Enhancement of Dissolution Rate and Formulation Development of Ritonavir Tablets Employing Starch Phosphate- a New Modified Starch

The objective of the study is to prepare, characterize and evaluate starch phosphate, a new modified starch as a carrier in solid dispersions for enhancing the dissolution rate of ritonavir. The feasibility of formulating solid dispersions of ritonavir in starch phosphate into compressed tablets with enhanced dissolution rate was also investigated. Starch phosphate was prepared by reacting starch with di-sodium hydrogen orthophosphate anhydrous at elevated temperatures. It was insoluble in water and has good swelling (400%) property without pasting or gelling when heated in water. Solid dispersions of ritonavir in starch phosphate were prepared by solvent evaporation method employing various weight ratios of drug: starch phosphate such as 2:1(SD-1), 1:1(SD-2), 1:2(SD-3), 1:3(SD-4) and 1:9(SD-5) and were evaluated for dissolution rate and efficiency. All the solid dispersions prepared gave rapid and higher dissolution of ritonavir when compared to pure drug. A 58.34 and 94.41 fold increase in the dissolution rate (K1) of ritonavir was observed with solid dispersions SD-4 and SD-5 respectively. The DE30 was also increased from 6.80% in the case of ritonavir pure drug to 76.25% and 84.05% in the case of these solid dispersions. Ritonavir (50 mg) tablets were prepared employing ritonavir alone and its solid dispersions SD-3 and SD-4 by wet granulation method and were evaluated. Ritonavir tablets formulated employing its solid dispersions in starch phosphate gave rapid and higher dissolution rate and DE30 when compared to plain and commercial tablets. A 9.95 and 28.14 fold increase in the dissolution rate (K1) was observed with tablet formulations containing solid dispersions SD-3 and SD-4 respectively when compared to plain tablets. INTRODUCTION: Ritonavir, a widely prescribed antiretroviral protease inhibitor drug belong to Class II under BCS and exhibit low and variable oral bioavailability due to its poor aqueous solubility. Its oral absorption is dissolution rate limited and it requires enhancement in solubility and dissolution rate for increasing its oral bioavailability. Several techniques 1 such as micronization, cyclodextrin complexation, use of surfactants and solubilizers, solid dispersion in water soluble and dispersible carriers, use of salts, prodrugs and polymorphs which exhibit high solubility , microemulsions and self emulsifying micro and nano disperse systems have been used to enhance the solubility, dissolution rate and bioavailability of poorly soluble drugs. Among the various approaches, solid dispersions in water dispersible excipients are simple, industrially useful approach for enhancing the solubility, dissolution rate and bioavailability of poorly soluble drugs.