Effect of Complexation with Hydroxylpropyl-β-Cyclodextrin on Solubility, Dissolution Rate and Chemical Stability of Prostaglandin E_1

摘要

Aim To study the effect of complexation with hydroxylpropyl-β-cyclodextrin (HP-β-CD) on the solubility, dissolution rate and chemical stability of prostaglandin E_1 (PGE_1) , thereby providing a basis for preparing a stable solid or aqueous preparation of PGE_1 formulated with HP-β-CD. Methods The effect of HP-β-CD on the solubility of PGE_1 was studied by phase solubility method. The formation of inclusion complexes of PGE_1 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 diffractome-try. An solid inclusion complex of PGE_1 with HP-β-CD was prepared by lyophilization. The dissolution rate and stability of the inclusion complex were determined and compared with those of PGE_1 alone. Meanwhile, the stability of PGE_1 aqueous solutions in the presence of HP-β-CD was studied under different pH conditions. Results The solubility of PGE_1 increased linearly with increasing HP-β-CD concentration in various pH buffered solutions, showing typical A_L-type phase solubility diagrams. The stability and dissolution rate of the solid inclusion complex of PGE_1 were significantly increased, compared with those of pure PGE_1 . The stability of PGE_1 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 PGE_1 are markedly improved by complexation with HP-β-CD: It is quite possible to prepare a stable PGE_1 inclusion complex-containing solid dosage forms, but almost impossible to obtain a stable aqueous preparation of PGE_1 formulated with HP-β-CD.