Development of fully amorphous dispersions of a low Tg drug via co-spray drying with hydrophilic polymers

The aim of the study was to prepare molecular dispersions of a physically highly unstable amorphous drug, paracetamol (acetaminophen with a Tg of ca. 25 °C) via co-spray drying with a variety of polymers. Solid dispersions at a range of drug loadings (10–90%w/w) using hydroxypropyl methylcellulose/acetate succinate (HPMC/HPMC AS), polyvinylpyrrolidone (PVP) and copovidone were produced and characterised by modulated temperature differential scanning calorimetry (MTDSC), thermogravimetric analysis (TGA), X-ray powder diffraction (XRPD), Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). PVP-based polymers showed a greater tendency than the HPMC-based group to generate temperature-stable dispersions. In particular, copovidone (Plasdone® S-630) was found to be the most effective of the polymers studied and could formulate molecular dispersions at drug loadings up to and including 40%w/w. However, no evidence for direct drug–polymer interactions was found for such systems as a possible stabilising mechanism. The expected relationship of a higher Tg of the polymer leading to greater stabilisation was not observed, while there was an inverse relationship between viscosity grade and amorphous phase generation. The study has therefore shown that temperature-stable amorphous dispersions of a low Tg drug may be prepared by co-spray drying, particularly using PVP-based polymers.

Co-spray drying a low Tg drug (paracetamol) with polyvinylpyrrolidone and HPMC-based polymers leads to the production of particles, depending on the loading and choice of polymer. The relationship between the formulation and subsequent production of fully amorphous particles is explored and discussed.Figure optionsDownload high-quality image (59 K)Download as PowerPoint slide