Influence of Formulation Variable in Development of Floating Microspheres of Water Soluble Drug

Abstract

Floating drug delivery system for propranolol hydrochloride (PPL) was developed to prolong gastric residence time and increase drug bioavailability. The aim of present work was to prepare floating microspheres of propranolol HCl using solvent evaporation technique. Propranolol HCl is a non-selective beta adrenergic blocking agent with short elimination half life 3-5 hours. The short half life of propranolol HCl and multiple administration dose make propranolol HCl a very good candidate for formulation of floating drug delivery system. Total 27 batches were prepared by using 33 full factorial design, in which effect of drug polymer ratio, RPM and proportion of dispersion medium were studied. The prepared floating microspheres were evaluated for, particle size, percentage yield, in vitro buoyancy, drug content, entrapment efficiency, in vitro drug release, scanning electron microscopy and statistically analysed. Check point analysis was done to confirm the optimized batch. Stability of microspheres was studied as per ICH guidelines. It was observed that prepared microspheres were white, free flowing and spherical in shape. Formulation B25 prepared with drug:polymer ratio (1:5), RPM 1500 and proportion of dispersion medium(9:1) which exhibited higher percentage yield, in vitro buoyancy, entrapment efficiency and percentage drug release (96.09±0.17 %) after a period of 24 hrs. Results show that, an increase in drug polymer ratio, RPM and ratio of light liquid paraffin to n-Hexane affects the particle size, percentage yield, in vitro buoyancy and drug release of microspheres. It was observed that increase in drug polymer ratio increases the entrapment efficiency and mean particle size of the microspheres. Whereas, with the increase in RPM particle size of microsphere reduced and fine spherical shaped microspheres were produced. The data obtained in this study suggest that, floating microspheres of propranolol HCl with selected formulation variables are promising for sustained drug delivery which can reduce dosing frequency.