BIOEQUIVALENCE MODULATION WITH MODIFIED STARCH IN ORODISPERSIBLE TABLETS IN COMPARISON TO MARKETED CONVENTIONAL TABLETS OF ROSUVASTATIN CALCIUM

*Tapas Kumar Pal, Debaditya Saha and S. Maity

ABSTRACT

Poor solubility and permeability of slightly soluble drug, Rosuvastatin calcium, often expose a problem of low bioavailability (absolute bioavailability 20%) as its dissolution and permeation are the rate limiting factors, so it becomes a challenge to improve dissolution and permeability of Rosuvastatin calcium oral conventional solid dosage forms. The dissolution profile and bioequivalence modulation of oral solid dosage form depend mostly on its formulation excipients and method of manufacture. Considering that in vitro dissolution studies can simulate in vivo bioequivalence of the therapeutically equivalent branded and generic versions of the same API, the present study had been targeted to explore bioequivalence modulation and justify interchangeability of marketed oral 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 commercially marketed formulations of Rosuvastatin Calcium 5 mg tablets along with the Orodispersible tablets of Rosuvastatin Calcium (5 mg) formulated with modified Starch by solid dispersion technique. In the present study modified Starch (Starch-5-phosphate) was prepared in the laboratory by reaction of starch with di-sodium hydrogen orthophosphate, anhydrous at elevated temperatures (>1300 C) and the product was found to be white, crystalline, non-hygroscopic powder, insoluble in water and aqueous fluids in acidic and alkaline pHs as well. It has no pasting or gelling property when heated at 1000 C in water for 30 min. As starch phosphate exhibited good swelling (> 400%) in water, it was evaluated as disintegrant in tablet formulations. Orodispersible Tablets of Rosuvastatin Calcium 5 mg were prepared by direct compression method using starch phosphate with PEG as solid dispersion in the ratio of Rosuvastatin calcium : PEG 6000 : Starch-5-phosphate in the ratio of 1:1:1 (F1cc), 1:2:5 (F4cc) and 1:1:9 (F5cc) and were evaluated. The dissolution efficiency (%DE5) obtained in Orodispersible tablet formulations were found as 84.22% (F1cc), 88.11% (F4CC) & 89.19% (F5cc) in comparison to 29.40% & 25.20% for CRESTOR & ROSUVAS (Branded commercial tablet formulations) justifying that Rosuvastatin solid dispersion with starch-5-phosphate as significantly better alternative than commercially marketed oral tablets of Rosuvastatin Calcium with faster dissolution and improved bioavailability. Furthermore, the results of the study revealed that ROZUCOR & ROSUVAS have been found bioequivalent and interchangeable with CRESTOR (Innovator Brand) having similarity factor (f2 value) > 50; whereas ROSUMAC & ZYROVA have not been found bioequivalent and interchangeable with CRESTOR (Innovator Brand) having similarity factor (f2 value) < 50. Incidentally, all the formulated Orodispersible tablets were found bioequivalent & interchangeable.

Keywords: Bioequivalence, Dissolution efficiency, Orodispersible, starch-5-phosphate, solid dispersion.