349692 Direct Formulation of Succinic Acid Amorphous Dispersions Via Monodisperse Droplet Evaporation
Direct Formulation of Succinic Acid Amorphous Dispersions via
Monodisperse Droplet Evaporation
Luke P. Webster
Advisor: Dr. Ryan C. Snyder
Department of Chemical Engineering, Bucknell University
As pharmaceutical companies continually search for new compounds, pharmaceutical ingredients are becoming more complex and often trend towards less water solubility, and accordingly, less bioavailability. This trending decrease in bioavailability is increasing the importance of drug delivery and processing technology. For solid products, one way of improving bioavailability is to utilize modifications to the solid state organic structure. By utilizing high energy, amorphous dispersions, the kinetics of dissolution of a molecule into the body can be improved. The ability to produce amorphous phases from numerous production methods is well documented; however, an understanding of the conditions that lead to formation of amorphous structures is not. Previous work has shown that creation of less stable forms is enhanced using monodisperse droplet generation. With this in mind, research into the factors that affect the formation of amorphous structures using monodisperse droplet evaporation at room temperature are investigated.
Succinic acid is the model organic compound in this study. Due to its high propensity to crystallize, succinic acid provides a challenging compound in which to create an amorphous phase. Additionally, the well-studied nature of the molecule’s crystallization properties provides wide applicability of the work as well as significant data for comparison. Preliminary studies indicated that polymer excipients like polyvinylpyrrolidone (PVP) produce a larger effect on the structure of succinic acid than small molecule excipients like mannitol. In this context, the structure and morphology of succinic acid particles are studied as a function of solvent, composition, and molecular weight of polymer additive. Purely amorphous succinic acid is created at succinic acid concentrations between 31.25wt% and 25wt% succinic acid with a balance of PVP in isopropanol and ethanol solutions via spray drying in a vibrating orifice aerosol generator (VOAG) at room temperature. The effect of solvent on the structure of succinic acid is negligible; however an effect of solvent on morphology is evident. The molecular weight of the polymer additive is not found to affect structure or morphology of the particles. Future efforts in this work could consider additional polymer molecular weights or a more thorough understanding of the underlying thermodynamics of the mixtures.
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