School of Pharmacy, University of Eastern Finland, Kuopio, Finland.
Department of Pharmacy, University of Copenhagen, Denmark.
Int J Pharm. 2017 Oct 30;532(1):1-12. doi: 10.1016/j.ijpharm.2017.08.123. Epub 2017 Sep 1.
Amorphous solid dispersions (ASDs) are probably the most common and important supersaturating drug delivery systems for the formulation of poorly water-soluble compounds. These delivery systems are able to achieve and maintain a sustained drug supersaturation which enables improvement of the bioavailability of poorly water-soluble drugs by increasing the driving force for drug absorption. However, ASDs often require a high weight percentage of carrier (usually a hydrophilic polymer) to ensure molecular mixing of the drug in the carrier and stabilization of the supersaturated state, often leading to high dosage volumes and thereby challenges in the formulation of the final dosage form. As a response to the shortcomings of the ASDs, the so-called co-amorphous formulations, which are amorphous combinations of two or more low molecular weight components, have emerged as an alternative formulation strategy for poorly-soluble drugs. While the current research on co-amorphous formulations is focused on preparation and characterization of these systems, more detailed research on their supersaturation and precipitation behavior and the effect of co-formers on nucleation and crystal growth inhibition is needed. The current status of this research is reviewed in this paper. Furthermore, the potential of novel preparation methods for co-amorphous systems with respect to the current preparation methods are discussed.
无定形固体分散体（ASD）可能是最常见和最重要的超饱和药物传递系统，用于制备水溶性差的化合物。这些传递系统能够实现并维持持续的药物超饱和度，通过增加药物吸收的驱动力来提高水溶性差的药物的生物利用度。然而，ASD 通常需要高重量百分比的载体（通常是亲水性聚合物），以确保药物在载体中的分子混合和超饱和状态的稳定，这通常会导致高剂量体积，从而给最终剂型的制剂带来挑战。为了应对 ASD 的缺点，所谓的共无定形制剂应运而生，这是两种或多种低分子量成分的无定形组合，是一种用于水溶性差药物的替代制剂策略。虽然目前对共无定形制剂的研究集中在这些系统的制备和表征上，但需要对它们的过饱和和沉淀行为以及共晶形成剂对成核和晶体生长抑制的影响进行更详细的研究。本文综述了这方面的研究现状。此外，还讨论了新型共无定形系统制备方法相对于现有制备方法的潜力。
