title: Stability-enhanced hot-melt extruded amorphous solid dispersions via combinations of Soluplus® and HPMCAS-HF.
abstract: The aim of this study was to evaluate a novel combination of Soluplus® and hypromellose acetate succinate (HPMCAS-HF) polymers for solubility enhancement as well as enhanced physicochemical stability of the produced amorphous solid dispersions. This was accomplished by converting the poorly water-soluble crystalline form of carbamazepine into a more soluble amorphous form within the polymeric blends. Carbamazepine (CBZ), a Biopharmaceutics Classification System class II active pharmaceutical ingredient (API) with multiple polymorphs, was utilized as a model drug. Hot-melt extrusion (HME) processing was used to prepare solid dispersions utilizing blends of polymers. Drug loading showed a significant effect on the dissolution rate of CBZ in all of the tested ratios of Soluplus® and HPMCAS-HF. CBZ was completely miscible in the polymeric blends of Soluplus® and HPMCAS-HF up to 40% drug loading. The extrudates were characterized by differential scanning calorimetry (DSC), X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy and dissolution studies. DSC and XRD data confirmed the formation of amorphous solid dispersions of CBZ in the polymeric blends of Soluplus® and HPMCAS-HF. Drug loading and release of CBZ was increased with Soluplus® (when used as the primary matrix polymer) when formulations contained Soluplus® with 7-21% (w/w) HPMCAS-HF. In addition, this blend of polymers was found to be physically and chemically stable at 40°C, 75% RH over 12 months without any dissolution rate changes.
authors.affiliation: Department of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, University, Mississippi, 38677, USA.
authors.forename: Saad M
authors.initials: SM
authors.lastname: Alshahrani
authors.forename: Wenli
authors.initials: W
authors.lastname: Lu
authors.forename: Jun-Bom
authors.initials: JB
authors.lastname: Park
authors.forename: Joseph T
authors.initials: JT
authors.lastname: Morott
authors.forename: Bader B
authors.initials: BB
authors.lastname: Alsulays
authors.forename: Soumyajit
authors.initials: S
authors.lastname: Majumdar
authors.forename: Nigel
authors.initials: N
authors.lastname: Langley
authors.forename: Karl
authors.initials: K
authors.lastname: Kolter
authors.forename: Andreas
authors.initials: A
authors.lastname: Gryczke
authors.forename: Michael A
authors.initials: MA
authors.lastname: Repka
mesh_terms: D002152:Calorimetry, Differential Scanning; D002220:Carbamazepine / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D006358:Hot Temperature; D008747:Methylcellulose / Q000031:analogs & derivatives* / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry*; D011145:Polyvinyls / Q000737:chemistry*; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D013818:Thermogravimetry; D014961:X-Ray Diffraction
chemical_list: D011145:Polyvinyls; C572167:polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer; D002220:Carbamazepine; D011092:Polyethylene Glycols; C048331:hydroxypropylmethylcellulose acetate succinate; D008747:Methylcellulose