title: Microfibrous Solid Dispersions of Poorly Water-Soluble Drugs Produced via Centrifugal Spinning: Unexpected Dissolution Behavior on Recrystallization.
abstract: Temperature-controlled, solvent-free centrifugal spinning may be used as a means of rapid production of amorphous solid dispersions in the form of drug-loaded sucrose microfibers. However, due to the high content of amorphous sucrose in the formulations, such microfibers may be highly hygroscopic and unstable on storage. In this study, we explore both the effects of water uptake of the microfibers and the consequences of deliberate recrystallization for the associated dissolution profiles. The stability of sucrose microfibers loaded with three selected BCS class II model drugs (itraconazole (ITZ), olanzapine (OLZ), and piroxicam (PRX)) was investigated under four different relative humidity conditions (11, 33, 53, and 75% RH) at 25 °C for 8 months, particularly focusing on the effect of the highest level of moisture (75% RH) on the morphology, size, drug distribution, physical state, and dissolution performance of microfibers. While all samples were stable at 11% RH, at 33% RH the ITZ-sucrose system showed greater resistance against devitrification compared to the OLZ- and PRX-sucrose systems. For all three samples, the freshly prepared microfibers showed enhanced dissolution and supersaturation compared to the drug alone and physical mixes; surprisingly, the dissolution advantage was largely maintained or even enhanced (in the case of ITZ) following the moisture-induced recrystallization under 75% RH. Therefore, this study suggests that the moisture-induced recrystallization process may result in considerable dissolution enhancement compared to the drug alone, while overcoming the physical stability risks associated with the amorphous state.
authors.affiliation: School of Pharmacy, University College London , 29-39 Brunswick Square, London, WC1N 1AX, U.K.
authors.forename: Stefania
authors.initials: S
authors.lastname: Marano
authors.affiliation: School of Pharmacy, University College London , 29-39 Brunswick Square, London, WC1N 1AX, U.K.
authors.forename: Susan A
authors.identifier: 0000-0003-4880-0253
authors.initials: SA
authors.lastname: Barker
authors.affiliation: School of Pharmacy, University College London , 29-39 Brunswick Square, London, WC1N 1AX, U.K.
authors.forename: Bahijja T
authors.initials: BT
authors.lastname: Raimi-Abraham
authors.affiliation: Colorcon Inc. , Global Headquarters, 275 Ruth Road, Harleysville, Pennsylvania 19438, United States.
authors.forename: Shahrzad
authors.initials: S
authors.lastname: Missaghi
authors.affiliation: Colorcon Inc. , Global Headquarters, 275 Ruth Road, Harleysville, Pennsylvania 19438, United States.
authors.forename: Ali
authors.initials: A
authors.lastname: Rajabi-Siahboomi
authors.affiliation: Department of Chemistry, University College London , 20 Gordon Street, London, WC1H 0AJ, U.K.
authors.forename: Abil E
authors.initials: AE
authors.lastname: Aliev
authors.affiliation: School of Pharmacy, University College London , 29-39 Brunswick Square, London, WC1N 1AX, U.K.
authors.forename: Duncan Q M
authors.identifier: 0000-0003-1294-8993
authors.initials: DQM
authors.lastname: Craig
mesh_terms: D001569:Benzodiazepines / Q000737:chemistry; D003460:Crystallization / Q000379:methods*; D004355:Drug Stability; D017964:Itraconazole / Q000737:chemistry; D000077152:Olanzapine; D010894:Piroxicam / Q000737:chemistry; D012995:Solubility; D013395:Sucrose / Q000737:chemistry; D014867:Water / Q000737:chemistry*
chemical_list: D014867:Water; D001569:Benzodiazepines; D010894:Piroxicam; D017964:Itraconazole; D013395:Sucrose; D000077152:Olanzapine
keywords: amorphous; centrifugal spinning; crystallization; microfiber; poorly water-soluble drug; solid dispersion; stability; sucrose; supersaturation