Abstract

BIOEQUIVALENT MODULATION BY ADDING STARCH-5- PHOSPHATE AND SOLID DISPERSION OF ROSUVASTATIN CALCIUM IN SUBLINGUAL TABLET

*Debaditya Saha, Tapas Kumar Pal and Subhasis Maity

ABSTRACT

During the last two decades, pharmaceutical formulators have tried different processing methods as well as different modified excipients to improve therapeutic efficiency of drug delivery systems. The dissolution profile and bioequivalence modulation of oral solid dosage form depend mostly on its formulation excipients and method of manufacture. Improving bioavailability of oral solid dosage forms by increase in dissolution of poorly soluble drugs using solid dispersion technique presents a challenge to the formulation scientists. Considering that in vitro bioequivalence studies can simulate in vivo bioequivalence of the therapeutically equivalent branded and generic versions of the same API, the present study had been performed to explore bioequivalence modulation and justify interchangeability of marketed drug products by comparing the multipoint in vitro dissolution profile, per cent cumulative drug release (%CDR), dissolution efficiency (DE) and the similarity factor (f2) among different marketed formulations of Rosuvastatin Calcium 5 mg tablets along with the sublingual tablets of Rosuvastatin Calcium (5 mg) formulated by solid dispersion technique. Starch-5-phosphate was prepared in the laboratory by reaction of starch IP with di-sodium hydrogen orthophosphate anhydrous (AR) at elevated temperatures (>130OC) and the product was found to be white, crystalline, non-hygroscopic powder, insoluble in water and aqueous fluids in acidic and alkaline pHs. Rosuvastatin calcium, a widely prescribed anti-hyperlipidemic, HMG-CoA reductase inhibitor, belonging to BCS class II, reduces low density lipoprotein (LDL) cholesterol and triglycerides (TG) and increases high density lipoprotein (HDL) in patients with hypercholesterolemia and dyslipidemia. The dissolution efficiency (DE5) obtained in our modified sublingual tablet formulations F4 & F5 are found as 101.1% & 100.5% in comparison to 29.4% & 25.2% for CRESTOR & ROSUVAS (Branded commercial tablet formulations) confirming Rosuvastatin solid dispersion with starch-5-phosphate as significantly better than commercially marketed oral tablets of Rosuvastatin Calcium with faster dissolution and improved bioavailability.

Keywords: Rosuvastatin calcium, hyperlipidaemia, immediate release, sublingual, starch-5-phosphate, solid dispersion, cross carmellose, bioavailability.