| Non-steroidal anti-inflammatory drugs (NSAIDs) are a class of clinical drugswhich have potent antipyretic, analgesic and anti-inflammatory effects. Along with thedevelopment of science and technology, more and more NSAIDs with better clinicaleffects and efficacy have appeared. Nimesulide(Nim) is a new, highly selectivenon-steroidalanti-inflammatory drug, which shows strong inhibition for theinflammatory cox-2activity, but no effect for the normal levels of cox-1, the exclusiveeffect can not only greatly reduce the damage of NSAIDs on liver and kidney function,but also greatly improve its anti-inflammatory effects, but the poor solubility of Nim inwater causes extremely low biological utilization rate, so choosing the appropriatemethod to improve its solubility in water is a serious problem must to be solved.Supramolecular chemistry is a new subject, more and more people focus on it inrecent years. It began in the crown ether and cryptand research, rapid development isobtained due to molecular self-assembly.There are a number of intermolecular forces inmolecules, supramolecular system is composed of multiple molecules throughintermolecular forces. It is a targeting aggregate. Cyclodextrin (CD) is one of the mostimportant subjects in the supramolecular chemistry, which has special properties. Dueto the hydrophobic cavity, it can accommodate water-insoluble molecules, while thehydrophilic outer layer can easily dissolve in water, so the water solubility ofhydrophobic drugs has improved, while the non-polar molecular force also uniform andstable the system. However, natural cyclodextrins have certain side effects on the body,in recent years a growing number of cyclodextrin derivatives have been synthesized, thelab made the natural β-CD into1,4-butane sultone,thus forming a class of low toxicity,highly water-soluble derivatives of β-CD: Sulfobutyl ether-β-cyclodextrin (SBE–β-CD).Modification of sulfobutyl side chain changes the molecule charge of β-CD, alsoimproves the inclusion effect of β-CD to neutral and positive drugs, at the same time,hemolytic, renal toxicity and irritation greatly reduced. The inclusion of Nim andSulfobutyl ether-β-cyclodextrin can not only improve the bioavailability, but alsogreatly reduce the side effects, which is a research direction of actual value.The research and results in this paper are as follows：①First of all, with UV spectrophotometry and HPLC method, contentdetermination of Nim was established, by the requirements of pharmacopoeia2010, the results show that the appearance, melting point, absorbance, PH, related substances, dryweightlessness of Nim can conform to the requirements well. Additionally,UVspectrophotometry and HPLC method were adopted to construct the Nim standard curve,the recycling experiment, stability experiment and precision show that the method is ofhigh precision, stable and reliable.②Equimolar concentration method and phase solubility method were used todetermine the inclusion mole ratio of Nim and β-CD, M-β-CD, HP-β-CD andSBE7-β-CD, four inclusion compounds were prepared, through quantity, yield andevaluation of four kinds of cyclodextrin inclusion, the results show that：SBE7-β-CD>HP-β-CD> M-β-CD>β-CD, so choose SBE7-β-CD to be the optimal inclusion assupplementary material.③Freeze-drying was choosed for the preparation of SBE7-β-CD with Nimsupramolecular inclusion compound, using the single factor experiment method ofinclusion temperature, the closure time and PH value on package filtering, optimize theinclusion process, the data showed that SBE7-β-CD with Nim at80℃,60min, reachedthe maximum under the condition of PH6.82. In addition, the preparation of inclusioncompound with ultraviolet spectrometry, infrared spectrometry, mass spectrometry,microscope observation method, and the molecular simulation method of clathratestructure identification and characterization, the results show that the SBE7-β-CD withNim supramolecular inclusion compound has been formed.④Respectively, the phase data of Nim and SBE7-β-CD in35℃and55℃,75℃,study of inclusion in the process of thermodynamic parameters changes, the Nim andSBE7-β-CD for the exothermic process (ΔH <0). At35℃and55℃,75℃, the gibbsfree energy of ΔG is negative, the inclusion process can occur spontaneously in thedifferent temperatures. ΔS>0, the inclusion of guest molecules with stability. Inaddition, as temperatures rise, SBE7-β-CD to Nim solubilization, inclusion compound ofapparent stability constants K decreases, and the formation of the inclusion compoundwas a enthalpy drive process.⑤Emulsification method was used for the preparation of Nim with SBE7-β-CDinto ointments, and suitable for clinical use and cream preparation for the identificationand evaluation, the results show that the ointments was soft paste evenly, stability. |
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