(651d) Impact of Polyvinylpyrrolidone (PVP) on the Polymorphism of Succinic Acid Formed Via Monodisperse Droplet Evaporation

Particle structure, whether it is an amorphous form or one of multiple crystalline polymorphs, directly impacts the performance of crystalline products with applications in the food product and pharmaceutical industry. Based on the structure, the final product can have different behavior ranging from varied solubility and bioavailability to surface functionality. Additionally, morphology can impact surface properties or downstream processing ability. The formation of amorphous structures is often achieved by forming particles using the addition of a polymer excipients to the system. Sometimes, however, these polymer additives can impact the resulting polymorphism of the small molecule of interest, when the amount of polymer present is below the amount needed to form a fully amorphous particle. Previous work has shown that monodisperse droplet evaporation can be a valuable experimental method to study polymorphism of small molecule systems at room temperature, whereas spray drying typically takes place at notably elevated temperature.

In this work, we highlight our recent work on the quantified formation of the alpha polymorph of succinic acid, which is not stable at room temperature. The particles are generated through monodispersed droplet evaporation using a vibrating orifice aerosol generator. The resulting polymorphs are determined using powder X-ray diffraction (pXRD), and are quantified through comparison to standardized pXRD peak intensities. Through evaporation from isopropanol or ethanol the metastable alpha polymorph of succinic acid is not present; however, it is formed with the addition of low loadings of polyvinylpyrrolidone (PVP). The amount of alpha polymorph formed with a small PVP loading (< 5%) is greater for ethanol solutions compared to isopropanol solutions. However, both solutions reach an equivalent maximum amount of alpha present at levels of PVP > 10 wt%. We explain the polymorphic behavior based on PVP’s inhibition of solute nucleation, allowing the droplet to achieve higher levels of supersaturation before the crystals form. This inhibition reaches a maximum due to thermodynamic limitations. Further, through evaporation from methanol solutions, the alpha polymorph is dominant, and increasing the amount of PVP in the solution slowly decreases the amount of alpha present. This behavior is explained based on the hydrogen bonding donating capability of methanol relative to ethanol and isopropanol. Further, the addition of PVP reduces the impact of that hydrogen bond donating ability due to it being a hydrogen bond acceptor. Finally, we will discuss the resulting particle morphologies as well as the potential of this work to extend to more general methods to understand polymorph formation of similar systems.