Characterization of Dicarboxylic Acids Via Scanning Electron Microscopy and X-Ray Powder Diffraction

Characterization of Dicarboxylic Acids via Scanning Electron Microscopy and X-Ray Powder Diffraction

2016 AIChE Annual Meeting

Kurt R. Vostal and Ryan C. Snyder

            As the pharmaceutical industry continues to expand, active ingredients continue to become more complex, often causing difficulty implementing compounds into an effective pharmaceutical due to a decrease in water solubility.  On the other hand, drug delivery techniques and processing technologies continue to develop as to increase the bioavailability of more complex active ingredients.  Bioavailability is the rate at which a substance is absorbed into the body and made available for physiological activity.  The crystal structure of solid organic products can be modified to an amorphous state as to increase the compound’s solubility in water and thus its bioavailability.  While this method of increasing bioavailability has been studied extensively, the conditions at which solid organic compounds are transitioned to an amorphous state are more unknown.  Carboxylic Acids, or organic compounds containing a carboxyl group, are used in a wide variety of applications and continue to be an essential compound within the pharmaceutical industry.  Specifically, carboxylic acids are an active ingredient in a number of different medications, ranging from aspirins to and ointments.  This work makes use of monodisperse droplet evaporation technology in order to investigate the formation of less stable amorphous structures of carboxylic acids at room temperature.

            A Vibrating Orifice Aerosol Generator (VOAG) is used to create monodispersed droplets of a solution containing a potential active ingredient and an excipient that prevents the crystallization of the active ingredient.  Liquid droplets lead to the rapid evaporation of the solvent, making the formation of amorphous structures more likely.  In this study, the solvent isopropyl alcohol is used, leaving the active ingredient succinic acid in the amorphous phase due to the use of a polyvinylpyrrolidone (PVP) excipient.  Succinic Acid and PVP ratios are varied in order to determine the concentrations at which amorphous succinic acid formation is most successful.  The VOAG creates droplets of uniform size, and thus active ingredients in the amorphous phase can be analyzed on the basis of structure and morphology alone. Both Scanning Electron Microscopy (SEM) and X-Ray Powder Diffraction (XRD) are used to investigate the particle morphology and the particle structure respectively.  The stability of the amorphous structures is also considered.