FABRICATION, OPTIMIZATION AND EVALUATION OF CHRONOTROPIC DRUG DELI-VERY SYSTEM OF CAPTOPRIL

The present investigation was based on the development and evaluation of chronotropic capsules for hypertension treatment. Captopril has ACE inhibitor action to prevent the circadian rhythm related to hypertension. The solubility of captopril in the GI tract was pH-dependent i.e., captopril soluble only at 1.2 pH, show better stability, and absorbed in the upper part of the gastrointestinal tract. Captopril has 1-2 h half-life (t_1/2) and 3.7 pKa value. For the optimization of formulation 3² factorial designs was used and in these methods, two independent variables at three levels were selected. The direct compression method was used for the preparation of pulsincap plugs.  The dissolution profile of formulated batch F1 to F9 at the end of 9 h was found in the range of 92.50 to 99.60% in different pH of phosphate buffer.  From the results, it was found that formulation F5 was shown the most similar dissolution profile because the similarity value was found to be above 90%. The swelling index was found higher in formulation F5 and time for erosion was 78 minutes for F5 formulation. Statistically, the formulation was optimized, and P and R² values for the response variable (time of erosion of plug) were observed 0.0152 & 0.7130, respectively. The second response variable % drug release showed the P & R² values as 0.0016 & 0.8225 respectively. P-value and R²denote that model was significant for the formulation in the correspondence of major response variables.