Stability, Structure, and Morphology of Dicarboxylic Acid Particles with Polymer Excipients Synthesized VIA Monodisperse Droplet Evaporation

In the pharmaceutical industry, properties such as structure and stability are very important. Many new drugs show low water solubility/bioavailability (the amount of a drug absorbed by the body). Altering a particle’s structure is one way to solve this issue (Van Zee et al., 2020). Particles can have several structures: crystalline (ordered arrangement of molecules), amorphous (random ordering of molecules), or semi-crystalline (mix between crystalline and amorphous). Amorphous particles tend to exhibit greater water solubility but may crystallize over time. Conversely, crystalline particles typically are less water soluble but are more stable. Many compounds have several crystal structures depending on formation conditions. Each of these unique crystal structures is called a polymorph. The properties of an active pharmaceutical ingredient (API) can vary between polymorphs, making them of great importance to the pharmaceutical industry. Particles contain two components: an API and a polymer excipient. Excipients are inactive ingredients that influence structure, stability, and other properties. Moreover, the ratio of API to excipient has an impact on the particles’ structure: at very low ratios, stable amorphous particles form; at higher ratios, amorphous particles form that partially crystallize over time; and at the highest ratios, partially crystalline particles form (Vostal, 2018).

This work focuses on two main areas: (1) creating initially amorphous particles and quantifying the amount of recrystallization over time and (2) forming partially crystalline particles and quantifying the amounts of each polymorph present. Particles will be made using adipic acid or succinic acid as the model APIs with poly(vinylpyrrolidone) (PVP) as the excipient. These compounds are chosen since PVP is a common excipient in many pharmaceuticals and dicarboxylic acids resemble many APIs. The Vibrating Orifice Aerosol Generator (VOAG) is used to form the particles in this study, which works like a spray drier, but at ambient conditions eliminating the effects of temperature. The particles are monitored using powder x-ray diffraction (pXRD) and scanning electron microscopy (SEM). Standards of known crystallinity are made using a spray dryer to quantify the amount of crystallization that occurs or the amount of each polymorph present.

Van Zee, N. J., M. A. Hillmyer, and T. P. Lodge, “Role of Polymer Excipients in the Kinetic Stabilization of Drug-Rich Nanoparticles.” ACS Applied Bio Materials, 3, no. 10, (2020): 7243-7254. https://doi.org/10.1021/acsabm.0c01173.

Vostal, K. “Stability of Amorphous Particles Formed Via Monodisperse Droplet Evaporation.” 2018.