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Design of Olanzapine/Lutrol Solid Dispersions of Improved Stability and Performances

机译:改善了稳定性和性能的奥氮平/ Lutrol固体分散体的设计

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摘要

Eleven solid dispersions containing olanzapine, with carriers of different composition (Lutrol® F68, Lutrol® F127, Gelucire® 44/14), were prepared and examined by thermal (differential scanning calorimetry (DSC); thermomicroscopy (HSM)) and X-ray diffraction (XRD) analysis, both as fresh or aged (one year) samples. Drug and carriers were preliminarily selected in order to avoid problems related to the aging of the formulation, according to the solubility parameters of carriers and drug. These parameters make it possible to predict the low solubility of olanzapine in the carriers (alone or in mixtures). Systems containing only Lutrol (also in the presence of Transcutol®) contain the drug in the form of particles of reduced size and in a crystalline form. Gelucire® 44/14 apparently increases the amount of olanzapine dissolved in the solid carrier, but this is presumed to be a metastable state, probably related to the heterogeneous nature of the carrier that delays crystallization of the drug. The high hydrophilicity of the carriers proves suitable to an accelerated and quick release of the drug regardless of aging. Differences in the release profiles between Lutrol- and Gelucire-containing systems were interpreted in terms of the formation of polymer micelles by the Lutrols when in aqueous solution.
机译:制备了11种含奥氮平的固体分散体,其载体具有不同的组成(Lutrol ® F68,Lutrol ® F127,Gelucire ® 44/14)。并通过热(差示扫描量热法(DSC);热显微镜(HSM))和X射线衍射(XRD)分析进行检查,无论是新鲜样品还是陈化样品(一年)。为了避免与制剂老化有关的问题,根据载体和药物的溶解度参数,预先选择了药物和载体。这些参数使预测奥氮平在载体(单独或混合物)中的低溶解度成为可能。仅包含Lutrol的系统(也在Transcutol ®的情况下)包含尺寸减小的颗粒形式和结晶形式的药物。 Gelucire ® 44/14显然会增加奥氮平在固体载体中的溶解量,但这被认为是亚稳定状态,可能与延迟药物结晶的载体的异质性有关。载体的高亲水性被证明适合于加速和快速释放药物,而与衰老无关。含Lutrol和Gelucire的系统之间释放曲线的差异是根据Lutrols在水溶液中形成的聚合物胶束来解释的。

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