• 약학회지
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• 제49권4호
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• pp.260-267
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• 2005

[ $PGE_1$ ] is an endogenous substance of potent vasodialator as well as inhibitor of platelet aggregation. It has been used therapeutically in peripheral arterial occlusive disease and impotence. Intracavernous injection of $PGE_1$ for erectile dysfunction has been established for several years as a treatment option for erectile dysfunction of diverse etiologies, but this mode of administration is limited by penile discomfort, pain at the injection site, inconvenience and noncompliance. As the matter of worse, the $\beta-hydroxy$ moiety of $PGE_1$ is extremely susceptible to dehydration in solution to give inactive $PGA_1$ and $PGB_1$. For the improvement of stability, rapid absorption at action site and the convenience of application, $PGE_1$ was formulated as urethral suppositories of three types of formulations, such as PEG, witepsol, and the mixture of PEG and witepsol. The stability test of $PGE_1$ and the release test in urinary suppositories were performed. Futhermore, the effect of enhancers and vehicle composition on the penetration of $PGE_1$ through excised rat skin was evaluated by permeability coefficient and enhancement ratio.

• Journal of Pharmaceutical Investigation
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• 제30권3호
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• pp.173-178
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• 2000

The purpose of this work is to develop a transurethral suppository containing prostaglandin $E_1\;(PGE_1)$, which stabilizes the drug, gives no irritation to physiological body and enhances the erectile response of $PGE_1.\;PGE_1$ transurethral suppositories were prepared with various amounts of compositions such as saturated polyglycolysed glyceride $(Suppocire^{\circledR}\;AP,\;SAP)$, polyoxyethylene hydrogenated castor oil (HCO-50) and ethanol. The melting points, viscosities and $PGE_1$ release of the suppositories were investigated. Ocular irritation test was carried out after application of $PGE_1$ suppository to rabbit's eye. The intracavernous pressure (ICP), penile length and duration of erectile response were determined after transurethral administration of $PGE_1$ suppository and compared with those after intracavernosal injection of $PGE_1$ solution to cats. HCO-50 hardly affected the melting points and viscosities of $PGE_1$ suppositories. Additionally, $PGE_1$ transurethral suppositories, whose melting point ranges was $34-35^{\circ}C$, was speedily melted in physiological body. HCO-50 significantly decreased the dissolution rates of $PGE_1$ from the suppositories. Dissolution mechanism analysis showed the release of $PGE_1$ was proportional to the square root of time, indicating that $PGE_1$ might be released from the suppositories by Fickian diffusion. The release rate of $PGE_1$ from $PGE_1$ suppository [PGE1/SAP/HCO-50/ethanol (1/94.5/2.5/2%)] was about 80% within 2 h. This $PGE_1$ suppository gave no significant irritation to the ocular tissue, expecting that it gave no irritation to the urethral tissue less sensive than ocular tissue. Furthermore, $PGE_1$ in this suppository was stable at $4^{\circ}C$ for 2 years. This suppository increased the ICP and penile erection similar to those of injectable $PGE_1$ solution. However, it gave 2.5-fold increased duration of erectile response than injectable $PGE_1$ solution. Our results suggested that it gave more effective erectile response than injectable $PGE_1$ solution in cats. It is concluded that this $PGE_1$ suppository with good safety, excellent stability and enhanced erectile response, could be a more effective and convenient transurethal delivery system of $PGE_1$.