Abstract

OPTIMIZATION OF IRBESARTAN TABLET FORMULATION BY 22FACTORIAL STUDY

K. P. R. Chowdary*, K. Ravi Shankar and Ch. Chandrasekhar

Abstract

Irbesartan, 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. 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 irbesartan tablet formulation by 22 factorial designs for selecting the best combinations of binder and disintegrant giving fast dissolution of the drug, irbesartan. Much variations were observed in the disintegration and dissolution characteristics of the irbesartan tablets prepared employing various combinations of binder (factor A) and disintegrant (factor B) as per 22 factorial design. All the irbesartan tablets formulated disintegrated rapidly within 1 min 25 sec except formulation Fa which disintegrated in 6 min 10 sec. The results of ANOVA of K1 values indicated that the individual effect of binder (Factor A) and combined effects of binder and disintegrant (Factor AB) are highly significant (P < 0.01). Among all, formulation F1 (tablets prepared employing lactose, acacia and potato starch) and Fb (tablets prepared employing lactose, acacia and Primojel) gave higher dissolution rates and DE30 values. The increasing order of dissolution rate (K1) observed with various formulations was F1>Fb> Fab>Fa. Formulations F1 and Fb, gave 93.07 and 93.85 % dissolution in 20 min respectively fulfilling the official dissolution rate test specification. Thus, the results of the present study indicated that combinations of (i) lactose, acacia and potato starch, (ii) lactose, acacia and Primojel are the best combinations of diluent, binder anddisintegrant and hence these combinations are recommended for formulation of irbesartan tablets giving rapid and higher dissolution of irbesartan, a BCS class II drug.

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