DEVELOPMENT AND EVALUATION OF COMPRESSION COATED TIMED-RELEASE TABLETS OF CANDESARTAN CILEXETIL FOR CHRONOTHERAPY OF HYPERTENSIONAbstract
Chronotherapy involves the release of drug to the systemic circulation based on the circadian rhythm associated with the pathophysiology of a disease. Candesartan Cilexetil, an anti-hypertensive drug, is formulated to contribute to the chronotherapy of hypertension. Solubility study of the drug (BCS Class II) in various media indicated maximum solubility in pH 6.8 sodium phosphate buffer containing 1% SLS. Solid dispersion of Candesartan Cilexetil with PVP K30 was prepared by melt dispersion. Core tablet containing solid dispersion equivalent to 16mg Candesartan Cilexetil was prepared by direct compression. The % dissolution efficiency (DE60) of the pure drug was 31.05% and increased for the solid dispersion to 56%. Compression coating was applied to this core tablet by direct compression using release rate retardants HPMC K15M and Eudragit S100 in various proportions to give timed-release. In-vitro drug release test carried out in 0.1 N HCl for the first 2 h and pH 6.8 buffer containing 1% SLS for next 8 hrs showed formulation F4 containing 75 % of HPMC K15M and 25% Eudragit S100 as coat, to release only 5% drug in first 6 hrs, 85% release by 8th hr and 100% drug release by 10th h of study. Thus compression coated timed release tablets of Candesartan Cilexetil when administered at night will release the drug after 6 h lag time, i.e., during the early morning hours when the blood pressure will be higher and contribute to chronotherapy of hypertension. F4 has been evaluated for stability for 2 months at 40°C/75%RH and was found to be stable.
B. L. R. Madhavi * and K. Deepika
Department of Pharmaceutics, RBVRR Women’s College of Pharmacy, Barkatpura, Hyderabad, Andhra Pradesh, India.
03 April 2014
25 May 2014
17 July 2014
01 October 2014