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甲基-β-环糊精与奥氮平包合物作为治疗精神分裂症的潜在药物传递系统。

Inclusion complex of methyl-β-cyclodextrin and olanzapine as potential drug delivery system for schizophrenia.

机构信息

Core of Medicines and Corelated Quality Control - NCQMC, Department of Pharmaceutical Sciences - Federal University of Pernambuco, Arthur de Sá, s/n. 50740-521 Recife, PE, Brazil.

Laboratory of Medicines Technology - LTM, Department of Pharmaceutical Sciences - Federal University of Pernambuco, Arthur de Sá, s/n. 50740-521 Recife, PE, Brazil.

出版信息

Carbohydr Polym. 2012 Aug 1;89(4):1095-100. doi: 10.1016/j.carbpol.2012.03.072. Epub 2012 Apr 1.

Abstract

Olanzapine (OLP), the most important atypical antipsychotic drug of the new generation, a high cost drug, has low aqueous solubility, affecting its dissolution and absorption. Its complexation with modified cyclodextrins (CDs) is designed to achieve novel vectorization systems with higher solubility, consequently higher bioavailability. From the CD selection, among β-CD, methyl-β-CD (MβCD) and hydroxypropyl-β-CD, it was obtained a phase solubility diagram suggesting a 1:1 (mol:mol) OLP-CD stoichiometry and complexation constants of 966.9, 149.4 and 91.1 L/mol, respectively. The MβCD was selected for the inclusion complexes (IC) attainment, a physical mixture (PM) and a rotatory evaporator product (ROE). The analysis showed differences in the structure, morphology and performance of OLP, MβCD, PM and ROE, revealing the occurrence of interactions between drug and CD. The ROE presented the higher dissolution efficiency and stability. The results suggest that the IC was formation, being a technological resource efficient and profitable for drug delivery.

摘要

奥氮平(OLP)是新一代最重要的非典型抗精神病药物,一种高成本药物,其水溶性低,影响其溶解和吸收。它与改性环糊精(CDs)的络合旨在实现具有更高溶解度的新型载体系统,从而提高生物利用度。从 CD 选择中,β-CD、甲基-β-CD(MβCD)和羟丙基-β-CD,得到了一个相溶解度图,表明 OLP-CD 的摩尔比为 1:1(摩尔:摩尔),络合常数分别为 966.9、149.4 和 91.1 L/mol。选择 MβCD 以获得包含配合物(IC)、物理混合物(PM)和旋转蒸发器产物(ROE)。分析表明 OLP、MβCD、PM 和 ROE 的结构、形态和性能存在差异,表明药物与 CD 之间存在相互作用。ROE 表现出更高的溶解效率和稳定性。结果表明,IC 的形成是一种高效且有利可图的药物传递技术资源。

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