title: Use of Polyvinyl Alcohol as a Solubility-Enhancing Polymer for Poorly Water Soluble Drug Delivery (Part 1).
abstract: Polyvinyl alcohol (PVAL) has not been investigated in a binary formulation as a concentration-enhancing polymer owing to its high melting point/high viscosity and poor organic solubility. Due to the unique attributes of the KinetiSol® dispersing (KSD) technology, PVAL has been enabled for this application and it is the aim of this paper to investigate various grades for improvement of the solubility and bioavailability of poorly water soluble active pharmaceutical ingredients. Solid amorphous dispersions were created with the model drug, itraconazole (ITZ), at a selected drug loading of 20%. Polymer grades were chosen with variation in molecular weight and degree of hydroxylation to determine the effects on performance. Differential scanning calorimetry, powder X-ray diffraction, polarized light microscopy, size exclusion chromatography, and dissolution testing were used to characterize the amorphous dispersions. An in vivo pharmacokinetic study in rats was also conducted to compare the selected formulation to current market formulations of ITZ. The 4-88 grade of PVAL was determined to be effective at enhancing solubility and bioavailability of itraconazole.
authors.affiliation: Division of Pharmaceutics, College of Pharmacy, The University of Texas at Austin, 1 University Station, Campus Mail Code A1902, Austin, Texas, 78712, USA. chris.brough@dispersoltech.com.|DisperSol Technologies, LLC, 111 W. Cooperative Way, Building 3, Georgetown, Texas, 78626, USA. chris.brough@dispersoltech.com.
authors.forename: Chris
authors.initials: C
authors.lastname: Brough
authors.affiliation: DisperSol Technologies, LLC, 111 W. Cooperative Way, Building 3, Georgetown, Texas, 78626, USA.
authors.forename: Dave A
authors.initials: DA
authors.lastname: Miller
authors.affiliation: DisperSol Technologies, LLC, 111 W. Cooperative Way, Building 3, Georgetown, Texas, 78626, USA.
authors.forename: Justin M
authors.initials: JM
authors.lastname: Keen
authors.affiliation: Merck KGaA, Frankfurter Str. 250, 64293, Darmstadt, Germany.
authors.forename: Shawn A
authors.initials: SA
authors.lastname: Kucera
authors.affiliation: Merck KGaA, Frankfurter Str. 250, 64293, Darmstadt, Germany.
authors.forename: Dieter
authors.initials: D
authors.lastname: Lubda
authors.affiliation: Division of Pharmaceutics, College of Pharmacy, The University of Texas at Austin, 1 University Station, Campus Mail Code A1902, Austin, Texas, 78712, USA.
authors.forename: Robert O
authors.initials: RO
authors.lastname: Williams
mesh_terms: D000818:Animals; D001682:Biological Availability; D002152:Calorimetry, Differential Scanning / Q000379:methods; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004339:Drug Compounding / Q000379:methods; D016503:Drug Delivery Systems / Q000379:methods; D005079:Excipients / Q000737:chemistry; D017964:Itraconazole / Q000737:chemistry* / Q000493:pharmacokinetics; D008297:Male; D011108:Polymers / Q000737:chemistry*; D011142:Polyvinyl Alcohol / Q000737:chemistry*; D011208:Powders / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D014867:Water / Q000737:chemistry*; D014961:X-Ray Diffraction / Q000379:methods
chemical_list: D005079:Excipients; D011108:Polymers; D011208:Powders; D014867:Water; D017964:Itraconazole; D011142:Polyvinyl Alcohol
keywords: KinetiSol® dispersing; PVAL 4-88; itraconazole; polyvinyl alcohol; solid amorphous dispersions