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提高阿苯达唑在泊洛沙姆 188 固体分散体中的溶出速率。

Improved albendazole dissolution rate in pluronic 188 solid dispersions.

机构信息

Departamento de Farmacia, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Argentina, CONICET.

出版信息

AAPS PharmSciTech. 2010 Dec;11(4):1518-25. doi: 10.1208/s12249-010-9517-6. Epub 2010 Oct 14.

Abstract

Solids dispersions (SDs) have been proposed as an alternative to improve the dissolution rate of low solubility drugs. SDs containing albendazole (ABZ; 5, 10, 25, and 50% w/w) and Pluronic 188 (P 188) as hydrophilic carrier were formulated. The obtained SDs were assessed in comparison to physical mixtures (PMs). Drug-polymer interactions in solid state were investigated using Fourier-transform infrared spectroscopy, scanning electron microscopy, and X-ray diffraction analysis. No chemical interaction was found between ABZ and poloxamer. The dissolution profiles indicated that ABZ incorporated in SDs and PMs was rapidly released, reaching rapidly the steady state. Increased dissolution rates are usually observed at the highest polymer proportions. However, an opposite effect for SDs as well as for PMs was observed in the assays described here. The systems with the lowest P 188 percentages (SD4, SD3; PM4, PM3) tended to be more effective in increasing the ABZ dissolution rate. Such a result can be attributed to the fact that concentrated aqueous solutions of Poloxamer may form thermo-reversible gels. The physical-mechanical properties indicated that SDs possess improved flow and compacting properties compared to PMs. Thus, ABZ SDs would be more convenient for solid dosage form design and manufacture.

摘要

固体分散体(SDs)已被提议作为一种替代方法,以提高低溶解度药物的溶解速率。本文制备了含有阿苯达唑(ABZ;5、10、25 和 50%w/w)和泊洛沙姆 188(P 188)作为亲水性载体的 SDs,并将其与物理混合物(PMs)进行了比较。使用傅里叶变换红外光谱、扫描电子显微镜和 X 射线衍射分析研究了固体状态下药物-聚合物的相互作用。ABZ 与聚氧乙烯醚之间未发现化学相互作用。溶解曲线表明,SDs 和 PMs 中包埋的 ABZ 迅速释放,迅速达到稳定状态。通常在聚合物比例最高时观察到溶解速率增加。然而,在本文描述的测定中,SDs 和 PMs 均观察到相反的效果。P 188 百分比最低的系统(SD4、SD3;PM4、PM3)往往更有效地提高 ABZ 的溶解速率。这一结果可归因于这样一个事实,即聚氧乙烯醚的浓水溶液可能形成热可逆凝胶。物理力学性质表明,SDs 与 PMs 相比,具有更好的流动和压实性能。因此,ABZ-SDs 将更便于设计和制造固体制剂。

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