Optimization of diltiazem hydrochloride loaded mucoadhesive floating microspheres using calcium carbonate as gas generating agent as floatation aid

Abstract:

Considering the advantages offered by oral prolonged release multiparticulate gastroretentive dosage forms for drugs with narrow absorption window, the objective of this study was to develop mucoadhesive floating microspheres of diltiazem hydrochloride that is anticipated to overcome poor oral drug bioavailability. A 32 full factorial design was employed for optimization wherein concentration of ethyl cellulose and carbopol 934P were chosen as independent variables. Calcium carbonate used as gas generating agent to aid floatation. Percentage buoyancy, mucoadhesion and percentage cumulative drug release for 8 h were taken as dependent variables. A total of nine formulations (F1-F9) were developed by emulsion-solvent evaporation method and evaluated. The particle size, percentage entrapment efficiency, percentage buoyancy, percentage mucoadhesion and percentage cumulative drug release of the optimized formulation (F7) was found to be 160.2±18.87µm, 55.49±1.44%, 84.83±3.89%, 90.66±3.46% and 90.38±1.34% respectively. The in vitro drug release best fitted Higuchi kinetics and the experimental design was validated by extra design check point. DRS revealed no chemical interaction between the drug and polymer used. The spherical shape of microspheres was defined using SEM. DSC and XRD confirmed molecular dispersion of the drug in the microspheres polymeric matrix. The optimized formulation was found to be stable for a period of 3 months.

Key words: Diltiazem hydrochloride, mucoadhesive floating microspheres, optimization, stability.