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IN VITRO AND IN VIVO PHARMACOKINETIC EVALUATION OF VALSARTAN TABLETS: OPTIMIZATION BY FACTORIAL DESIGN 2³

Ch. Tarakaramaraoa*, K . P. R. Chowdaryb and P. Rajeswara Raoc

a Department of Pharmaceutical Technology, Sri Venkateswara College of Pharmacy, Etcherla, Srikakulam- 532410, India

b Chairman, BOS in Pharmacy, JNTUK, Kakinada- 533003, India

c AU College of Pharmaceutical Sciences, Andhra University, Visakhapatnam - 530003, India

* For Correspondence: e-mail: tarak.pharm60@gmail.com


ABSTRACT

Valsartan, a widely prescribed anti hypertensive drug, belongs to class II under BCS classification and needs enhancement in the dissolution rate in its formulation development. The objective of the present study was optimization of Valsartan tablet formulation with NLT 85% dissolution in 10 min employing βCD, Crospovidone and SLS by 23 factorial design. The optimized valsartan tablets developed were evaluated for in vitro dissolution and in vivo pharmacokinetics. Eight valsartan tablet formulations employing selected combinations of the three factors i.e., βCD, Crospovidone and SLS as per 23 factorial design were formulated, prepared by direct compression method and evaluated by in vitro and in vivo methods. Valsartan tablet formulations Fb and Fbc disintegrated rapidly within 45 sec and gave very rapid dissolution of valsartan, 100% in 10 min. Higher levels of βCD and lower levels of Crospovidone gave low dissolution rates of valsartan tablets. The increasing order of dissolution rate (K1) observed with various formulations was Fb = Fbc > Fab > Fabc > Fa > Fac > F1 > Fc. The polynomial equation describing the relationship between the response i.e. percent drug dissolved in 10 min (Y) and the levels of β CD (X1) ,Crospovidone (X2) and SLS (X3) based on the observed results is Y = 60.05 + 5.34 (X1) +33.88 (X2) –8.95 (X1 X2) -3.18 (X3) -2.38 (X1 X3) + 2.80 (X2 X3) + 1.95 (X1 X2 X3).based on the above polynomial equation, the optimized valsartan tablet formulation with NLT 85% dissolution in 10 min (Fopt1) could be formulated employing βCD at 1:3 ratio of drug: β CD, Crospovidone at 26.31% of drug content , and SLS at 1% of drug content. The optimized valsartan tablet formulation (Fopt1) gave 85.86 % dissolution in 10 min, fulfilling the target dissolution set. In the pharmacokinetic evaluation, the biological half – life (t ½)was found to be 5.06h and 4.66 h, respectively, following the administration of optimized valsartan tablets formulated (Fopt2) and market product. With both the two products tested valsartan was absorbed rapidly and peak concentration is achieved in 1 h. The absorption rate constant (Ka) was 2.275 h-1 and 1.409 h-1 respectively with Fopt2 and market product. The relative bioavailability (bA) of valsartan from the Fopt2 formulation was 105.7 % when compared to market product (100%).The optimized valsartan tablets formulated employing βCD, Crosspovidone and SLS (Fopt2) are comparable to the market product with regard to in vivo performance.

Year 2020 | Volume No. 57 | Issue No.11 | Page No. 15-21
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