Ordered Submicrometer Structures Developed by Directional Evaporative Crystallization of Acetaminophen in the Presence of Polymers

Abstract

Crystallization engineering is crucial for the preparation of drug delivery systems with precise release behavior and improved stability. Although evaporation has been commonly used to prepare pharmaceutical film formulations, controlled evaporative crystallization to achieve uniform crystal size and shape has rarely been investigated. In this study, ordered submicrometer composite structures of acetaminophen (ACM) and polymers were prepared via directional evaporative crystallization controlled by a temperature gradient. The ACM crystals had submicrometer sizes while retaining the original crystal polymorph and were aligned along the direction of the temperature gradient, resulting in line structures having branches with uniform and oriented crystal structures. Although the use of a polymer did not affect conventional oven-crystallized films, it significantly decreased the melting point and heat of fusion of directionally crystallized films. The formation of ordered submicrometer composite structures must rely more on kinetic parameters than thermodynamic parameters since no significant intrinsic molecular interactions were discovered. A wide range of sustained-release characteristics could be obtained depending on the polymer types. This unique fast directional crystallization method could offer a new opportunity for future film delivery systems.