Abstract

OPTIMIZATION OF TELMISARTAN TABLET FORMULATION BY 23 FACTORIAL DESIGN

K.P.R. Chowdary* and M. Gowthami

ABSTRACT

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. 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 diluent, binder and disintegrant combination. The objective of the study is to optimize telmisartan tablet formulation by 23 factorial design for selecting the best combinations of diluent, binder and disintegrant giving fast dissolution of the drug, telmisartan. Much variations were observed in the disintegration and dissolution characteristics of the telmisartan tablets prepared employing various combinations of binder (factor A), disintegrant (factor B) and diluent (factor C) as per 23 factorial design. ANOVA of K1 values indicated that the individual and combined effects of the three factors in influencing the dissolution rate of tablets are highly significant (P < 0.01) except the individual effect of DCP and combined effects of (Primojel – DCP) and (PVP – Primojel – DCP). All the telmisartan tablets formulated employing lactose as diluent disintegrated rapidly within 1 min 40 sec. Tablet formulation Fa disintegrated vary rapidly within 35 sec. All tablets formulated employing DCP as diluents disintegrated rather slowly within 2- 4 min. Tablets formulated employing lactose as diluent gave rapid and higher dissolution of telmisartan than those formulated with DCP. Among all, formulation Fa (tablets prepared employing lactose, PVP and potato starch), 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 Fa> Fb >F1>Fab>Fac> Fbc=F abc>Fc. All formulations except Fc fulfilled the official dissolution rate test specification of NLT 75% in 30 min.Thus, the results of the present study indicated that combinations of i) lactose, PVP and potato starch (ii) lactose, acacia and Primojel and (iii) lactose, acacia and potato starch are the best combinations of diluent, binder and disintegrant and hence these combinations are recommended for formulation of telmisartan tablets giving rapid and higher dissolution of telmisartan, a BCS class II drug.

Keywords: Formulation development, Optimization, Telmisartan, Diluent, Binder, Disintegrant, Factorial design.