Integrated QbD Approach for the Development of Liquisolid Compact of Apixaban for Improvement of Solubility and Dissolution Rate

Apixaban is a novel oral anticoagulant widely recommended for the prevention and treatment of strokes and blood clots suffering from nonvalvular atrial fibrillation by suppressing factor Xa. Moreover, it is also useful in minimizing deep vein thrombosis and pulmonary embolism in patients after knee replacement surgery. The usefulness of Apixaban is circumscribed due to poor solubility and less bioavailability. The recent research aimed to develop an improved formulation of Apixaban by progressing the solubility and dissolution rate. The solubility estimation was carried out in numerous solubilizers and the highest solubility was reported in PEG 200. The compatibility was checked with FTIR, DSC, and crystalline nature with XRD. The optimization design involved Box-Behnken involving the concentration of MCC 102 (X1), Aerosil 200 (X2) and cross povidone (X3) as independent factors, whereas disintegration time (Y1) and dissolution release (Y2) were chosen as dependent factors. The ANOVA showed polynomial quadratic equations with p-values of 0.0028 and 0.0154 for the disintegration time and dissolution release correspondingly. The optimized batch F6 showed superior flowing characteristics and minimal quantity with maximum benefits. The tiniest disintegration time of 2.40 min and dissolution of 99.35 % was attained with batch F6. The cumulative drug released from this optimized batch was observed within 30 min. The marked improvement in the solubility and dissolution rate of Apixaban was achieved through the Liquisolid Compact Technique which facilitates greater bioavailability and therapeutic efficacy.