Department SMETEC, University of Bologna, Bologna, Italy.
J Pharm Sci. 2010 Oct;99(10):4251-60. doi: 10.1002/jps.22146.
Olanzapine was formulated as 10% (w/w) mixture with cutina to which stearic acid was added, ranging from 10% to 90% (w/w) of the total mass to control the drug release. The molten mixtures were processed by ultrasound-assisted spray-congealing technique, obtaining solid microspheres. The drug is stable under these conditions and only a partial miscibility in the solid state was observed by DSC between the two fatty materials with two separated melting endotherms in the thermograms: this can be due to the presence of two phases inside the solid dispersion. Olanzapine is distributed into the two phases according to its partition coefficient: two phases make the system less suitable to crystallization of the drug; the loading of the drug could reach saturation with difficulty and the rate of the olanzapine release is differentiated, since the drug is released from two different carriers. Dissolution profiles suggest occurrence of a bimodal release, where each portion of the release profile is linear and the slope increases with a higher content of stearic acid in the carrier mixture, that behaves as a release promoter. Tests were also carried out with palmitic and lauric acids for comparison and also for systems in the absence of ultrasound.
奥氮平被配制成 10%（重量/重量）与角质的混合物，其中加入了从 10%到 90%（重量/重量）的硬脂酸，以控制药物释放。熔融混合物通过超声辅助喷雾凝固技术进行处理，得到固体微球。在这些条件下，药物是稳定的，只有通过 DSC 在两种脂肪材料之间观察到部分混溶性，在热谱图中有两个单独的熔融吸热峰：这可能是由于固分散体内部存在两个相。奥氮平根据其分配系数分布在两个相中：两个相使系统不太适合药物结晶；药物的负载很难达到饱和，并且药物的释放速率也不同，因为药物是从两种不同的载体中释放出来的。溶解曲线表明存在双峰释放，其中释放曲线的每个部分都是线性的，斜率随着载体混合物中硬脂酸含量的增加而增加，硬脂酸作为释放促进剂。还进行了棕榈酸和月桂酸的测试进行比较，也进行了没有超声的系统的测试。
