The Inclusion Of Beta-cyclodextrin Derivatives And Release Properties

β-cyclodextrins(CDs) are made of seven glucopyranose units linked byα(1â†'4) bonds. They have a hydrophilic outer surface and a hydrophobic inner cavity and their internal cavities could form inclusion complexes with hydrophobic guest molecules. In the pharmaceutical field, cyclodextrins are used essentially for improving drug stability and dissolution rates; cyclodextrins could also modify drug release profile from many controlled release drug delivery systems. Various CD derivatives have been developed during the past decades, which extensively expanded the applications of CDs and overcome the serious drawbacks of parent CDs such as low water solubility. In this article, we have modified theβ-CD and a reactiveβ-CD based monomer carrying vinyl carboxylic acid functional groups was synthesized via reaction ofβ-CD with maleic anhydride. MAH-β-CD shows a good solubility. The pH sensitive hydrogels based on cyclodextrins were prepared by the copolymerization of MAH-β-CD and the pH sensitive materials. Then we have studied the in vitro drug release properties of the hydrogels.The thesis consists of the following four parts:1 Preparation and properties of resveratrol/maleic anhydride-β-cyclodextrin inclusion complex. Complex of resveratrol with MAH-β-CD was obtained by using the freeze-drying method. Solid state characterization of the products was carried out using FTIR,XRD and UV-VIS technology. Phase solubility diagram with maleic anhydride-β-cyclodextrin was classified as AL type, indicating the formation of 1:1 stoichiometric inclusion complex. Stability constant from the phase solubility diagram was calculated as 2.0×103 L/mol. Its scavenging effect on·OH was studied, data showed that the inclusion phenomenon did not significatively interfere with its biological property. Stability studies in solution were performed, the photodegradation by HPLC was monitored, the isomerization rate trans to cis, decreased with the formation of inclusion complex. The dissolution studies revealed that the solubility of resveratrol in water increased about two times with the formation of inclusion complex.2 Preparation and characterization of luteolin/maleic anhydride-β-cyclodextrin inclusion complex. The purpose of this paper was to improve the solubility of luteolin by preparing the complex of luteolin with MAH-β-CD. The complex was obtained by using the freeze-drying method. Solid state characterization of the products was carried out using FTIR, XRD and UV-VIS technology. Phase solubility diagram with maleic anhydride-β-cyclodextrin was classified as AL type. Stability constant from the phase solubility diagram was calculated as 2.1×102L/mol. The dissolution studies revealed that the solubility of luteolin increased about one time with the formation of inclusion complex. Luteolin and MAH-β-CD could form the 1:1 stoichiometric inclusion complex, and the solubility of luteolin in water was improved.3 Preparation and sustained release properties of poly (β-cyclodextrin/ methacrylic acid) hydrogel. The P(MAH-β-CD/MAA) hydrogel based on cyclodextrins was prepared by the copolymerization of MAH-β-CD and MAA using a redox initiator system in aqueous solution. The composition of hydrogel was analyzed by FTIR spectra. Swelling measurements indicated that the hydrogel exhibits good pH-sensitivity. It was determined that the toxicity reaction of either group was zero grade. Resveratrol and luteolin were chosen as the model of hydrophobic drug and the mechanism for drug release from the hydrogel was deduced by Peppas' formula, the results showed that the drug release was controlled by Fickian diffusion.4 Preparation and sustained release properties of P(MAH-β-CD/AA) hydrogel. The P(MAH-β-CD/AA) hydrogel was prepared by the copolymerization of AA and MAH-β-CD using a redox initiator system in aqueous solution. The composition of hydrogel was analyzed by FTIR spectra. The swelling ratio of hydrogel indicated that the hydrogel exhibits good pH-sensitivity. It was determined that the toxicity reaction of either group was zero grade. Resveratrol and luteolin were chosen as the model of hydrophobic drug and the mechanism for drug release from the hydrogel was deduced by Peppas' formula. The results showed that the drug release was controlled by Fickian diffusion. The hydrogel material is desirable for potential applications as hydrophobic drug delivery systems.