Abstract

FORMULATION AND EVALUATION OF DILTIAZEM FLOATING TABLETS EMPLOYING A NEW MODIFIED STARCH – OPTIMIZATION BY 23 FACTORIAL DESIGN

Sailaja Gunnam* and K. P. R. Chowdary

ABSTRACT

The objective of the present study is optimization of diltiazem floating tablet formulation by 23 factorial design. Floating tablets of diltiazem (60 mg) were formulated employing Cross linked starch-urea, a new modified starch (50 %) as matrix forming polymer, sodium bicarbonate as gas generating agent and beeswax and ethyl cellulose as floating enhancers. Diltiazem has short biological half-life of about 3.5 h and is rapidly eliminated. It is favourably absorbed from stomach and the oral bioavailability is 40% in humans. Diltiazem floating tablets were formulated as per 23 factorial design. The three factors involved in the 23 factorial design are sodium bicarbonate (Factor A), beeswax (Factor B) and ethyl cellulose (Factor C). The two levels of sodium bicarbonate (Factor A) are 10 and 20 %, the two levels of beeswax (Factor B) are 2 % and 5 % and the two levels of ethyl cellulose (Factor C) are 5% and 10%. Eight diltiazem floating tablet formulations were prepared employing selected combinations of the levels of the three factors as per 23 factorial design. All the floating tablets prepared were evaluated for drug content, hardness, friability, disintegration time, floating lag time, floating time and drug release characteristics. Diltiazem floating tablets prepared as per 23 factorial design were non-disintegrating in water and aqueous acidic (pH 1.2) and alkaline (pH 7.4) fluids and were of good quality with regard to drug content, hardness, friability and suitable for controlled release. The individual effects of sodium bicarbonate (Factor A) and ethyl cellulose (Factor C) and their combined effect (AC) on the floating lag time were significant (P < 0.05).Whereas the individual effect of bees wax (Factor B) and all other combined effects of the three factors involved were not significant in influencing floating lag time of the tablets. Formulations Fab, Fac and Fabc exhibited excellent floating over 12-14 h with a floating lag time in the range 15-32 seconds. Higher levels (20 %) of sodium bicarbonate gave shorter floating lag time. Diltiazem release from the floating tablets prepared except formulation Fa was slow and spread over 12 h and dependent on the composition of the tablets. Drug release from formulation Fa was very rapid. Diltiazem release from the floating tablets was by non-fickian diffusion mechanism in all the cases except Fa . In the case of formulation Fa that gave rapid release of drug fickian diffusion was the drug release mechanism. Optimization of diltiazem floating tablet formulation was done taking floating lag time as the parameter for optimization. For optimization, floating lag time was taken as response (Y) and level of sodium bicarbonate as (X1), level of bees wax as (X2) and level of ethyl cellulose as (X3). The polynomial equation describing the relationship between the response, Y and the variables, X1 , X 2 and X3 based on the observed data was found to be Y = 6.126 - 5.619 (X1) + 0.774 (X2) – 0.891 (X1 X2) -0.246 (X3) + 0.254(X1 X3) – 0.059 (X2 X3) + 0.191(X1 X2 X3) Based on the polynomial equation developed, the optimized diltiazem floating tablet formulation with a floating lag time of 20 seconds or 0.33 min could be formulated employing sodium bicarbonate (100mg/tablet), beeswax (17.5mg/tablet) and ethyl cellulose (37.5mg/tablet). The optimized formulation (Fopt) exhibited a floating time of 14 h with a lag time of 22 seconds fulfilling the target floating lag time set indicating validity of the optimization technique employed. Formulations Fopt and Fac prepared exhibited excellent floating characteristics (floating over 13-14h with a lag time of 22 and 30seconds respectively) and good sustained release of diltiazem over 12 h. Formulations Fopt and Fac are considered as the best floating tablet formulations of diltiazem suitable for b.i.d administration.

Keywords: Floating tablets, Diltiazem, Optimization, Factorial design, Sustained release.