Hemen Salım Sağlayan Kandesartan Sileksetil Tablet Formülasyonuna Tasarımla Kalite Uygulaması

Abstract

It was investigated a stable formulation development, process understanding and controlling of immediate release Candesartan Cilexetil 32 mg tablet by using QbD approach. Candesartan Cilexetil is a drug substance indicating chemical stability problem in tablet dosage form and having low solubility property. Stability protective property and stabilizing mechanism of PEG 4000 on Candesartan Cilexetil were identified with drug substance-polymer interaction studies by using UV spectrofotometry, DSC and FTIR spectroscopy methods. In consideration of formulation development and manufacturing process determination studies, preformulation and DOE studies were performed. With DOE studies, dissolved drug substance from tablet could be predicted for determined target levels of CMAs which are PEG 4000, starch maize, carmellose calcium, HPC and water formulation inactive ingredients. Thus, in developed tablet dosage form stability and dissolution properties of Candesartan Cilexetil could be controlled. Understanding the formulation and process, ensured the TPQP without testing Candesartan Cilexetil 32 tablet product. It was also foreseen that stable tablet dosage form can be developed which degradates inside the acceptable limit in accelerated stability condition. Developed Candesartan Cilexetil 32 tablet can be stored inside primary package of HDPE bottle closed with childproof cap in 25 ºC (77 ºF) storage condition.