389128 Formation of Metastable Polymorphs and Amorphous Structures through Monodisperse Droplet Evaporation

Wednesday, November 19, 2014: 1:36 PM
301 (Hilton Atlanta)
Luke P. Webster and Ryan C. Snyder, Chemical Engineering, Bucknell University, Lewisburg, PA

Particle structure and morphology are two important product characteristics of organic molecular compounds with specific applications to the food product and pharmaceutical industries.  The structure, whether it is multiple crystalline polymorphs or amorphous forms, directly impacts the performance of the final product because of changes in bioavailability and surface functionality (Bernstein, 2002).  The morphology typically affects downstream processes such as filtering and drying.  Formation of metastable polymorphs or amorphous structures is often achieved through the addition of polymer excipients or other additives to the system.  However, a more fundamental understanding of the choice of the additive and the amount of additive needed to deliver a metastable polymorph or amorphous structure is desired (Eloy and Marchetti, 2013).  Additionally, many compounds which are formulated as amorphous dispersions are larger molecules which have a naturally low tendency to form crystals.  Previous work has shown that the formation of metastable structures is enhanced by utilizing a monodisperse droplet evaporation technique (Carver and Snyder, 2012).

In this presentation, we highlight our recent work on the formation of metastable polymorphs and amorphous structures of a molecule with a high propensity to crystallize, succinic acid.  The structures are generated through monodispersed droplet evaporation using a vibrating orifice aerosol generator, with solution addition of polymer excipient.   Succinic acid has two known polymorphs, with a significant tendency to form only the beta structure at room temperature.  Furthermore, succinic acid has a very high propensity to crystallize, which is characteristically different from many substances that are formed into an amorphous state.  We will show that polyvinylpyrrolidone (PVP) is a compatible excipient for the creation of amorphous dispersions of succinic acid in multiple solvents.  In ethanol, the metastable alpha polymorph of succinic acid is formed at low loadings of PVP.  At higher loadings, we will show the fraction of PVP required to obtain a purely amorphous sample, as a function of the solvent used and the PVP molecular weight.  Additionally, a theory will be presented to explain the PVP fraction required for amorphous dispersion formation with succinic acid.  Finally, we will discuss both the morphological impact of PVP addition on succinic acid morphology as well as the potential of this work to extend to more general methods to predict the formation of amorphous structures.


Bernstein, J. Polymorphism in Molecular Crystals; Oxford, New York, 2002.

Carver, K. M., Snyder, R. C. Ind. Eng. Chem. Res. 2012, 51, 15720-15728.

Eloy, J. O., Marchetti, J. M. Powder Technology. 2013, 253, 98-106

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