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OPTIMIZATION OF TELMISARTAN TABLET FORMULATION
ABSTRACT: The objective of the present study is optimization of telmisartan tablet formulation employing βCD, Primojel, and Tween 80 by 23 factorial design to achieve NLT 85% dissolution in 10 min. Eight telmisartan tablet formulations were prepared using selected combinations of the three factors as per 23 factorial design. Telmisartan tablets were prepared by direct compression method and were evaluated. Telmisartan tablet formulations Fb and Fbc disintegrated rapidly in 20 and 40 seconds and gave very rapid dissolution of telmisartan, 96.1% and 95.8% in 10 min respectively. The increasing order of dissolution rate (K1) observed with various formulations was Fc< F1< Fac< Fa< Fabc< Fab< Fbc< Fb. The polynomial equation describing the relationship between the response,  percent drug dissolved in 10min (Y) and the levels of βCD (X1) , Primojel (X2)  and Tween 80 (X3) based on the observed results is  Y = 55.327 + 3.613(X1) + 35.072(X2) – 9.182(X1 X2) – 3.757(X3) – 3.317(X1 X3) + 2.06(X2 X3) + 1.765(X1 X2 X3). Based on the above equation, the formulation of optimized telmisartan tablets with NLT 75% dissolution in 10 min require βCD at 1:3.5 ratio of drug: βCD, Primojel at 27.84% of drug content, and Tween 80 at 1% of drug content. The optimized telmisartan tablet formulation gave 85.85% dissolution in 10min fulfilling the target dissolution requirement.
Keywords:
Telmisartan tablets, Optimization, β-cyclodextrin, Primojel, Tween 80, Factorial Design
INTRODUCTION: About 95% of all new potential therapeutic drugs (APIs) exhibit low and variable oral bioavailability due to their poor aqueous solubility at physiological pH and consequent low dissolution rate. These drugs are classified as class II drugs under BCS with low solubility and high permeability characters. These BCS class II drugs pose challenging problems in their pharmaceutical product development process. 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. Because of poor aqueous solubility and dissolution rate it poses challenging problems in its tablet formulation development. It needs enhancement in the dissolution rate in its formulation development.
Several techniques 1 such as micronisation, cyclodextrin-complexation, use of surfactants, solubilizers and super disintegrants, solid dispersion in water soluble and water dispersible carriers, microemulsions and self emulsifying micro and nano disperse systems have been used to enhance the solubility, dissolution rate and bioavailability of poorly soluble BCS class II drugs. Among the various approaches cyclodextrin complexation and use of superdisintegrants such as crosspovidone and sodium starch glycolate (Primojel) are simple industrially useful approaches for enhancing the dissolution rate of poorly soluble drugs in their formulation development.
Surfactants such as SLS, Tween 80 are also used for enhancing the solubility of poorly soluble drugs in formulation development. β-cyclodextrin (βCD), Primojel and Tween 80 were tried alone and in combination as per 23 factorial study  for enhancing the dissolution rate of telmisartan in its formulation development. Formulation of telmisartan tablets with NLT 85% dissolution in 10 min employing Primojel, βCD and Tween 80 was optimized .