Gastroretentive Floating Microspheres of Silymarin: Preparation and In Vitro Evaluation

Purpose: To prepare and evaluate floating microspheres of silymarin for prolonged gastric residence time and increased drug bioavailability.
Methods: Cellulose microspheres - formulated with hydroxylpropyl methylcellulose (HPMC) and ethyl cellulose (EC) - and Eudragit microspheres - formulated with Eudragit® S 100 (ES) and Eudragit® RL (ERL) - were prepared by an emulsion-solvent evaporation method. The floating microspheres were evaluated for flow properties based on parameters such as angle of repose and compressibility index, as well as for various other physicochemical properties including particle size, incorporation efficiency, in vitro floatability, and in vitro drug release. The shape and surface morphology of the microspheres were characterised by optical and scanning electron microscopy.
Results: Mean particle size increased while drug release rate decreased with increasing EC and ES contents of cellulose and Eudragit microspheres, respectively. Scanning electron microscopy showed pores on the surface and interior of the microspheres. The microspheres exhibited prolonged drug release for 12 h while still remained buoyant. Drug release kinetics, evaluated using the linear regression method, followed Higuchi kinetics and drug release mechanism was of the non-Fickian type.
Conclusion: The developed floating microspheres of silymarin exhibited prolonged drug release in simulated gastric fluid for at least 12 h, and, therefore, could potentially improve the bioavailability of the drug as well as patient compliance.

Keywords
Gastroretentive; Prolonged release; Silymarin; Floating microspheres; Ethyl cellulose; Hydroxypropyl methyl cellulose; Eudragit