Abstract

OPTIMIZATION OF OLMESARTAN TABLET FORMULATION BY 22 FACTORIAL STUDY

K. P. R. Chowdary*, K. Ravi Shankar and P. Suneel Kumar

ABSTRACT

Olmesartan, a widely prescribed anti-hypertensive drug belongs to class II under BCS classification and exhibits 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. In the case of poorly soluble drugs the excipients in tablet formulation significantly influence dissolution rate and consequently bioavailability of the drug requiring a rational selection of binder and disintegrant combination. The objective of the study is to optimize olmesartan tablet formulation by 22 factorial design for selecting the best combinations of binder and disintegrant giving fast dissolution of the drug, olmesartan. Much variations were observed in the disintegration and dissolution characteristics of the olmesartan tablets prepared employing various combinations of binder (Factor A) and disintegrant (Factor B) as per 22 factorial design. Olmesartantablet formulations Fb (tablets prepared employing lactose, acacia and Primojel) and F1(tablets prepared employing lactose, acacia and potato starch) disintegrated rapidly within1 min 10 sec. ANOVA of dissolution rate (K1) values indicated that the individual and combined effects of the two factors, binder (Factor A) and disintegrant (Factor B) in influencing the dissolution rate of olmesartan tablets are highly significant (P < 0.01).Among all, formulation Fb (tablets prepared employing lactose, acacia and Primojel) and F1 (tablets prepared employing lactose, acacia and potato starch) gave higher dissolution rates and DE30 values.The increasing order of dissolution rate (K1) observed with various formulations was Fb>F1> Fa>Fab. Thus, the results of the present study indicated that combinations of (i) lactose, acacia and Primojel, (ii) lactose, acacia and potato starch are the best combinations of diluent, binder and disintegrant and hence these combinations are recommended for formulation of olmesartan tablets giving rapid and higher dissolution of olmesartan, a BCS class II drug.

Keywords: Formulation development, Optimization, Olmesartan, Binder, Disintegrant, Factorial design.