Mid-infrared spectroscopy as a polymer selection tool for formulating amorphous solid dispersions.

OBJECTIVES

The development of amorphous solid dispersions is of increasing interest in the delivery of bioactive compounds; however, there is a need for a methodology that enables the rational selection of polymers for solid dispersion formulations with optimal stability to crystallization. The objective of this study was to evaluate the use of mid-infrared (IR) spectroscopy for this purpose.

METHODS

Polymers evaluated included poly(vinylpyrrolidone) (PVP), Eudragit E100 (E100), carboxymethylcellulose acetate butyrate (CMCAB), hydroxypropylmethylcellulose (HPMC), HPMC acetate succinate (HPMCAS) and poly(acrylic acid) (PAA). Model crystalline bioactive polyphenols included quercetin and naringenin. Amorphous solid dispersions were prepared by dissolving both polyphenol and polymer in a common solvent followed by solvent evaporation. Mid-IR spectroscopy was used to determine and quantify the extent of polyphenol-polymer interactions, and powder X-ray diffraction was used to monitor physical stability following storage at different environmental conditions.

KEY FINDINGS

The mid-IR analysis suggested the following rank order for the crystallization-inhibiting performance of the different polymers: E100 > PVP > HPMCAS > HPMC ≥ CMCAB > PAA. The initial performance of the different polymers was evaluated using the highest concentration of polyphenol for which x-ray amorphous solid dispersions could be prepared via rotary evaporation. The observed stability followed that predicted from the mid-infrared spectroscopy evaluation of intermolecular interactions. The dispersions with better polyphenol-polymer interactions were stable against crystallization when exposed to high relative humidity and high temperatures; on the other hand, systems that had weak interactions were not stable to crystallization when stored at moderate environmental conditions.

CONCLUSIONS

Based on the observed ability of mid-IR analysis to enable the characterization of intermolecular polyphenol-polymer interactions and based on the correlation between the extent of intermolecular interactions and the crystallization-inhibiting performance of polymers, it can be concluded that this technique is an important tool for the rational formulation of solid dispersions with optimized physical stability.