Chatterjee Bappaditya, Reddy Abhishek, Santra Moushami, Khamanga Sandile
Shobhaben Pratapbhai Patel School of Pharmacy and Technology Management, SVKM's NMIMS, Mumbai 400056, India.
Faculty of Pharmacy, Rhodes University, Makhanda 6140, South Africa.
Pharmaceutics. 2022 May 3;14(5):983. doi: 10.3390/pharmaceutics14050983.
Amorphous solid dispersion is a popular formulation approach for orally administered poorly water-soluble drugs, especially for BCS class II. But oral delivery could not be an automatic choice for some drugs with high first-pass metabolism susceptibility. In such cases, transdermal delivery is considered an alternative if the drug is potent and the dose is less than 10 mg. Amorphization of drugs causes supersaturation and enhances the thermodynamic activity of the drugs. Hence, drug transport through the skin could be improved. The stabilization of amorphous system is a persistent challenge that restricts its application. A polymeric system, where amorphous drug is dispersed in a polymeric carrier, helps its stability. However, high excipient load often becomes problematic for the polymeric amorphous system. Coamorphous formulation is another approach, where one drug is mixed with another drug or low molecular weight compound, which stabilizes each other, restricts crystallization, and maintains a single-phase homogenous amorphous system. Prevention of recrystallization along with enhanced skin permeation has been observed by the transdermal coamorphous system. But scalable manufacturing methods, extensive stability study and in-depth in vivo evaluation are lacking. This review has critically studied the mechanistic aspects of amorphization and transdermal permeation by analyzing recent researches in this field to propose a future direction.
无定形固体分散体是口服难溶性药物，尤其是BCS II类药物常用的一种制剂方法。但对于一些具有较高首过代谢敏感性的药物来说，口服给药并非必然选择。在这种情况下，如果药物活性高且剂量小于10毫克，经皮给药被视为一种替代方案。药物的无定形化会导致过饱和并增强药物的热力学活性。因此，药物透过皮肤的传输可以得到改善。无定形体系的稳定性是一个长期存在的挑战，限制了其应用。在聚合物体系中，无定形药物分散在聚合物载体中，有助于提高其稳定性。然而，对于聚合物无定形体系来说，高辅料用量往往会带来问题。共无定形制剂是另一种方法，即一种药物与另一种药物或低分子量化合物混合，它们相互稳定，限制结晶，并维持单相均匀的无定形体系。经皮共无定形体系已观察到能防止重结晶并增强皮肤渗透。但目前缺乏可扩展的制造方法、广泛的稳定性研究和深入的体内评价。本综述通过分析该领域的最新研究，对无定形化和经皮渗透的机理进行了批判性研究，以提出未来的发展方向。
