Abstract

FORMULATION OF CARVEDILOL TABLETS EMPLOYING SOLID DISPERSIONS IN MCC PH102 AND POLOXAMER188 AS PER 22 FACTORIAL DESIGN

V. Ramesh*, Rukesh Kumar Jat and K. P. R Chowdary

ABSTRACT

Carvedilol, a widely prescribed anti hypertensive drug belongs to class II under BCS classification and exhibit low and variable oral bioavailability due to its poor aqueous solubility. It needs enhancement in the dissolution rate in its formulation development to derive its maximum therapeutic efficacy. In the present study solid dispersion in micro crystalline cellulose (MCC) and Poloxamer 188 were tried alone and in combination to enhance the dissolution rate of Carvedilol in its tablet formulation development. The objective of the present study is to optimize Carvedilol tablet formulation by 22 factorial design using solid dispersions in MCC PH102 (a water dispersible excipient) and Poloxamer188 (surfactant) to achieve NLT 85% dissolution in 10 minutes. For optimization of Carvedilol tablets as per 22 factorial design using solid dispersions, the MCC PH102 and Poloxamer188 are considered as the two factors. The two levels of the factor A (MCC) are 1:1 and 1:5 ratio of drug: MCC PH102 and the two levels of the factor B (Poloxamer188) are 1% and 5% of drug content. Four Carvedilol tablet formulations employing selected combinations of the two factors i.e. MCC PH 102 and Poloxamer188 as per 22 factorial design were formulated. Solid dispersions of Carvedilol in combined carriers were initially prepared and were used to prepare the tablets. The tablets were prepared by direct compression method and were evaluated. Carvedilol tablet formulations Fa disintegrated rapidly with in 30 sec and gave very rapid dissolution of Carvedilol, 100% in 10 min. The increasing order of dissolution rate (K1) observed with various formulations was Fa > Fab > Fb >F1. The polynomial equation describing the relationship between the response, Y and the variables, X1 and X2 based on the observed data was found to be Y = 61.95 + 31.07(X1) + 8.92(X2) – 10.90(X1 X2). Based on the above polynomial equation, the optimized Carvedilol tablet formulation with NLT 85% dissolution in 10 min could be formulated employing MCC at 1: 4.5 ratio of drug: MCC PH102, and Poloxamer188 at 3% of drug content. The optimized Carvedilol tablet formulation gave 85.45% dissolution in 10min fulfilling the target dissolution set. Hence optimization by 22 factorial design employing solid dispersions in MCC PH102 and Poloxamer188 could be used to formulate Carvedilol tablets with the desired dissolution i.e., NLT 85% in 10 min.

Keywords: Optimization, Carvedilol tablets, Factorial design, Solid dispersion, MCC PH102, Poloxamer188.