Controlled Release of Propranolol Hydrochloride and Indomethacin from Hollow Type Suppository Using Witepsol H-15

Witepsol 중공좌제로부터의 염산프로프라놀롤 및 인도메타신의 방출제어

In oder to develop the controlled release of drugs from the suppositories, in vitro drug release and in vivo absorption in rabbits were investigated. Various suppo sitory forms with hollow cavities, into which drugs in the form of fine powder or solid dispersion system(SDS) could be placed, were utilized. The oleaginous Witepsol H-15 (WH-15) as a base, and indomethacin (IDM) of a very slightly soluble drug and propranolol-HCL (PPH) of a very soluble drug were employed as model drugs. The in vitro drug release showed that the cumulative release amount of PPH from PPH-(methylcellulose) MC-SDS and PPH-(ethylcellulose) EC-SDS hollow type suppositories reached 40% and 12% in 6 hrs,respectively. On the other hand, the drug release for a conventional suppository was 80% in 6 hrs. For the IDM suppositories,the cumulative drug release from IDM-(polyvinylpyrrolidone) PVP-SDS hollow type suppositories reached 99% in 24 hrs, whereas that from a conventional suppository reached 85%. An in vivo experiment with rabbits showed that IDM-PVP-SDS hollow type suppository delayed the absorption of IDM, significantly. The $t_{max},\;C_{max}\;and\;AUC_{0{\to}8}$ of IDM-PVP-SDS suppository were 60 min, 12.12${\mu}g$/ml and 2657${\mu}g$/ml/min, respectively. The $t_{max},\;C_{max}\;and\;AUC_{0{\to}8}$ of controlled group were 20 min, 15.49${\mu}g$/ml and 2190${\mu}g$/ml/min, respectively.