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 ...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 formulatedwith HP-β-CD. Methods The effect of HP-β-CD on the solubility of PGE_1 was studied by phasesolubility method. The formation of inclusion complexes of PGE_1 with HP-β-CD in the aqueoussolution was confirmed by UV spectra, circular dichroism spectroscopy, and that in the solid stateby IR spectra and X-ray diffractome-try. An solid inclusion complex of PGE_1 with HP-β-CD wasprepared by lyophilization. The dissolution rate and stability of the inclusion complex weredetermined and compared with those of PGE_1 alone. Meanwhile, the stability of PGE_1 aqueoussolutions in the presence of HP-β-CD was studied under different pH conditions. Results Thesolubility of PGE_1 increased linearly with increasing HP-β-CD concentration in various pH bufferedsolutions, showing typical A_L-type phase solubility diagrams. The stability and dissolution rateof the solid inclusion complex of PGE_1 were significantly increased, compared with those of purePGE_1 . The stability of PGE_1 in HP-β-CD solutions was also obviously improved under acidic andbasic conditions, but the stabilizing effect was absent under neutral conditions. Conclusions Thesolubility,dissolution rate and chemical stability of PGE_1 are markedly improved by complexationwith HP-β-CD: It is quite possible to prepare a stable PGE_1 inclusion complex-containing soliddosage forms, but almost impossible to obtain a stable aqueous preparation of PGE_1 formulated withHP-β-CD.展开更多
文摘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 formulatedwith HP-β-CD. Methods The effect of HP-β-CD on the solubility of PGE_1 was studied by phasesolubility method. The formation of inclusion complexes of PGE_1 with HP-β-CD in the aqueoussolution was confirmed by UV spectra, circular dichroism spectroscopy, and that in the solid stateby IR spectra and X-ray diffractome-try. An solid inclusion complex of PGE_1 with HP-β-CD wasprepared by lyophilization. The dissolution rate and stability of the inclusion complex weredetermined and compared with those of PGE_1 alone. Meanwhile, the stability of PGE_1 aqueoussolutions in the presence of HP-β-CD was studied under different pH conditions. Results Thesolubility of PGE_1 increased linearly with increasing HP-β-CD concentration in various pH bufferedsolutions, showing typical A_L-type phase solubility diagrams. The stability and dissolution rateof the solid inclusion complex of PGE_1 were significantly increased, compared with those of purePGE_1 . The stability of PGE_1 in HP-β-CD solutions was also obviously improved under acidic andbasic conditions, but the stabilizing effect was absent under neutral conditions. Conclusions Thesolubility,dissolution rate and chemical stability of PGE_1 are markedly improved by complexationwith HP-β-CD: It is quite possible to prepare a stable PGE_1 inclusion complex-containing soliddosage forms, but almost impossible to obtain a stable aqueous preparation of PGE_1 formulated withHP-β-CD.
