title: Mechanistic insights into the dissolution of spray-dried amorphous solid dispersions.
abstract: We have investigated the dissolution mechanisms of spray-dried amorphous solid dispersions of the poorly water-soluble drug felodipine and the water-soluble polymer copovidone using a new combined spectrophotometric and magnetic resonance imaging technique and a mathematical modelling approach. Studies of the dissolution rates of both uncompacted and compacted solid dispersions revealed that compaction leads to a significant decrease in the rate and extent of dissolution and a strong dependence on drug loading, especially for the uncompacted samples. Low drug-loaded compacts [5% and 15% (w/w) felodipine] eroded with linear kinetics at identical rates, pointing to matrix control, whereas for compacts containing a higher proportion of felodipine (≥ 30%, w/w), dissolution performance was dominated by the drug. In these cases, felodipine concentrations were extremely low and the compact swelled rather than eroded. We have developed a mathematical population balance framework to model the processes of particle release, dissolution and crystal growth. This was found to accurately describe the bell-shaped dissolution profiles observed for the compacts containing a low felodipine loading.
authors.affiliation: School of Pharmacy, University of Nottingham, Nottingham NG7 2RD, United Kingdom.
authors.forename: Zoe A
authors.initials: ZA
authors.lastname: Langham
authors.forename: Jonathan
authors.initials: J
authors.lastname: Booth
authors.forename: Les P
authors.initials: LP
authors.lastname: Hughes
authors.forename: Gavin K
authors.initials: GK
authors.lastname: Reynolds
authors.forename: Stephen A C
authors.initials: SA
authors.lastname: Wren
mesh_terms: D000889:Anti-Arrhythmia Agents / Q000737:chemistry*; D003460:Crystallization; D003890:Desiccation; D004867:Equipment Design; D015736:Felodipine / Q000737:chemistry*; D008279:Magnetic Resonance Imaging / Q000295:instrumentation*; D008956:Models, Chemical; D033362:Powder Diffraction; D011759:Pyrrolidines / Q000737:chemistry*; D012995:Solubility; D013053:Spectrophotometry / Q000295:instrumentation*; D014753:Vinyl Compounds / Q000737:chemistry*; D014961:X-Ray Diffraction
chemical_list: D000889:Anti-Arrhythmia Agents; D011759:Pyrrolidines; D014753:Vinyl Compounds; C402301:poly(vinylpyrrolidone-co-vinyl-acetate); D015736:Felodipine