Preparation of prostaglandin E1-hydroxypropyl-beta-cyclodextrin complex and its nasal delivery in rats.

The potential use of hydroxypropyl-beta-cyclodextrin (HP-betaCD) in the solubilization and stabilization of prostaglandin E(1) (PGE(1)) was investigated. The solubility and chemical stability of PGE(1) were significantly improved upon complexation with HP-betaCD. The nasal delivery of PGE(1) from the complex formulation was also studied in Wistar rats and compared with intravenous administration. PGE(1) complex after nasal administration caused a rapid decrease of blood pressure and exhibited an obvious dose-efficacy relationship, showing results nearly similar to those obtained for intravenous route. The time to reach the peak effect (T(max)) was approximately 3-4 min. Except T(max), other pharmacodynamic parameter values such as the maximal percent of blood pressure decrease (E(max), %), the lasting time of effect (T(d)), and the area under the curve (AUC, blood pressure decrease % min) were increased with increasing the administered doses. The E(max), T(d), and in particular AUC values between doses were significantly different (P < 0.01), but T(max) between doses were not significantly different (P < 0.05). The AUC values per unit dose of PGE(1) for nasal administration, however, were smaller than those for intravenous route, probably due to the incomplete absorption of nasally administered PGE(1). Besides, the in vitro effect of the PGE(1) complex on nasal mucociliary movement was also investigated with a toad palate model. The PGE(1) complex formulation exerted only minor effect on nasal mucociliary movement. These results indicate that the PGE(1)-HP-betaCD complex formulation for nasal delivery is a very promising preparation with advantages such as rapid and effective absorption, good chemical stability, ease of administration, and minor nasal ciliotoxicity.