Effect of Polymer Excipient on Metastable Succinic Acid Particle Formation Via Monodisperse Droplet Evaporation

2017 AIChE Annual Meeting

Ted Egnaczyk and Dr. Ryan C. Snyder

The crystallization tendencies of Active Pharmaceutical Ingredients (API) have a great impact on their properties, uses, and drug performance. There are several characteristics of these molecules of interest that directly affect their bioavailability in the body, and therefore their effectiveness. One of which is water solubility. As new pharmaceutical compounds are continually created, the active ingredients have increased in complexity, tending towards decreased water solubility, and in turn decreasing bioavailability in the body. One method of positively influencing the water solubility of model API ingredients is through forming amorphous dispersions. One way to form amorphous dispersions, and to create more energetic metastable polymorphs, is by including a polymer additive in solution. Including a polymer additive, or excipient, in a given formulation is known to influence the polymorph that is formed. Additionally, relatively small amounts of polymer excipient in solution may create a large variation in the crystallization tendencies of a model API compound.

Succinic acid is used as the model organic compound in this study. This dicarboxylic acid has a very high propensity to crystallize. Succinic acid is very well studied and there exists significant data to compare results. This molecule is known to have two metastable polymorphs, alpha-succinic acid and beta-succinic acid. The addition of polyvinylpyrrolidone (PVP) as a polymer excipient was shown in the past to cause the formation of the alpha form of succinic acid. A polymer excipient’s purpose is to disrupt the regular crystallization patterns of a molecule and cause metastable polymorphs to form or the particle to become amorphous. Monodisperse droplet evaporation is implemented using a Vibrating Orifice Aerosol Generator (VOAG). In this context, the formation of succinic acid’s alpha metastable polymorph was studied as a function of the amount of PVP polymer excipient added. Scanning Electron Microscopy (SEM) and X-Ray Diffractometer (XRD) are used to investigate the morphology and identity of metastable succinic acid polymorphs present in each processed sample. Isopropyl alcohol is used as the solvent for all particle solutions. In this work, I look to quantify the impact of PVP by considering the amount of it required to form the alpha metastable polymorph.