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原料和工艺变量对快速干燥模式下喷雾干燥包封药物悬浮液的影响:含新型抗结核药物 - 钯配合物的聚合物微粒的情况

The influence of feedstock and process variables on the encapsulation of drug suspensions by spray-drying in fast drying regime: the case of novel antitubercular drug–palladium complex containing polymeric microparticles.

作者信息

Giovagnoli Stefano, Palazzo Francesco, Di Michele Alessandro, Schoubben Aurelie, Blasi Paolo, Ricci Maurizio

出版信息

J Pharm Sci. 2014 Apr;103(4):1255-68. doi: 10.1002/jps.23902.

Abstract

The purpose of this study was to address the effect of feedstock properties and process variables on the characteristics of antitubercular drug–palladium (Pd) containing poly(lactic) acid (PLA) microparticles (MP) obtained by spray-drying of noncolloidal particle dispersions in fast drying regime. Two different systems were compared: capreomycin–Pd (C–Pd) and ofloxacin–Pd (Ofx–Pd) dispersions in acetonitrile PLA solution. Particle size, dynamic light scattering, differential scanning calorimetry, SEM–energy dispersive X-ray, and spectrophotometric methods were used for MP characterization. C–Pd-loaded MP were optimized preliminarily by experimental design and compared with Ofx–Pd-loaded MP investigated in our previous work. Morphology of feedstock particles had a dominant role in determining MP morphology. The Charlesworth and Marshall theory was used to explain such behavior. The smaller and homogeneous C–Pd microparticulates favored MP inflation and buckling by forming a thick and nonporous shell. A percolation effect was proposed for the larger and irregular Ofx–Pd particles that produced smaller MP with a more porous shell. Increasing feedstock concentration led to higher particle loss. A tentative descriptive scheme of MP formation according to feedstock particle arrangement was proposed. This work suggested that spray-drying of drug dispersions should carefully consider the morphology of feedstock particles as a major parameter influencing final MP properties.

摘要

本研究的目的是探讨原料特性和工艺变量对通过在快速干燥条件下对非胶体颗粒分散体进行喷雾干燥所获得的含抗结核药物 - 钯(Pd)的聚乳酸(PLA)微粒(MP)特性的影响。比较了两种不同的体系:卷曲霉素 - 钯(C - Pd)和氧氟沙星 - 钯(Ofx - Pd)在乙腈PLA溶液中的分散体。使用粒度分析、动态光散射、差示扫描量热法、扫描电子显微镜 - 能量色散X射线和分光光度法对微粒进行表征。载有C - Pd的微粒通过实验设计进行了初步优化,并与我们之前工作中研究的载有Ofx - Pd的微粒进行了比较。原料颗粒的形态在决定微粒形态方面起主导作用。利用查尔斯沃思和马歇尔理论来解释这种行为。较小且均匀的C - Pd微粒通过形成厚且无孔的壳有利于微粒膨胀和屈曲。对于较大且不规则的Ofx - Pd颗粒,提出了一种渗滤效应,其产生具有更多孔壳的较小微粒。原料浓度的增加导致更高的颗粒损失。提出了一种根据原料颗粒排列的微粒形成的初步描述方案。这项工作表明,药物分散体的喷雾干燥应仔细考虑原料颗粒的形态,将其作为影响最终微粒性质的主要参数。

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