The Study On Inclusion Thermodynamics Of Different Cyclodextrin Derivatives And Three Drugs

The solubility is related to drug dissolution and in vivo bioavailability, and it has direct impact on the clinical outcome. In recent years, it was noted that a package cyclodextrin derivatives cooperation on drug use, to the formation of drugs and drug - cyclodextrin inclusion complex derivatives to improve the physical and chemical properties of drugs in order to improve it's solubility, and reduce drug side effects as well as solve series problems of insoluble drugs. The subject used three different molecular weight nitrogen-containing drugs (sulfamonomethoxine, norfloxacin, cilostazol) as the research object, the first effects of different temperatures commonly used three different molecular weight nitrogen-containing drugs and paste fine co-operations with the nature of the derivatives of package and prepare the corresponding inclusion complexes were determined and their evaluation; determination of the three main ingredients in the package with five dextrin derivatives, the equilibrium constant, determined the molar ratio of host and guest molecular inclusion, compared the main inclusion difference with various drugs and different cyclodextrin derivatives; the study of the thermodynamic changes in the process of inclusion and investigates the mechanism of inclusion from the thermodynamics, for future researching to explore new ideas.The content and results of this study are as follows:①Method of continue change of molar concentration has been used to ensure the best inclusion molar ratio of the three drugs (sulfamonomethoxine, norfloxacin, cilostazol) and five cyclodextrin derivatives. through the inclusion of the yield, drug content, encapsulation efficiency and evaluation of dissolution four main drugs of different molecular weight cyclodextrin derivatives and inclusion of different properties, and to yield, encapsulation efficiency and dissolution rate as the main evaluation criteria. The results show that the recovery rate, from the perspective of the main drug, the inclusion of cilostazol was the highest yield of product; from the perspective of the cyclodextrin derivatives, the highest recovery rate is SPE7-β-CD and SBE7-β-CD inclusion product. Encapsulation rate, from the perspective of the cyclodextrin derivatives, the highest encapsulation efficiency is SPE7-β-CD and SBE7-β-CD inclusion of the product; from the perspective of the main drug, cilostazol package complexes the highest encapsulation efficiency. SPE7-β-CD and SBE7-β-CD through the modification, and increased water-soluble, hydrophilic best, but also expanded the cavity spatial scale, more suitable for inclusion materials; cilostazol relatively large molecular weight and the ring dextrin derivatives inclusion process more matches, as well as its unique spatial structure are able to paste into the ring hollow cavity derivatives, can be a better inclusion.②The solubility data of sulfamonomethoxine, norfloxacin, cilostazol andβ-CD, HP-β-CD, M-β-CD, SPE7-β-CD, SBE7-β-CD were determined at 25℃, 37℃and 45℃, comparative analysis of different CD derivative sulfamosno-methoxine, norfloxacin, solubilization of cilostazol effect, and the linearly regression to calculate their inclusion equilibrium constants, validation of drug cyclodextrin derivative guest molecules and the best molar ratio of inclusion.③Investigating by the properties of inclosure, it has studied the parameters(K,ΔG,ΔH,ΔS) of the thermodynamic changes. The results showed that: different drugs with different CD derivatives, respectively, the temperature was 25℃, 37℃, 45℃of inclusion when used, the host and guest molecules are 1:1 molar ratio of inclusion, the main drug for different purposes, norfloxacin and cyclodextrin derivatives in the process of inclusion equilibrium constant maximum, and in the choice of three common nitrogen-containing drugs, norfloxacin low PH value, indicating that the main drugs PH inclusion of the stability and ease of inclusion; cyclodextrin derivatives for different purposes SPE7-β-CD, SBE7-β-CD with different kinds of closing with the main inclusion equilibrium constant maximum, hydrophilic stronger, the more stabler inclusion complex formed, the easier the process of inclusion.Similarly, It's draw the relevant conclusions ofΔG,ΔH,ΔS by comparing and analysising, it indicates that the inclusion complex of the three common drugs (sulfamonomethoxine, norfloxacin, cilostazol) and five CD derivatives (β-CD, HP-β-CD, M-β-CD, SPE7-β-CD, SBE7-β-CD) not only related to the molecular weight of the object, but also concern the kinds of cyclodextrin derivatives. The inclusion process is exothermic (ΔH <0), thus increasing the temperature, the inclusion process will be towarded to the direction of dissociation, increasing theΔS; hydrophobic interaction in favour of the closuring because of it can also adding theΔS. Gibbs free energy (ΔG) all negative at 25℃, 37℃, 45℃, and that theΔG'changes of Cilostazol is the most, It can be seen that the inclusion is spontaneous at The different temperature.