(184p) Impact of Droplet Evaporation on Polymorphism of Suberic Acid

In the diverse landscape of the pharmaceutical sector, which presents its own mix of challenges and opportunities, the significance of polymorphism is highlighted as the industry continues to expand and active ingredients become more complex. Polymorphism in a drug compound signifies its capacity to adopt various crystal forms. Variations in polymorphic forms of drug compounds can significantly impact bioavailability, solubility, stability, and efficacy, posing substantial challenges in drug formulation and regulatory compliance. To overcome these challenges and enhance drug development and formulation, implementing a polymorph screening process is essential. This process involves identifying and characterizing the different solid-state forms that a drug molecule can adopt, including various crystal structures, hydrates, and amorphous forms. Despite the high and consistent loss rate of drug candidates, conducting thorough screening is costly and time-consuming. However, it is crucial to select the appropriate polymorph to address stability and physicochemical properties. Carboxyl group-containing organic compounds are extensively used across a wide range of applications within the pharmaceutical industry. This work aims to investigate the polymorphism of suberic acid (C₈H1₄O₄), a dicarboxylic acid utilized in drug synthesis and as a pharmaceutical co-former, with a specific focus on the influence of crystallization conditions, including solvent choice, concentration all using a droplet evaporation technique. While suberic acid has been studied extensively its polymorphism has been only a more recent focus with only two polymorphs of suberic acid identified. In this work, we present a potential third polymorph that is formed through droplet evaporation.

A constant output aerosol generating atomizer is used to create a microparticles of suberic acid from solution via droplet evaporation at room temperature. Polydisperse droplets containing suberic acid particles are subjected to drying in a series of dryer columns to evaporate the solvent. In this study, various solvents including water, ethanol, and isopropyl alcohol were used at different droplet concentrations. The impact of variations in crystallization conditions on suberic acid polymorph formation was investigated to determine the conditions for successful polymorph isolation. Suberic acid particles undergo analysis utilizing a combination of techniques. X-ray Diffraction (XRD) examines the internal crystalline structure via diffraction patterns, while Scanning Electron Microscopy (SEM) investigates sample morphology, including size, shape, and surface characteristics. General Scanning Mobility Particle Size (SMPS) determines particle size distribution, and Differential Scanning Calorimetry (DSC) analyzes polymorphic transformations and thermal transitions.