PDF(Pubmed)
Abstract：
Olmesartan medoxomil (OLM) is a selective angiotensin II receptor antagonist used in the treatment of hypertension. Its therapeutic potential is limited by its poor water solubility, leading to poor bioavailability. Encapsulation of the drug substance by two methylated cyclodextrins, namely randomly methylated β-cyclodextrin (RM-β-CD) and heptakis(2,3,6-tri-O-methyl)-β-cyclodextrin (TM-β-CD), was carried out to overcome the limitation related to OLM solubility, which, in turn, is expected to result in an improved biopharmaceutical profile. Supramolecular entities were evaluated by means of thermoanalytical techniques (TG-thermogravimetry; DTG-derivative thermogravimetry), spectroscopic methods including powder X-ray diffractometry (PXRD), universal-attenuated total reflectance Fourier-transform infrared (UATR-FTIR) and UV spectroscopy, saturation solubility studies, and by a theoretical approach using molecular modeling. The phase solubility method reveals an AL-type diagram for both inclusion complexes, indicating a stoichiometry ratio of 1:1. The values of the apparent stability constant indicate the higher stability of the host-guest system OLM/RM-β-CD. The physicochemical properties of the binary systems are different from those of the parent compounds, emphasizing the formation of inclusion complexes between the drug and CDs when the kneading method was used. The molecular encapsulation of OLM in RM-β-CD led to an increase in drug solubility, thus the supramolecular adduct can be the subject of further research to design a new pharmaceutical formulation containing OLM, with improved bioavailability.
摘要：
奥美沙坦酯（OLM）是一种用于治疗高血压的选择性血管紧张素II受体拮抗剂。它的治疗潜力受到其水溶性差的限制，导致生物利用度差。用两种甲基化环糊精封装药物，即随机甲基化β-环糊精（RM-β-CD）和七（2,3,6-三-O-甲基）-β-环糊精（TM-β-CD），进行是为了克服与OLM溶解度相关的限制，which,反过来,预计将导致改进的生物制药概况。通过热分析技术（TG-热重法；DTG-衍生热重法）评估了超分子实体，光谱学方法包括粉末X射线衍射(PXRD),通用衰减全反射傅里叶变换红外(UATR-FTIR)和紫外光谱,饱和溶解度研究，并通过使用分子建模的理论方法。相溶解度方法揭示了两种包合物的AL型图，表示化学计量比为1:1。表观稳定常数的值表明主-客体系统OLM/RM-β-CD的稳定性较高。二元体系的物理化学性质不同于母体化合物的物理化学性质,强调使用捏合方法时药物和CD之间包合物的形成。OLM在RM-β-CD中的分子包封导致药物溶解度增加，因此，超分子加合物可以作为进一步研究的主题，以设计含有OLM的新药物制剂，提高生物利用度。
