Precipitation dominated thin films of acetaminophen fabricated by meniscus guided coating

Abstract

Recently, meniscus-guided coating (MGC) has been utilized for small molecule pharmaceutical crystallization and has demonstrated the ability to direct the formation of crystal polymorphs. However, the traditional coating regimes (evaporative and Landau–Levich) do not provide adequate control over the crystal size or shape – specifically the formation of small and low-aspect ratio crystallites is desirable for pharmaceutical applications. In this work, MGC processing conditions are adjusted to achieve three distinct film morphologies of acetaminophen from aqueous solutions. The morphologies are characterized using polarized optical microscopy and scanning electron microscopy. Notably, we identified a set of processing conditions that results in uniform microcrystal formation due to rapid evaporation and precipitation. Deposits created with this technique produce crystallites with an average diameter of 6.9 ± 2.4 μm with nearly monodisperse size distributions. X-ray diffraction was used to assess polymorphism and crystal texture in the thin films as a function of processing conditions, revealing that the microcrystals are heterogeneously nucleated and preferentially oriented on the substrate. This work contributes new insight to processing techniques which may be relevant to continuous pharmaceutical manufacturing efforts by obtaining preferred morphologies.