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首页> 外文期刊>Journal of pharmaceutical sciences. >An Extrusion Spheronization Approach to Enable a High Drug Load Formulation of a Poorly Soluble Drug with a Low Melting Surfactant
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An Extrusion Spheronization Approach to Enable a High Drug Load Formulation of a Poorly Soluble Drug with a Low Melting Surfactant

机译：挤出滚圆法可实现具有低熔点表面活性剂的难溶药物的高药物负荷配方

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Vitamin E tocopherol polyethylene glycol succinate (TPGS) is a non-ionic surface active agent, known to enhance the bioavailability of lipophilic compounds via wettability, solubility, and in some cases permeability enhancement. MK-0536 is an anti-retroviral drug with poor wettability and solubility and a high dose. Based on pharmacokinetic studies in dogs and humans, use of vitamin E TPGS in oral solid formulations of MK-0536 provides desired PK characteristics. The use of vitamin E TPGS, however, in solid dosage forms is limited because of the processing challenges resulting from its waxy nature and low melting temperature (approximate to 37 degrees C). The current study, for the first time, demonstrates the use of an alternative low pressure extrusion and spheronization approach to enable high loadings of the poorly soluble, poorly compactable drug and relatively high levels of vitamin E TPGS. This approach not only aided in mitigating processing challenges arising from most high energy process steps such as milling, compression, and coating, but also enabled a higher drug load formulation that provided superior bioperformance relative to a conventional high shear wet granulated formulation. An encapsulated dosage form consisting of pellets prepared by extrusion spheronization with 75% (w/w) MK-0536 and 10% (w/w) vitamin E TPGS was developed. (c) 2015 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:3752-3759, 2015
机译：维生素E生育酚聚乙二醇琥珀酸酯（TPGS）是一种非离子型表面活性剂，已知可通过润湿性，溶解性以及在某些情况下增强通透性来提高亲脂性化合物的生物利用度。 MK-0536是一种抗逆转录病毒药物，具有较差的润湿性和溶解性以及高剂量。基于在狗和人中的药代动力学研究，在MK-0536口服固体制剂中使用维生素E TPGS可提供所需的PK特性。然而，由于其蜡质性质和低熔融温度（约37℃）导致加工挑战，因此在固体剂型中维生素E TPGS的使用受到限制。当前的研究首次证明了使用另一种低压挤出和滚圆方法可以使难溶性，致密性差的药物和相对较高水平的维生素E TPGS大量装载。这种方法不仅有助于减轻大多数高能工艺步骤（例如研磨，压缩和涂覆）带来的加工挑战，而且还可以实现载药量更高的制剂，与常规的高剪切湿法制粒制剂相比，具有更高的生物性能。开发了由通过用75％（w / w）MK-0536和10％（w / w）维生素E TPGS挤出滚圆制备的小丸组成的胶囊剂型。 （c）2015年Wiley Periodicals，Inc.和美国药剂师协会J Pharm Sci 104：3752-3759，2015

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