Department of Pharmaceutical Sciences, Ferrara University, 44121, Ferrara, Italy.
AAPS J. 2009 Dec;11(4):771-8. doi: 10.1208/s12248-009-9148-6. Epub 2009 Nov 12.
A solid lipid microparticle system containing budesonide was prepared by oil in water emulsification followed by spray drying. The solid lipid system was studied in terms of morphology, particle size distribution, crystallinity, thermal properties, aerosol performance, and dissolution/diffusion release. The microparticle system was also compared to conventional spray-dried crystalline and amorphous budesonide samples. The particle size distributions of the crystalline, amorphous, and solid lipid microparticles, measured by laser diffraction, were similar; however, the microparticle morphology was more irregular than the spray-dried drug samples. The thermal response of the solid lipid microparticles suggested polymorphic transition and melting of the lipid, glycerol behenate (at approximately 48 degrees C and approximately 72 degrees C). No budesonide melting or crystallisation peaks were observed, suggesting that the budesonide was integrated into the matrix. X-ray powder diffraction patterns of the crystalline and amorphous budesonide were consistent with previous studies while the solid lipid microparticles showed two peaks, at approximately 21.3 and 23.5 2theta suggesting the metastable sub-alpha and primarily beta' form. Analysis of the in vitro diffusion/dissolution of the formulations was studied using a flow through model and curves analysed using difference/similarity factors and fitted using the Higuchi model. Regression analysis of this data set indicated differences in the t (0.5), where values of 49.7, 35.3, and 136.9 min were observed for crystalline, amorphous, and the solid lipid microparticles, respectively. The aerosol performance (<5 microm), measured by multistage liquid impinger, was 29.5%, 27.3%, and 21.1 +/- 0.6% for the crystalline, amorphous, and the solid lipid microparticles, respectively. This study has shown that solid lipid microparticles may provide a useful approach to controlled release respiratory therapy.
通过油包水乳化法和喷雾干燥法制备了一种含有布地奈德的固体脂质微粒子系统。从形态、粒径分布、结晶度、热性能、气溶胶性能和溶解/扩散释放等方面对固体脂质系统进行了研究。并将该微粒子系统与常规喷雾干燥的结晶态和无定形态布地奈德样品进行了比较。通过激光衍射测量，结晶态、无定形态和固体脂质微粒子的粒径分布相似；然而，微粒子形态比喷雾干燥的药物样品更不规则。固体脂质微粒子的热响应表明，脂质甘油二十二酸酯发生多晶型转变和熔化（约 48°C 和约 72°C）。未观察到布地奈德的熔化或结晶峰，表明布地奈德已融入基质中。结晶态和无定形态布地奈德的 X 射线粉末衍射图谱与先前的研究一致，而固体脂质微粒子则显示出两个峰，约为 21.3 和 23.5 2θ，表明亚稳的 sub-alpha 和主要的 beta' 形式。使用流动模型对制剂的体外扩散/溶解进行了分析，并使用差异/相似因子对曲线进行了分析，然后使用 Higuchi 模型进行了拟合。对该数据集的回归分析表明，t (0.5) 值存在差异，结晶态、无定形态和固体脂质微粒子分别为 49.7、35.3 和 136.9 min。通过多阶段液体撞击器测量的气溶胶性能（<5 µm）分别为 29.5%、27.3%和 21.1 +/- 0.6%，对于结晶态、无定形态和固体脂质微粒子。这项研究表明，固体脂质微粒子可能为控制释放呼吸治疗提供一种有用的方法。
