title: Use of Polyvinyl Alcohol as a Solubility Enhancing Polymer for Poorly Water-Soluble Drug Delivery (Part 2).
abstract: The KinetiSol® Dispersing (KSD) technology has enabled the investigation into the use of polyvinyl alcohol (PVAL) as a concentration enhancing polymer for amorphous solid dispersions. Our previous study revealed that the 88% hydrolyzed grade of PVAL was optimal for itraconazole (ITZ) amorphous compositions with regard to solid-state properties, non-sink dissolution performance, and bioavailability enhancement. The current study investigates the influence of molecular weight for the 88% hydrolyzed grades of PVAL on the properties of KSD processed ITZ:PVAL amorphous dispersions. Specifically, molecular weights in the processable range of 4 to 18 mPa · s were evaluated and the 4-88 grade provided the highest AUC dissolution profile. Amorphous dispersions at 10, 20, 30, 40, and 50% ITZ drug loads in PVAL 4-88 were also compared by dissolution performance. Analytical tools of diffusion-ordered spectroscopy and Fourier transform infrared spectroscopy were employed to understand the interaction between drug and polymer. Finally, results from a 30-month stability test of a 30% drug loaded ITZ:PVAL 4-88 composition shows that stable amorphous dispersions can be achieved. Thus, this newly enabled polymer carrier can be considered a viable option for pharmaceutical formulation development for solubility enhancement.
authors: 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: Chris
authors: C
authors: Brough
authors: DisperSol Technologies, LLC, 111 W. Cooperative Way, Building 3, Georgetown, Texas, 78626, USA.
authors: Dave A
authors: DA
authors: Miller
authors: Division of Pharmaceutics, College of Pharmacy, The University of Texas at Austin, 1 University Station, Campus Mail Code A1902, Austin, Texas, 78712, USA.|DisperSol Technologies, LLC, 111 W. Cooperative Way, Building 3, Georgetown, Texas, 78626, USA.
authors: Daniel
authors: D
authors: Ellenberger
authors: Merck KGaA, Frankfurter Str. 250, D 64293, Darmstadt, Germany.
authors: Dieter
authors: D
authors: Lubda
authors: Division of Pharmaceutics, College of Pharmacy, The University of Texas at Austin, 1 University Station, Campus Mail Code A1902, Austin, Texas, 78712, USA.
authors: Robert O
authors: RO
authors: Williams
mesh_terms: D001682:Biological Availability; 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; D011108:Polymers / Q000737:chemistry*; D011142:Polyvinyl Alcohol / Q000737:chemistry*; D012995:Solubility; D014867:Water / Q000737:chemistry*
chemical_list: D005079:Excipients; D011108:Polymers; D014867:Water; D017964:Itraconazole; D011142:Polyvinyl Alcohol
keywords: PVAL; amorphous solid dispersion; itraconazole; polyvinyl alcohol; solubility enhancement