Abstract

FORMULATION OF TELMISARTAN TABLETS EMPLOYING βCD, CROSPOVIDONE, POLOXAMER - OPTIMIZATION BY 23 FACTORIAL DESIGN

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

Abstract

Telmisartan, 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 β-cyclodextrin (βCD), crospovidone and Poloxamer188 were tried to enhance the dissolution rate of telmisartan in its tablet formulation development. The objective of the study is to optimize telmisartan tablet formulation by 23 factorial design to achieve NLT 85% dissolution in 10 minutes. For optimization of Telmisartan tablets as per 23 factorial design the βCD, crospovidone and Poloxamer188 are considered as the three factors. The two levels of the factor A (βCD) are 1:1 and 1:5 ratio of drug: βCD, the two levels of the factor B (crospovidone) are 2% and 30% of drug content and the two levels of factor C (Poloxamer188) are 0% and 2% of drug content. Eight Telmisartan tablet formulations employing selected combinations of the three factors i.e. βCD, crospovidone and Poloxamer188 as per 23 factorial design were formulated. The tablets were prepared by direct compression method and were evaluated. Telmisartan tablet formulations Fb and Fbc disintegrated rapidly with in 1min and gave very rapid dissolution of telmisartan, above 99% in 10 min.Higher levels of βCD and lower levels of crospovidone gave low dissolution rates of telmisartan tablets. The increasing order of dissolution rate (K1) observed with various formulations was Fbc > Fb > Fab >F abc> Fa >Fac> F1>Fc.The polynomial equation describing the relationship between the response i.e. percent drug dissolved in 10min (Y) and the levels of βCD (X1) , crospovidone (X2) and Poloxamer188 (X3) based on the observed results is Y = 59.52 + 4.05(X1) + 34.9(X2) – 9.22(X1 X2) – 3.82(X3) - 3.0(X1 X3) + 2.45(X2 X3) + 1.52 (X1 X2 X3). Based on the above polynomial equation, the optimized telmisartan tablet formulation with NLT 85% dissolution in 10 min could be formulated employing βCD at 1:3 ratio of drug: βCD, crospovidone at 26.22% of drug content and Poloxamer188 at 1% of drug content. The optimized telmisartan tablet formulation gave 86.15% dissolution in 10min fulfilling the target dissolution set. Hence optimization by 23 factorial design could be used to formulate telmisartan tablets with the desired dissolution i.e., NLT 85% in 10 min.

Keywords: Optimization, Telmisartan tablets, Factorial design, ? Cyclodextrin, Crospovidone, Poloxamer188.