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

The potential use of hydroxypropyl-β-cyclodextrin (HP-βCD) in the solubilization and stabilization of prostaglandin E1 (PGE1) was investigated. The solubility and chemical stability of PGE1 were significantly improved upon complexation with HP-βCD. The nasal delivery of PGE1 from the complex formulation was also studied in Wistar rats and compared with intravenous administration. PGE1 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 (Tmax) was approximately 3-4 min. Except Tmax, other pharmacodynamic parameter values such as the maximal percent of blood pressure decrease (Emax, %), the lasting time of effect (Td), and the area under the curve (AUC, blood pressure decrease % min) were increased with increasing the administered doses. The Emax, Td, and in particular AUC values between doses were significantly different (P < 0.01), but Tmax between doses were not significantly different (P < 0.05). The AUC values per unit dose of PGE1 for nasal administration, however, were smaller than those for intravenous route, probably due to the incomplete absorption of nasally administered PGE1. Besides, the in vitro effect of the PGE1 complex on nasal mucociliary movement was also investigated with a toad palate model. The PGE1 complex formulation exerted only minor effect on nasal mucociliary movement. These results indicate that the PGE1-HP-βCD 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.