Formulation and optimization of liquisolid tablet for improving the dissolution profile of rivaroxaban by using DoE approachand antithrombic activity

Abstract

Liquisolid technique is used in delivery of lipophilic and poorly water soluble drugs through oral route. It involves dissolving water insoluble drugs in nonvolatile solvents and converting into acceptably flowing and compressible powders. The present work was aimed to enhance the dissolution rate of Rivaroxaban by delivering the drug as a liquisolid compact. Liquisolid compacts were prepared using microcrystalline cellulose as the carrier and aerosil 200 as the coating material (R).PEG 400 was used as the liquid vehicle by studying the effect of the variable for response with the help of Box-Behnken design (BBD). A total of 17 formulations were prepared by altering the proportion of microcrystalline cellulose, aerosil 200 and PEG 400 by direct compression technique. The drug concentration was kept constant in all formulations at 50mg. Optimization was carried out using Box–Behnken design by selecting liquid load factor, amount of coating material, and amount of magnesium oxide as independent variables; drug content and angle of repose were considered as dependent variables.The Fourier transform infrared (FTIR) and differential scanning calorimetry (DSC) studies revealed that there was no possible interaction between drug and tablet excipients. Prepared rivaroxaban liquisolid tablets were evaluated for thickness, hardness, weight variation, friability test, drug content, in-vitro dissolution studies, disintegration time, and stability studies. The optimized formulation yielded the response values, which were very close to the predicted values. Stability Study of optimized formula performed for 180 days at 30±2°C and 65±5% RH and 40⁰C±2 ⁰C and 75 ±5% RH

.Stability study performed on such parameters Color, Shape and Appearance. As a result there was no change seen at the end of the study. At the end drug content study of optimized formula performed and result shows that it was a stable formulation which was not degraded at different temperature and stable. In-vivo carrageenan induced antithrombic activity was performed on theSwiss albino rat (190-195±5gm). The results of our study suggest that formulation has significant effects against thrombosis. The mean length of the tail infracted region in the formulation- administered and heparin treated rat was shorter than that in the control rat. Typically, thrombosis occurs because of platelet aggregation or vasoconstriction, although platelet aggregation caused by cyclooxygenase inhibition has little or no effect on carrageenan-induced thrombosis in rat tails.