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通过喷雾干燥技术制备的美洛昔康 - HPβCD与聚乙烯吡咯烷酮或L - 精氨酸的三元复合物的表征

Characterization of ternary complexes of meloxicam-HPbetaCD and PVP or L-arginine prepared by the spray-drying technique.

作者信息

El-Maradny Hoda A, Mortada Sana A, Kamel Ola A, Hikal Ahmed H

机构信息

Department of Industrial Pharmacy, University of Alexandria, Alexandria, Egypt.

出版信息

Acta Pharm. 2008 Dec;58(4):455-66. doi: 10.2478/v10007-008-0029-9.

Abstract

Ternary complexes of meloxicam (ME) (a poorly water soluble anti-inflammatory drug) with hydroxypropyl-beta-cyclodextrin (HPbetaCD) and either a hydrophilic polymer, namely, polyvinyl pyrrolidone (PVP) or a basic amino acid such as L-arginine, were prepared by the spray-drying technique. The solubilizing efficiency, physical properties and dissolution behaviour of each ternary system of ME-HPbetaCD with either PVP or L-arginine were compared with those of the corresponding binary system of ME-HPbetaCD. Tablets compressed from the ternary system of ME-HPbetaCD-L-arginine were compared with plain and commercial tablets. Phase solubility experiments suggested the formation of an inclusion complex of AL type. Ternary system of ME-HPbetaCD-L-arginine exhibited a stability constant 30.3 times higher than the binary system of ME-HPbetaCD, while the ternary system of ME-HPbetaCD-PVP increased the stability constant 2.2 times only. The prepared complexes were characterized by scanning electron microscopy, differential scanning calorimetry and infra red spectroscopy. Ternary solid complexes indicated the presence of strong interactions between the components. The dissolution behaviour of ME from different ternary complexes was higher than its dissolution from the binary system. Tablets compressed from ternary complexes of ME-HPbetaCD-L-arginine highly improved drug release compared to plain and commercial tablets.

摘要

通过喷雾干燥技术制备了美洛昔康(ME,一种水溶性差的抗炎药物)与羟丙基-β-环糊精(HPβCD)以及亲水性聚合物聚乙烯吡咯烷酮(PVP)或碱性氨基酸L-精氨酸形成的三元复合物。将ME-HPβCD与PVP或L-精氨酸形成的每个三元体系的增溶效率、物理性质和溶解行为与相应的ME-HPβCD二元体系进行了比较。将由ME-HPβCD-L-精氨酸三元体系压制的片剂与普通片剂和市售片剂进行了比较。相溶解度实验表明形成了AL型包合物。ME-HPβCD-L-精氨酸三元体系的稳定常数比ME-HPβCD二元体系高30.3倍,而ME-HPβCD-PVP三元体系仅将稳定常数提高了2.2倍。通过扫描电子显微镜、差示扫描量热法和红外光谱对制备的复合物进行了表征。三元固体复合物表明各组分之间存在强相互作用。ME从不同三元复合物中的溶解行为高于其从二元体系中的溶解行为。与普通片剂和市售片剂相比,由ME-HPβCD-L-精氨酸三元复合物压制的片剂显著改善了药物释放。

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