Effects of some polymeric additives on the cocrystallization of naproxen and nicotinamide via freeze drying

Abstract

Crystallization of active pharmaceutical ingredients (APIs) has important implications for their bioavailability. Their dissolution behavior is affected by the phase, size, and dispersion of the crystal particles. Polymeric additives have served as effective modifiers of the API crystallization, and we tested their effects during the crystallization via freeze drying. Poly(vinylpyrrolidone), poly(vinylpyrrolidone-co-vinyl acetate), and poly(acrylic acid) were investigated for their effects on the cocrystallization of naproxen (API) and nicotinamide (coformer). We aimed to establish the types and concentrations of the polymers that modulated the size and dispersion of the particles without affecting the cocrystal phase. Poly(vinylpyrrolidone) (Mw 40000) and poly(vinylpyrrolidone-co-vinyl acetate) (Mw 45000–70000) at the concentration level of 3–5% were effective in this regard in increasing the initial and overall API dissolution, which was correlated with the microstructure of the freeze-dried solids. This study is intended to contribute to foundations for further research to apply crystal-modulating additives to the process of freeze drying.