dynes/cm(2). Evaluation of optimized FCS by novel dynamic in vitro test proved superior bioadhesivity than cylindrical system under aggressive simulated peristaltic activity. Magnetic resonance imaging elucidated zero order release via constant swelling and erosion of FCS5. In vitro permeability across gastric mucin ensured its potential for effective eradication of deep seated Helicobactor pylori in gastric linings. The optimized FCS was combined with immediate release granules of rantidine HCl to get a bifunctional capsular dosage form. In vitro simultaneous drug release of clarithromycin and rantidine estimated by Vierordt's method exhibited a controlled drug release of 97.72±0.4% in 8 h for clarithromycin through FCS5 and 98.8±1.2% in 60 min from IR granules of ranitidine HCl. The novel system thus established its capability of simultaneous variable delivery of acid suppression agent and macrolide antibiotic that can be advantageous in clinical setting.