Cavallari Cristina, Gonzalez-Rodriguez Marisa, Tarterini Fabrizio, Fini Adamo
Department FABIT, University of Bologna, Bologna, Italy.
Department of Pharmaceutical Chemistry and Technology, University of Seville, Seville, Spain.
Eur J Pharm Biopharm. 2014 Nov;88(3):909-18. doi: 10.1016/j.ejpb.2014.08.014. Epub 2014 Sep 11.
Nine systems were prepared containing Gelucire 50/13 and various amounts (9-18-36-45% w/w) of Lutrol F68 and F127 in the presence and in the absence of 10% w/w of olanzapine and formulated as a solid dispersion in the form of microspheres by ultrasound (US)-assisted spray congealing. Thermal analysis, using differential scanning calorimetry (DSC) and thermomicroscopy (HSM), suggested the presence of particles of reduced size of olanzapine precipitated inside the microspheres. The microspheres were also studied by means of electron microscopy (SEM) for their shape and aspect, by some image analysis parameters (fractal dimension) and using Energy-dispersive X-ray (X-EDS) and micro-Raman spectroscopy to qualitatively evaluate the composition of different points of the surface. The surface of the microspheres displayed a non-homogeneous distribution of the drug by the presence of wart-like protuberances, whose number increases as the Lutrol content of the systems increases. The same systems in the absence of US, obtained after cooling the molten mixtures, lack these structures and only a very few of them can be found. The blooming of the surface was hypothesized as related to crystallization or phase de-mixing or lipid component diffusion of the carrier mixture inside the cooling mass subjected to ultrasound vibration. Ultrasounds accelerate the physical changes concerning carriers and drug, outlining the importance of ultrasound to achieve stability for formulations of this type. The microspheres de-aggregate on contact with the dissolution medium and release the drug with a bimodal mode according to the Lutrol content.
制备了九个系统，其中包含Gelucire 50/13以及不同含量（9% - 18% - 36% - 45% w/w）的 Lutrol F68和F127，分别在存在和不存在10% w/w奥氮平的情况下，通过超声辅助喷雾冷凝法将其制成微球形式的固体分散体。使用差示扫描量热法（DSC）和热显微镜（HSM）进行热分析，结果表明微球内部存在尺寸减小的奥氮平沉淀颗粒。还通过电子显微镜（SEM）研究了微球的形状和外观，通过一些图像分析参数（分形维数）以及使用能量色散X射线（X - EDS）和显微拉曼光谱对表面不同点的组成进行定性评估。微球表面由于存在疣状突起而显示出药物的非均匀分布，随着系统中 Lutrol 含量的增加，这些突起的数量也会增加。在不使用超声的情况下冷却熔融混合物后得到相同的系统，但缺乏这些结构，只能发现极少数。推测表面的起霜现象与冷却过程中受到超声振动的物料内部载体混合物的结晶、相分离或脂质成分扩散有关。超声加速了与载体和药物相关的物理变化，凸显了超声对于实现此类制剂稳定性的重要性。微球与溶解介质接触时会解聚，并根据 Lutrol 含量以双峰模式释放药物。
