Lopes Diogo G, Becker Karin, Stehr Michael, Lochmann Dirk, Haack Detlev, Zimmer Andreas, Salar-Behzadi Sharareh
Research Center Pharmaceutical Engineering GmbH, Graz, Austria; Karl-Franzens-University Graz, Department of Pharmaceutical Technology, Graz, Austria.
Karl-Franzens-University Graz, Department of Pharmaceutical Technology, Graz, Austria.
J Pharm Sci. 2015 Dec;104(12):4257-4265. doi: 10.1002/jps.24660. Epub 2015 Sep 30.
Hot-melt coating is of growing interest, because it does not require solvents, resulting in reduced process times and costs. However, excipients for this technology are mainly triacylglycerides (TAGs) or their derivatives, which exhibit polymorphism, surface disruption, and complex crystallite networks, affecting the release profile of produced microcapsules. In this work, anhydrous citric acid crystals were coated with molten tristearin using conventional inlet air temperatures (microcapsules A) and temperatures above the melting point of α-form (microcapsules B). Additionally, microcapsules A were tempered to achieve polymorphic stability (microcapsules AB). The product yield and coating efficacy were above 90% and 97%, respectively, demonstrating the feasibility and efficacy of the process. Small angle X-ray scattering analysis confirmed that the tristearin shell of microcapsules B is in the β-form with a larger average crystallite size than microcapsules A and AB. Scanning electron microscopy images revealed a nonbloomed surface of microcapsules B. We showed that blooming does not play a critical role in the drug release, but the apparent diffusion coefficient of drug is dramatically reduced by increasing TAGs crystallite size and resulting tortuosity. This work brings new insights on the micrometric properties of solid lipid dosage forms, being an important step to prevent the overuse of excipients with unknown toxicity.
热熔包衣越来越受到关注，因为它不需要溶剂，从而减少了加工时间和成本。然而，这项技术的辅料主要是三酰甘油（TAGs）或其衍生物，它们具有多晶型性、表面破坏和复杂的微晶网络，会影响所生产微胶囊的释放曲线。在这项工作中，使用传统的进气温度（微胶囊A）和高于α晶型熔点的温度（微胶囊B），用熔融的硬脂酸甘油酯对无水柠檬酸晶体进行包衣。此外，对微胶囊A进行调温以实现多晶型稳定性（微胶囊AB）。产品收率和包衣效率分别高于90%和97%，证明了该工艺的可行性和有效性。小角X射线散射分析证实，微胶囊B的硬脂酸甘油酯外壳为β晶型，平均微晶尺寸比微胶囊A和AB大。扫描电子显微镜图像显示微胶囊B的表面没有起霜。我们表明，起霜在药物释放中不起关键作用，但通过增加TAGs微晶尺寸和由此产生的曲折度，药物的表观扩散系数会显著降低。这项工作为固体脂质剂型的微观性质带来了新的见解，是防止过度使用具有未知毒性的辅料的重要一步。
