title: Hot-melt extrusion of polyvinyl alcohol for oral immediate release applications.
abstract: The primary purpose of this study was to process partially hydrolyzed PVOH grades (degree of hydroxylation (DH): 33-88%) via HME and to evaluate them as carrier for oral immediate release dosage forms in order to improve the release rate of poorly water soluble drugs (i.e., HCT and CEL) via the formulation of solid dispersions. PVOH grades (DH >70%) were able to solubilize HCT and CEL up to 15%, but required higher extrusion temperature, due to the crystalline nature of PVOH. The highest drug release rate was observed from hot-melt extruded PVOH samples with a high DH. While drug release from extrudates consisting of PVOH with a low DH was affected by ionic strength, there was no influence of pH and ionic strength on HCT release from PVOH samples with a higher DH. However, PVOH (DH >70%) required higher extrusion temperatures, which could hamper its application for thermosensitive drugs. Therefore, the secondary purpose was to investigate the effect of sorbitol, a water-soluble plasticizer, on the thermal properties of hot-melt extruded PVOH (DH >70%). The melting of PVOH/sorbitol mixture was required to establish molecular interactions between PVOH and sorbitol. These molecular interactions were reflected in the HME behavior: whereas an extrusion temperature of 180 °C was necessary to process physical mixtures of PVOH (DH >70%) and sorbitol, only 140 °C was necessary during re-extrusion (after quench cooling and cryomilling) of the PVOH/sorbitol mixture. In addition, the in vitro and in vivo dug release of plasticized PVOH was examined; whereas the CEL/PVO/sorbitol system was able to maintain supersaturation during in vitro dissolution (0.1N HCl) compared to Celebrex(®), the in vivo pharmacokinetic parameters (AUC0-24h, Cmax and Tmax) were highly comparable.
authors.affiliation: Laboratory of Pharmaceutical Technology, Ghent University, Ghent, Belgium.
authors.forename: W
authors.initials: W
authors.lastname: De Jaeghere
authors.affiliation: Laboratory of Pharmaceutical Process Analytical Technology, Ghent University, Ghent, Belgium.
authors.forename: T
authors.initials: T
authors.lastname: De Beer
authors.affiliation: Laboratory of Medical Biochemistry and Clinical Analysis, Ghent University, Ghent, Belgium.
authors.forename: J
authors.initials: J
authors.lastname: Van Bocxlaer
authors.affiliation: Laboratory of Pharmaceutical Technology, Ghent University, Ghent, Belgium.
authors.forename: J P
authors.initials: JP
authors.lastname: Remon
authors.affiliation: Laboratory of Pharmaceutical Technology, Ghent University, Ghent, Belgium. Electronic address: Chris.Vervaet@UGent.be.
authors.forename: C
authors.initials: C
authors.lastname: Vervaet
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D000068579:Celecoxib / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D004285:Dogs; D004337:Drug Carriers / Q000737:chemistry* / Q000493:pharmacokinetics; D004339:Drug Compounding; D065546:Drug Liberation; D006358:Hot Temperature; D006852:Hydrochlorothiazide / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D009994:Osmolar Concentration; D011142:Polyvinyl Alcohol / Q000737:chemistry* / Q000493:pharmacokinetics
chemical_list: D004337:Drug Carriers; D006852:Hydrochlorothiazide; D011142:Polyvinyl Alcohol; D000068579:Celecoxib
keywords: Hot-melt extrusion; Immediate release; Oral drug delivery; Polyvinyl alcohol; Supersaturation