Banerjee Manali, Brettmann Blair
School of Materials Science and Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA.
School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA.
Pharmaceutics. 2020 Oct 20;12(10):995. doi: 10.3390/pharmaceutics12100995.
Poor water solubility is one of the major challenges to the development of oral dosage forms containing active pharmaceutical ingredients (APIs). Polymorphism in APIs leads to crystals with different surface wettabilities and free energies, which can lead to different dissolution properties. Crystal size and habit further contribute to this variability. An important focus in pharmaceutical research has been on controlling the drug form to improve the solubility and thus bioavailability of APIs. In this regard, heterogeneous crystallization on surfaces and crystallization under confinement have become prominent forms of controlling polymorphism and drug crystal size and habits; however there has not been a thorough review into the emerging field of combining these approaches to control crystallization. This tutorial-style review addresses the major advances that have been made in controlling API forms using combined crystallization methods. By designing templates that not only control the surface functionality but also enable confinement of particles within a porous structure, these combined systems have the potential to provide better control over drug polymorph formation and crystal size and habit. This review further provides a perspective on the future of using a combined crystallization approach and suggests that combining surface templating with confinement provides the advantage of both techniques to rationally design systems for API nucleation.
水溶性差是含活性药物成分（API）的口服剂型开发面临的主要挑战之一。API的多晶型会导致晶体具有不同的表面润湿性和自由能，进而导致不同的溶解特性。晶体大小和晶习进一步加剧了这种变异性。药物研究的一个重要重点是控制药物形态，以提高API的溶解度，从而提高其生物利用度。在这方面，表面上的异质结晶和受限条件下的结晶已成为控制多晶型以及药物晶体大小和晶习的重要形式；然而，对于将这些方法结合起来控制结晶的新兴领域，尚未有全面的综述。本教程式综述阐述了使用组合结晶方法在控制API形态方面取得的主要进展。通过设计不仅能控制表面功能，还能使颗粒受限在多孔结构内的模板，这些组合系统有可能更好地控制药物多晶型的形成以及晶体大小和晶习。本综述进一步展望了使用组合结晶方法的未来，并指出将表面模板化与受限条件相结合具有两种技术的优势，能够合理设计API成核系统。
