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Abstract：
Risperidone (RSP) is an atypical antipsychotic drug which acts as a potent antagonist of serotonin-2 (5TH2) and dopamine-2 (D2) receptors in the brain; it is used to treat schizophrenia, behavioral and psychological symptoms of dementia and irritability associated with autism. It is a poorly water soluble benzoxazole derivative with high lipophilicity. Supramolecular adducts between drug substance and two methylated β-cyclodextrins, namely heptakis(2,6-di-O-methyl)-β-cyclodextrin (DM-β-CD) and heptakis(2,3,6-tri-O-methyl)-β-cyclodextrin (TM-β-CD) were obtained in order to enhance RSP solubility and improve its biopharmaceutical profile. The inclusion complexes were evaluated by means of thermoanalytical methods (TG-thermogravimetry/DTG-derivative thermogravimetry/HF-heat flow), powder X-ray diffractometry (PXRD), universal-attenuated total reflectance Fourier transform infrared (UATR-FTIR), UV spectroscopy and saturation solubility studies. Job\'s method was employed for the determination of the stoichiometry of the inclusion complexes, which was found to be 2:1 for both guest-host systems. Molecular modeling studies were carried out for an in-depth characterization of the interaction between drug substance and cyclodextrins (CDs). The physicochemical properties of the supramolecular systems differ from those of RSP, demonstrating the inclusion complex formation between drug and CDs. The RSP solubility was enhanced as a result of drug encapsulation in the CDs cavity, the higher increase being obtained with DM-β-CD as host; the guest-host system RSP/DM-β-CD can thus be a starting point for further research in developing new formulations containing RSP, with enhanced bioavailability.
摘要：
利培酮（RSP）是一种非典型的抗精神病药物，可作为大脑中5-羟色胺2（5TH2）和多巴胺2（D2）受体的有效拮抗剂;它用于治疗精神分裂症，与自闭症相关的痴呆和易怒的行为和心理症状。它是一种水溶性差的苯并恶唑衍生物，具有高亲油性。药物和两种甲基化β-环糊精之间的超分子加合物，获得了七（2,6-二-O-甲基）-β-环糊精（DM-β-CD）和七（2,3,6-三-O-甲基）-β-环糊精（TM-β-CD），以提高RSP的溶解度并改善其生物制药特性。通过热分析方法（TG-热重法/DTG-衍生热重法/HF-热流法）评估包合物，粉末X射线衍射（PXRD），通用衰减全反射傅里叶变换红外(UATR-FTIR),紫外光谱和饱和溶解度研究。Job\'s方法用于测定包合物的化学计量，对于两个来宾主机系统，发现均为2：1。进行了分子建模研究，以深入表征药物与环糊精（CD）之间的相互作用。超分子系统的物理化学性质不同于RSP,证明药物和CD之间的包合物形成。由于药物封装在CD腔中，RSP溶解度得到增强，以DM-β-CD为宿主可获得更高的增加；因此，客体-宿主系统RSP/DM-β-CD可以成为进一步研究开发含RSP的新配方的起点。具有增强的生物利用度。
