Preparation and Evaluation of Liquid Suppository Containing Prostaglandin $E_1-loaded$ Microemulsion

프로스타글란딘 $E_1$ 마이크로에멀젼이 함유된 액상좌제의 제조 및 평가

The purpose of this study is to develop a transurethral liquid suppository containing prostaglandin $E_1\;(PGE_1)-loaded$ microemulsion, which undergoes a phase transition to gels at body temperature. The effects of oils, ethanol as solvent and HCl as pH-controlling agent on the physicochemical properties of liquid suppositories composed of poloxamer P 407, P 188 and carbopol was investigated. The stability of $PGE_1$ and release of $PGE_1$ from liquid suppository were evaluated. Oils such as Neobee and soybean oil significantly decreased the gelation temperature but increased the gel strength of liquid suppository due to their strongly binding with the components of liquid suppository base. However, ethanol slightly did the opposite. The pH of liquid suppositories hardly affected the gelation temperature and gel strength due to addition of very small HCl (0.005-0.01%). A liquid suppository [$PGE_1/P$ 407/P 188/carbopol/Neobee/ethanol/HCl (0.2/14/14/0.4/7/2/0.005%)], which had the gelation temperature $(34.2{\pm}0.6^{\circ}C)$ and gel strength $(31.35{\pm}4.37\;sec)$ suitable for liquid suppository system, was easily administered and not leak out from the body. About 60% of $PGE_1$ was released out within 2 h from this formulation. It was shown that the release of $PGE_1$ was proportional to the square root of time, indicating that $PGE_1$ might be released from the suppository by Fickian diffusion. It was stable at $4^{\circ}C$ for at least 2 months. The results suggest that transurethral liquid suppository containing prostaglandin $E_1-loaded$ microemulsion is thought to be a convenient, safe and effective dosage form for $PGE_1$. However, it should be further developed as a more convenient and stable dosage form for $PGE_1$.