Abstract: Aim To study the effect of complexation with hydroxylpropyl-β-cyclodextrin (HP-β-CD) on the solubility,dissolution rate and chemical stability of prostaglandin E1 (PGE1), thereby providing a basis for preparing a stable solid or aqueous preparation of PGE1 formulated with HP-β-CD. Methods The effect of HP-β-CD on the solubility of PGE1 was studied by phase solubility method. The formation of inclusion complexes of PGE1 with HP-β-CD in the aqueous solution was confirmed by UV spectra, circular dichroism spectroscopy, and that in the solid state by IR spectra and X-ray diffractometry. An solid inclusion complex of PGE1 with HP-β-CD was prepared by lyophilization. The dissolution rate and stability of the inclusion complex were determined and compared with those of PGE1 alone. Meanwhile, the stability of PGE1 aqueoussolutions in the presence of HP-β-CD was studied under different pH conditions. Results The solubility of PGE1 increased linearly with increasing HP-β-CD concentration in various pH buffered solutions, showing typical AL-type phase solubility diagrams. The stability and dissolution rate of the solid inclusion complex of PGE1 were significantly increased, compared with those of pure PGE1. The stability of PGE1 in HP-β-CD solutions was also obviously improved under acidic and basic conditions, but the stabilizing effect was absent under neutral conditions. Conclusions The solubility,dissolution rate and chemical stability of PGE1 are markedly improved by complexation with HP-β-CD. It is quite possible to prepare a stable PGE1 inclusion complex-containing solid dosage forms, but almost impossible to obtain a stable aqueous preparation of PGE1 formulated with HP-β-CD.

Key words: PGE1, PGE1, HP-β-CD, HP-β-CD, inclusion complex, inclusion complex, solubility, solubility, dissolution rate, dissolution rate, stability, stability