Wolska Eliza, Sznitowska Małgorzata, Krzemińska Katarzyna, Ferreira Monteiro Maria
Department of Pharmaceutical Technology, Medical University of Gdansk, Hallera 107, 80-416 Gdansk, Poland.
The Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal.
Pharmaceutics. 2020 Jul 15;12(7):664. doi: 10.3390/pharmaceutics12070664.
Solid lipid microparticles (SLM) can be presented as liquid suspension or spray-dried powder. The main challenge in SLM technology is to precisely determine the location of the active substance (API) in the different compartments of the formulation and its changes during SLM processing. Therefore, the purpose of the research was to assess the distribution of the API and to investigate the nature of the API-lipid interaction when the formulation was subjected to spray drying, with an indication of the most suitable techniques for this purpose. SLM were prepared with two various lipids (Compritol or stearic acid) and two model APIs: cyclosporine (0.1% and 1% ) and spironolactone (0.1% and 0.5% ). Physicochemical characterizations of the formulations, before and after spray drying, were performed by differential scanning calorimetry (DSC), atomic force microscopy (AFM), Raman spectroscopy and nuclear magnetic resonance (NMR). The API distribution between the SLM matrix, SLM surface and the aqueous phase was determined, and the release study was performed. It was demonstrated that, in general, the spray drying did not affect the drug release and drug distribution; however, some changes were observed in the SLM with Compritol and when the API concentration was lower. Only in the SLM with stearic acid was a change in the DSC curves noted. Measurements with the AFM technique proved to be a useful method for detecting differences in the surface properties between the placebo and API-loaded SLM, while the Raman spectroscopy did not show such evident differences.
固体脂质微粒（SLM）可以制成液体悬浮液或喷雾干燥粉末。SLM技术的主要挑战在于精确确定活性物质（原料药，API）在制剂不同组分中的位置及其在SLM加工过程中的变化。因此，本研究的目的是评估原料药的分布，并研究制剂进行喷雾干燥时原料药与脂质相互作用的性质，同时指出最适合此目的的技术。使用两种不同的脂质（Compritol或硬脂酸）和两种模型原料药制备了SLM：环孢素（0.1%和1%）和螺内酯（0.1%和0.5%）。通过差示扫描量热法（DSC）、原子力显微镜（AFM）、拉曼光谱和核磁共振（NMR）对喷雾干燥前后的制剂进行了物理化学表征。测定了SLM基质、SLM表面和水相之间的原料药分布，并进行了释放研究。结果表明，一般来说，喷雾干燥不影响药物释放和药物分布；然而，在含有Compritol的SLM中以及原料药浓度较低时观察到了一些变化。仅在含有硬脂酸的SLM中，DSC曲线出现了变化。AFM技术测量被证明是检测安慰剂和载有原料药的SLM表面性质差异的有用方法，而拉曼光谱未显示出如此明显的差异。
