title: Investigating the Dissolution Performance of Amorphous Solid Dispersions Using Magnetic Resonance Imaging and Proton NMR.
abstract: We have investigated the dissolution performance of amorphous solid dispersions of poorly water-soluble bicalutamide in a Kollidon VA64 polymeric matrix as a function of the drug loading (5% vs. 30% bicalutamide). A combined suite of state-of-the-art analytical techniques were employed to obtain a clear picture of the drug release, including an integrated magnetic resonance imaging UV-Vis flow cell system and 1H-NMR. Off-line 1H-NMR was used for the first time to simultaneously measure the dissolution profiles and rates of both the drug and the polymer from a solid dispersion. MRI and 1H-NMR data showed that the 5% drug loading compact erodes linearly, and that bicalutamide and Kollidon VA64 are released at approximately the same rate from the molecular dispersion. For the 30% extrudate, data indicated a slower water ingress into the compact which corresponds to a slower dissolution rate of both bicalutamide and Kollidon VA64.
authors.affiliation: School of Pharmacy, Boots Science Building, University of Nottingham, Nottingham NG7 2RD, UK. francesco.tres@nottingham.ac.uk.
authors.forename: Francesco
authors.initials: F
authors.lastname: Tres
authors.affiliation: Pharmaceutical Development, AstraZeneca, Macclesfield SK10 2NA, UK. Steven.Coombes@astrazeneca.com.
authors.forename: Steven R
authors.initials: SR
authors.lastname: Coombes
authors.affiliation: Pharmaceutical Development, AstraZeneca, Macclesfield SK10 2NA, UK. andrew.r.phillips@astrazeneca.com.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Phillips
authors.affiliation: Pharmaceutical Development, AstraZeneca, Macclesfield SK10 2NA, UK. Les.Hughes2@astrazeneca.com.
authors.forename: Leslie P
authors.initials: LP
authors.lastname: Hughes
authors.affiliation: Pharmaceutical Development, AstraZeneca, Macclesfield SK10 2NA, UK. Stephen.Wren@astrazeneca.com.
authors.forename: Stephen A C
authors.initials: SA
authors.lastname: Wren
authors.affiliation: School of Pharmacy, Boots Science Building, University of Nottingham, Nottingham NG7 2RD, UK. Jon.Aylott@nottingham.ac.uk.
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Aylott
authors.affiliation: School of Pharmacy, Boots Science Building, University of Nottingham, Nottingham NG7 2RD, UK. jonathan.burley@nottingham.ac.uk.
authors.forename: Jonathan C
authors.initials: JC
authors.lastname: Burley
mesh_terms: D000813:Anilides / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D004339:Drug Compounding; D065546:Drug Liberation; D004355:Drug Stability; D008279:Magnetic Resonance Imaging / Q000379:methods*; D009570:Nitriles / Q000737:chemistry; D066244:Proton Magnetic Resonance Spectroscopy / Q000379:methods*; D014105:Tosyl Compounds / Q000737:chemistry
chemical_list: D000813:Anilides; D009570:Nitriles; D014105:Tosyl Compounds; C053541:bicalutamide
keywords: amorphous solid dispersions; bicalutamide; hot melt extrusion; magnetic resonance imaging; poorly soluble drugs; solid-state transformations; suppressed water 1H-NMR