Studies On Preparation Of Captopril Sustained-release Capsules

Captopril, an angiotensin-converting enzyme inhibitor, has been widely used to treat hypertension and congestive heart failure. Its biological half-life is relatively short ( about 1.9 h ), its market tablet was dosed clinically 3 ( 4 times per day. The efficacy duration time was 6 h ( 8 h when 37.5 mg ( 75 mg captopril was given. The maximum concentration of captopril was 600 ng/ml in plasma after a single oral administration of 50 mg captopril, while the effective concentration was 50 ng/ml. The fluctuation of blood concentration may induce some adverse drug reactions, eg: giddiness, headache, functional digestive disorders. It is necessary to develop sustained-release preparation of captopril. The study was aimed to develop a captopril sustained-release capsules which would reduce dosing frequency and narrow the fluctuation of blood concentration of captopril.The absorption peak of captopril in aqueous solvent within ultraviolet extent lie on the edge of the ultraviolet extent, so it is unsuitable for the direct determination of the content and dissolution. RP-HPLC was used to detect the captopril concentration in sustained-release capsules. The differential spectrophotometric method was utilized for assaying release of captopril sustained-release capsules according to the absorption of captopril varied with different solvent system.Captopril pellets was prepared with microcrystalline cellulose as dilute matrix and 3% HPMC solution as adhesive agent by centrifugal granulation technology. The core pellets including drug were evaluated with index signs of size distribution, roundness and friability. The pellets were coated with Eudragit NE30D aqueous dispersion. Drug release rate was used to evaluate the formulation and preparation conditions. The release property and mechanism were studied by describing the drug release curve using different kinetics (zero-order, first-order, Higuchi square-root ). The research revealed that the coated pellets exhibited a marked sustained-release property, the drug release profiles in vitro followed first-order kinetic.Captopril sustained-release pellets did not find distinct changes in appearance and dissolution, when they were exposed to high temperature, high humidity, strong light respectively. While the content and relative substances changed significantly.