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Studies On The Preparation Of Inclution Complexes Of Osthol-β-Cycclodextrin And Absorption Through Nasal Membrane And Skin

Posted on:2008-02-20Degree:MasterType:Thesis
Country:ChinaCandidate:J Y SongFull Text:PDF
GTID:2144360215980741Subject:Pharmaceutical Engineering
Abstract/Summary:PDF Full Text Request
The phase solubility curves of the OST was obtained by determining the solubility of OST in different concentrations ofβ-CD and its derivatives (HP-β-CD or M-β-CD ). The result of the experiment indicated that the phase solubility curves of the OST in three different cyclodextrins were A styles and the inclusion ratio of OST versus cyclodextrins was 1:1.The binding constants were 296.0 L·mol-1,441.8 L·mol-1 and 397.9 L·mol-1 , respectively. The enhancing effect of OST solubility with HP-β-CD and M-β-CD was better than that ofβ-CD.The osthol-hydroxypropyl-β-cyclodextrin inclusion complex was prepared by solution-stirring method. The factors affecting inclusion compound were studied with orthogonal test. The optimized condition for the formation of osthol-hydroxypropyl-β-cyclodextrin inclusion compound was: stirring for 12hours at 40℃in 55% ethanol. The solubility of the inclusion complex and the dissolution rate were determined by UV. The inclusion compound of osthol-HP-β-CD was confirmed by differential scanning calorimetry (DSC) method. The solubility of the osthol was greatly increased from 3.5 mg·L-1 to 30 mg·L-1 when the drug was included by hydroxypropyl-β-cyclodextrin, and the drug dissolution rate in vitro was increased by 4 times in 2 hours.The experiment of nasal membrane absorption showed that drug had a good permeation through nasal membrane, but the drug would occur degradation in the grume of the nasal membrane and the silicon rubber tube would have adsorption for the drug. The experiment showed that the drug was not stable in the grume of the nasal membrane, and the drug would be adsorbed mostly in different solution (pH3.5,4.5,5.5,6.5,7.5,0.9% sodium chloride solution)in silicon rubber tube. In 2 hours, the adsorption ratios reached 97%( pH3.5) and 69% (pH7.5) , respectively.Compared with the free drug, the inclusion complex had a better permeation through skin. The oleic acid would enhance the permeation of the drug and the optimal concentration was 8%.
Keywords/Search Tags:osthol, hydroxypropyl-β-cyclodextrin, inclusion complexes, absorption through nasal membrane, absorption through skin
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