OPTIMIZATION OF βCD AND SUPERDISINTEGRANT LEVELS FOR FORMULATION OF VALSARTAN IR TABLETS BY 22 FACTORIAL DESIGN

Abstract

Valsartan, 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. Complexation with β-cyclodextrin (βCD) and use of superdisintegrant (crosspovidone or Primojel) are tried for
enhancing the dissolution rate of valsartan tablets. The objective of the present study is to optimize the βCD and superdisintegrant
levels for formulation of valsartan IR tablets by 22 factorial design to achieve NLT 85% dissolution in 15 min. A total of eight
valsartan IR tablet formulations were prepared using selected combinations of the two factors as per 22 factorial design.
Valsartan tablets were prepared by direct compression method and were evaluated for drug content, hardness, friability,
disintegration time and dissolution rate characteristics. The dissolution rate (K1) values were analysed as per ANOVA of 22
factorial design to find the significance of the individual and combined effects of the two factors (βCD and superdisintegrant)
involved on the dissolution rate of valsartan tablets formulated.The individual and combined effects of βCD and superdisintegrant
(crosspovidone or Primojel) on the dissolution rate (K1) of valsartan tablets are highly significant (P<0.01).Valsartan tablets
formulated employing superdisintegrant (crosspovidone or Primojel) at a level of 30% of drug content and βCD in 1:1 ratio of
drug: βCD (Fa) disintegrated rapidly within 30 seconds and gave very rapid dissolution of valsartan fulfilling the target dissolution
of NLT 85% in 15 min. Higher levels of βCD and lower levels of superdisintegrants gave low dissolution rates with both the
superdisintegrants. The polynomial equation describing the relationship between the response i.e. percent drug dissolved in 15min
(Y) and the levels of superdisintegrant (X1) and βCD (X2) based on the observed results is Y = 42.42+27.795 (X1) -12.705 (X2) -
17.09 (X1 X2) in the case of formulations based on βCD and crosspovidone and Y = 39.603+24.702 (X1) -7.652 (X2) -13.35 (X1
X2) in the case of formulations based on βCD and Primojel. βCD in 1:1 ratio of drug: βCD and superdisintegrant (crosspovidone
or Primojel) at a level of 30% of drug content are the optimized levels for formulation of valsartan IR tablets with dissolution of
NLT 85% in 15 min.