Diltiazem hidroklorür yüklenmiş mikroküreler ve modifiye salım yapan tablet formülasyonlarının geliştirilmesi
Özet
Microspheres Loaded with Diltiazem Hydrochloride and Development of their Modified Release Tablet Formulations Diltiazem hydrochloride is a drug that has been widely used in the chronical treatment of various cardiovascular diseases. In clinical studies, it is preferred to be used at high doses of 90 mg, twice a day or 60 mg, three times a day. Basically in our study, it was aimed to prepare the modified release tablet formulations containing microspheres loaded with diltiazem hydrochloride at an amount of 180 mg to apply once a day, which is not available in Turkish drug market yet. For this purpose, due to the physicochemical properties of the drug, w/o emulsion solvent evaporation method was used for preparing microspheres. Different microsphere formulations were prepared by using the polymers, ethylcellulose and Eudragit®RS 100; the emulsifiers, Span 80 and aluminum tristearate and a plastizer, triethylcitrate. In the development of microsphere formulations of the model drug, the effective process parameters which provide the release of the drug for 24 hours from the modified release tablet formulations containing microspheres were investigated. The production yield, process efficacy, particle size and size distribution, morphological properties, in vitro dissolution rate and kinetics of the microsphere formulations were evaluated and the most suitable three microsphere formulations were selected for tablet dosage form. For the tabletting of the microsphere formulations, different types of direct tabletting agents such as Kollidon®SR, Compritol®888 ATO, Ludipress® and Cellactose®80 were used. In vitro dissolution rate studies were performed on the prepared tablets in different pH dissolution media. The profiles obtained from the in vitro dissolution rate studies were compared with the profiles obtained from the reference product which is in the micropellet form in a hard gelatin capsule and available in international drug markets. As a result, by using different direct tabletting agents, different tablet formulations were developed from the microsphere formulations prepared with different excipients. Eventually, tablet formulations of the model drug were achieved which maintained the drug release for 24 hours, while showing the profiles that fitted to the target profile.Key Words : Diltiazem hydrochloride, microsphere, modified release systems, solvent evaporation method, tablet.