FORMULATION AND EVALUATION OF CHRONOMODULATED DRUG DELIVERY SYSTEM CONTAINING CAPTOPRIL AND HYDROCHLOROTHIAZIDE

ABSTRACT Blood pressures displays circadian rhythm. The objective of present study was to develop chronomodulated drug delivery system containing Captopril and Hydrochlorothiazide to achieve extended retention in upper gastro intestinal tract to enhance absorption and bioavailability. Captopril mucoadhesive microspheres were prepared by emulsification method using sodium alginate and guar gum polymers whereas Hydrochlorothiazide floating microspheres were prepared by non-aqueous solvent evaporation method using ethyl cellulose and hydroxyl propyl methyl cellulose K15 polymers in various ratios. Fourier-transform infrared spectroscopy study showed that drug and polymers were compatible with each other. The effects of polymer concentration on drug release profile were investigated. From the drug and excipients compatibility studies it was confirmed that the drug and excipients used weren’t have any interactions. Microspheres obtained were evaluated for percentage yield, micromeritics studies, percentage mucoadhesion, percentage buoyancy, percentage entrapment efficiency, in-vitro percentage drug release after 10 hours, in-vitro kinetic release studies and surface morphology. Formulation M3 (1:3, sodium alginate) showed highest drug entrapment efficiency 72.54 %, 93.09 % mucoadhesion and 74.38 % drug release after 10 hours. Formulation F12 (1:4, ethyl cellulose and hydroxyl propyl methyl cellulose K15) showed higher drug entrapment efficiency 85.75 %, percentage buoyancy 80.42 % and 61.02 % drug release after 10 hours. Scanning electron microscopy showed that microspheres were spherical in shape. In-vitro release studies showed that formulation observed Zero-order and Peppas (Case II transport) pattern. Better results were observed, thereby improving the bioavailability and treating hypertension effectively due to prolong release of drug in stomach. KEYWORDS: Chronomodulated drug delivery system, Captopril, Hydrochlorothiazide, Mucoadhesive microsphere, Floating microsphere