Formulation and Evaluation of a Gastric Retentive Drug Delivery System to Improve the Oral Bioavailability and Therapeutic Efficacy of Clopidogrel

Abstract

Clopidogrel, a widely prescribed antiplatelet agent, exhibits poor oral bioavailability due to limited solubility at alkaline pH and a narrow absorption window. Gastric retentive drug delivery systems (GRDDS), particularly floating drug delivery systems (FDDS), have emerged as promising strategies by prolonging gastric residence time and enhancing drug absorption. This study aimed to formulate and evaluate a gastroretentive floating tablet of Clopidogrel Bisulphate to improve its bioavailability through sustained drug release and extended gastric retention. Tablets were developed using compression techniques with polymers (hydroxypropyl methylcellulose) and effervescent agents. The formulations underwent pre- and post-compression evaluations, including hardness, friability, weight variation, floating lag time (FLT), total floating time (TFT), drug content uniformity, and in vitro dissolution behavior. Compatibility studies used UV-visible spectroscopy, FTIR spectroscopy, and differential scanning calorimetry. Among six formulations, F6 showed superior performance with favorable physicochemical properties, minimal floating lag time (7.29 ± 0.055 seconds), extended floating duration (>24 hours), and sustained drug release (98.97% over 24 hours). The drug release kinetics followed the Korsmeyer-Peppas model (R² = 0.977; n = 0.499), indicating non-Fickian diffusion. The optimized formulation demonstrated rapid buoyancy and sustained floating over 12 hours, with controlled drug release. Stability studies under ICH guidelines for three months showed consistent physical integrity, floating characteristics, and drug content. The developed gastroretentive floating tablet successfully prolonged gastric residence and achieved sustained drug release, suggesting potential enhancement of oral bioavailability and therapeutic performance. This approach may apply to drugs with similar absorption profiles.