title: Development of fully amorphous dispersions of a low T(g) drug via co-spray drying with hydrophilic polymers.
abstract: 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°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 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.
authors.affiliation: School of Pharmacy, University of East Anglia, Norwich, UK.
authors.forename: Min
authors.initials: M
authors.lastname: Zhao
authors.forename: Susan A
authors.initials: SA
authors.lastname: Barker
authors.forename: Peter S
authors.initials: PS
authors.lastname: Belton
authors.forename: Caroline
authors.initials: C
authors.lastname: McGregor
authors.forename: Duncan Q M
authors.initials: DQ
authors.lastname: Craig
mesh_terms: D000082:Acetaminophen / Q000008:administration & dosage* / Q000737:chemistry; D002152:Calorimetry, Differential Scanning; D004337:Drug Carriers / Q000737:chemistry*; D004355:Drug Stability; D065347:Hypromellose Derivatives; D008747:Methylcellulose / Q000031:analogs & derivatives / Q000737:chemistry; D008855:Microscopy, Electron, Scanning; D011108:Polymers / Q000737:chemistry*; D011205:Povidone / Q000737:chemistry; D011759:Pyrrolidines; D017550:Spectroscopy, Fourier Transform Infrared; D013696:Temperature; D013818:Thermogravimetry; D044366:Transition Temperature; D014753:Vinyl Compounds; D014783:Viscosity; D014961:X-Ray Diffraction
chemical_list: D004337:Drug Carriers; D011108:Polymers; D011759:Pyrrolidines; D014753:Vinyl Compounds; C402301:poly(vinylpyrrolidone-co-vinyl-acetate); D000082:Acetaminophen; D065347:Hypromellose Derivatives; C048331:hydroxypropylmethylcellulose acetate succinate; D008747:Methylcellulose; D011205:Povidone