Study On The Synthesis Of Sulfobutyl Ether β-cyclodextrin And Their Inclusion Compound With Azithromycin

Now, the solubilization of non-aqueous drugs gives rise to extensive attention. The solubility of drug not only directly influences the dissolution of drugs in vivo and bioavailability, but also seriously influences the clinical curative effect of concentration dependent drugs. Recently, it was found that CD can accommodate different kinds of non-aqueous drugs in the cavity, forming host-guest inclusion complexes, therefore, the dissolubility of non-aqueous drugs can be improved remarkably, and also a series of problems of non-aqueous drugs preparation can be solved. However, its anomalous low aqueous solubility, renal toxicity and hemoylsis are serious barrieres in its wider utilization. In this work, a kind of water-solubleβ-CD derivative (represented SBE-β-CD) has been synthesized. The inclusion mechanism of CD and drugs was studied by preparation of the AM/CD inclusion complexes. The content and result of this study as follows:â‘ Withβ-CD and 1,4-butane sultone as the main reagents , three different degrees of substitution of SBE-β-CD were synthesized. The specific substitution position of hydroxyl inβ-CD was selected and the DS of product was controlled by choosing a suitable reaction conditions. The solution was then filtered with an ultrafiltration cell or glucan gel filtration chromatography to wash out the small moleuar inorganic salts and to concentrate the solution. Then the retentate solution was freeze-dried to give white powers. IR, 1H-NMR and EIS-MS were used in the characterization, and indicates that bulky substituents prefer to react with the primary hydroxyl groups on C-6, also the DS of product has been exactly controlled.â‘¡The inclusion complexes of AM/β-CD, AM/M-β-CD and AM/SBE7-β-CD were prepared by using ultrasonic method. Inclusion rate and yield of the three inclusion complexes have been valued. It showed that the inclusion result was as follows: SBE₇-β-CD>>M-β-CD>β-CD. In the present work, inclusion complex of macromolecule drug AM was successfully prepared with chemical modified CD.â‘¢The phase-solubilization data of AM toβ-CD,M-β-CD and SBE7-β-CD were determined under the temperature of 25℃, 37℃and 50℃. The inclusion mechanism has been investigated by the analysis of the thermodynamic parameter of inclusion complexes. The result indicated that the solubilization of AM in SBE₇-β-CD was the best, and a liquid formulation of AM could be prepared by forming inclusion complexes. The inclusion mechanism between CD and AM was determined by the equilibrium constant and it is showed as follows: SBE₇-β-CD>>M-β-CD>β-CD. The determination factor in the preparation of inclusion complexe is hydrogen bond and van der Waals force. In the sight of ?G ,the folumation of inclusion complexes is a spontaneous and exothermic reaction. In addition, the reaction would be easier at lower temperature.