Functionalized Silica Nanoparticles as Additives for
Polymorphic Control in Emulsion-Based Crystallization of Glycine
- Publication date
- Publisher
Abstract
Emulsion-based crystallization to produce spherical crystalline
agglomerates is an attractive route to control the size and morphology
of active pharmaceutical ingredient (API) crystals, which in turn
improves downstream processability. Here, we demonstrate the use of
silica nanoparticles modified with different surface functional groups
(hydroxyl, amino, carboxylic, imidazolim chloride, and chloride) as
additives in water-in-oil emulsion-based crystallization of glycine,
a model API molecule. Spherical agglomerates of glycine obtained under
different experimental conditions are characterized by powder X-ray
diffraction (XRD) and scanning electron microscopy. Our observations
reveal the strong influence of particle functionalization on polymorphic
outcome at near-neutral (pH ∼6) conditions, where we are able
to selectively crystallize the least stable β-polymorph of glycine
or tune the relative ratio of α- and β-polymorphs by selecting
appropriate experimental conditions. Mixtures of α- and γ-glycine
are typically obtained under acidic solutions (pH ∼3), irrespective
of the functional groups used. We examine the influence of charge
and immobilization density of surface functional groups and nanoparticle
concentration on the polymorphic outcome and rationalize our results
by analyzing molecular and functional group speciation