Abstract

STUDIES ON FORMULATION OF DILTIAZEM TABLETS USING ?CD, CROSCARAMELLOSE SODIUM AND SODIUM DODECYL SULFATE-OPTIMIZATION BY 23 FACTORIAL DESIGN

Ch. Saibabu*, Dr. K. Thejomoorthy and Rakesh Kumar Jat

ABSTRACT

Diltiazem, 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 to derive its maximum therapeutic efficacy. In the present study β-cyclodextrin (βCD), croscarmellose sodium and Sodium dodecyl sulphate were tried to enhance the dissolution rate of diltiazem in its tablet formulation development. The objective of the study is to optimize diltiazem tablet formulation by 23 factorial design to achieve NLT 85% dissolution in 15 minutes. For optimization of Diltiazem tablets as per 23 factorial design the Cyclodextrin (βCD), croscarmellose sodium and Sodium dodecyl sulphate are considered as the three factors. The six levels of the factor A (βCD) are ratio of drug: βCD, the eight levels of the factor B (croscarmellose sodium) and the eight levels of factor C (Sodium dodecyl sulfate). Eight Diltiazem tablet formulations employing selected combinations of the three factors i.e. βCD, croscarmellose sodium and Sodium dodecyl sulphate as per 23 factorial design were formulated. The tablets were prepared by direct compression method and were evaluated. The physical parameters of the Diltiazem tablets evaluated and hardness of the tablets was in the range 96-132 N. Weight loss in the friability test was less than 0.04% in all the cases. Diltiazem content of the tablets prepared was within 100±3 %. Much variations were observed in the disintegration and dissolution characteristics of the Diltiazem tablets prepared. The disintegration times were in the range 3 min 02 sec to 4 min 12 sec. Dissolution rate of diltiazem tablets prepared was studied in phosphate buffer pH 5.8. Dissolution of Diltiazem from all the tablets prepared followed first order kinetics with coefficient of determination (R2) values above 0.942. The first order dissolution rate constant (K1) values were estimated from the slope of the first order linear plots. Much variations were observed in the dissolution rate (K1) and DE30 values of the tablets prepared due to formulation variables. ANOVA of K1 values indicated that the individual and combined effects of the three factors, βCD, croscarmellose sodium and Sodium dodecyl sulphate except F020 (Combined effect of croscarmellose sodium and Sodium dodecyl sulphate) and F020 (Combined effect of βCD, croscarmellose sodium and Sodium dodecyl sulphate) in influencing the dissolution rate of Diltiazem tablets are highly significant (P < 0.01). Diltiazem tablet formulations F018 and F020 gave very rapid dissolution of Diltiazemthan others. These tablets (F018 and F020) gave above 90% dissolution in 15min. Higher levels of βCD and lower levels of croscarmellose sodium gave low dissolution of Diltiazem tablets. The increasing order of dissolution rate (K1) observed with various formulations was F014 > F008 > F011 >F016> F017 >F018> F020. The optimized Diltiaazem tablet formulation gave 91% dissolution in 15 min fulfilling the target dissolution set. Hence optimization by 23 factorial design could be used to formulate diltiazem tablets with the desired dissolution i.e., NLT 85% in 15 min.

Keywords: Optimization, Diltiazem tablets, Factorial design, ? Cyclodextrin, Croscarmellose sodium, Sodium dodecyl sulphate.