• Journal of Pharmaceutical Investigation
• /
• v.36 no.4
• /
• pp.223-229
• /
• 2006

[ $PGE_1$ ]-ethyl ester intraurethral solutions were prepared in ethanol/propylene glycol mixture with penetration enhancer and viscosity-enhancing agent. The stability of $PGE_1$-ethyl ester in intraurethral solution was investigated at various temperature. Simultaneous determination of $PGE_1$-ethyl ester and $PGE_1$ was performed using a validated HPLC technique. In pentobarbital anesthetized cats, increase in intracavernous pressure(ICP), increase in penile length and duration of erectile response were determined after intraurethral application of $PGE_1$-ethyl ester solutions. $PGE_1$-ethyl ester solutions, when instilled into the eyes of rabbits, produces no noticeable irritation, or slight transient conjunctival irritation. From these results, ocular irritation of this solutions was judged as practically non-irritating. The stability study indicates that the therapeutically effective content in solution is well maintained for 46 weeks or longer when they are stored at $4^{\circ}C$. After intraurethral application of $PGE_1$-ethyl ester, ICP was increased and penile erection was induced. $PGE_1$-ethyl ester intraurethral solutions for erectile dysfunction could be developed and evaluated by employing feline erection model.

• Proceedings of the PSK Conference
• /
• 2001.04a
• /
• pp.236.2-237
• /
• 2001

• Journal of Pharmaceutical Investigation
• /
• v.37 no.5
• /
• pp.291-295
• /
• 2007

Prostaglandin $E_1\;(PGE_1)$ was formulated as two self-microemulsifying drug delivery systems (SMEDDS) composed of Cremophor $EL^{(R)}$ or Cremophor $ELP^{(R)}$ as a surfactant, ethanol as a cosurfactant and Labrafac $CC^{(R)}$ as an oil to develop liquid preparation for the treatment of erectile dysfunction. In pseudo-ternary phase diagram, viscous gel area and microemulsion area were defined. In the measurement of viscosity, the viscosity of two formulations increased gradually upon the addition of water and it decreased from the water contents over 40%. With excessive water, the present systems formed a microemulsion spontaneously. From these results, rte could expect that the present liquid $PGE_1$ SMEDDS formulations might stay within the urethra in the viscous state when contacting the moisture of the urethra and can be easily eliminated by urination. In long-term stability study, we could select one formulation more stable at the shelf storage condition of $4^{\circ}C$.

• Journal of Pharmaceutical Investigation
• /
• v.34 no.2
• /
• pp.107-114
• /
• 2004

External lyogels containing prostaglandin $E_1$ ethyl ester $(PGE_1-EE)$, a prodrug of prostaglandin $E_1\;(PGE_1)$ as a therapeutic agent for erectile dysfunction, were formulated to overcome the aqueous instability and enhance the percutaneous absorption. Lyogels of $PGE_1-EE$ were prepared with ethanol (EtOH)/proplyene glycol (PG) cosolvent system as a vehicle, cineol as an enhancer, and hydroxypropylcellusose as a gelling agent. In vitro percutaneous absorption studies were performed to determine the rate of $PGE_1$ absorption through rat or hairless mouse skin. The permeability of $PGE_1-EE$ lyogel with enhancer was 16-fold greater than that of lyogel without enhancer. Cosolvent produced 9-fold increase in percutaneous absorption. Pharmacodynamic effects of lyogels were evaluated in mature male cats in terms of intracavernosal pressure (ICP). Lyogels containing 0.1 % of $PGE_1-EE$ showed higher ICP compared to intraurethral preparation of $PGE_1$ (1 %) and enhancer-free control lyogel. The shelf-life $(t_{10%})$ of lyogel at refrigerated condition $(4^{\circ}C)$ was calculated as 928 days, which is 4.2 times longer than that of control hydrogel. As a result, $PGE_1-EE$ was formulated successfully to a lyogel system with a selective enhancer and cosolvent system for the topical delivery of $PGE_1$.