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

作者：Zhao Min; Barker Susan A; Belton Peter S; McGregor Caroline; Craig Duncan Q M^*

来源：European Journal of Pharmaceutics and Biopharmaceutics, 2012, 82(3): 572-579.

DOI：10.1016/j.ejpb.2012.07.012

• Amorphous
• Acetaminophen
• Paracetamol
• Pyrrolidone
• Solid dispersion
• Spray drying

The aim of the study was to prepare molecular dispersions of a physically highly unstable amorphous drug, paracetamol (acetaminophen with a T-g of ca. 25 degrees 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 (FIR) 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 (R) 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 T-g 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 T-g drug may be prepared by co-spray drying, particularly using PVP-based polymers.

• 出版日期2012-11