title: Enabling thermal processing of ritonavir-polyvinyl alcohol amorphous solid dispersions by KinetiSol® Dispersing.
abstract: Polyvinyl alcohol has received little attention as a matrix polymer in amorphous solid dispersions (ASDs) due to its thermal and rheological limitations in extrusion processing and limited organic solubility in spray drying applications. Additionally, in extrusion processing, the high temperatures required to process often exclude thermally labile APIs. The purpose of this study was to evaluate the feasibility of processing polyvinyl alcohol amorphous solid dispersions utilizing the model compound ritonavir with KinetiSol® Dispersing (KSD) technology. The effects of KSD rotor speed and ejection temperature on the physicochemical properties of the processed material were evaluated. Powder X-ray diffraction and modulated differential scanning calorimetry were used to confirm amorphous conversion. Liquid chromatography-mass spectroscopy was used to characterize and identify degradation pathways of ritonavir during KSD processing and (13)C nuclear magnetic resonance spectroscopy was used to investigate polymer stability. An optimal range of processing conditions was found that resulted in amorphous product and minimal to no drug and polymer degradation. Drug release of the ASD produced from the optimal processing conditions was evaluated using a non-sink, pH-shift dissolution test. The ability to process amorphous solid dispersions with polyvinyl alcohol as a matrix polymer will enable further investigations of the polymer's performance in amorphous systems for poorly water-soluble compounds.
authors: College of Pharmacy, The University of Texas at Austin, 2409 University Avenue, A1920, Austin, TX 78712, USA. Electronic address: justin.lafountaine@utexas.edu.
authors: Justin S
authors: JS
authors: LaFountaine
authors: College of Pharmacy, The University of Texas at Austin, 2409 University Avenue, A1920, Austin, TX 78712, USA.
authors: Scott V
authors: SV
authors: Jermain
authors: College of Pharmacy, The University of Texas at Austin, 2409 University Avenue, A1920, Austin, TX 78712, USA.
authors: Leena Kumari
authors: LK
authors: Prasad
authors: DisperSol Technologies, LLC, 111 Cooperative Way, Georgetown, TX 78626, USA.
authors: Chris
authors: C
authors: Brough
authors: DisperSol Technologies, LLC, 111 Cooperative Way, Georgetown, TX 78626, USA.
authors: Dave A
authors: DA
authors: Miller
authors: Merck KGaA, Frankfurter Str. 250, D 64293 Darmstadt, Germany.
authors: Dieter
authors: D
authors: Lubda
authors: College of Pharmacy, The University of Texas at Austin, 2409 University Avenue, A1920, Austin, TX 78712, USA.
authors: James W
authors: JW
authors: McGinity
authors: College of Pharmacy, The University of Texas at Austin, 2409 University Avenue, A1920, Austin, TX 78712, USA.
authors: Robert O
authors: RO
authors: Williams
mesh_terms: D002152:Calorimetry, Differential Scanning / Q000379:methods; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003890:Desiccation; D004337:Drug Carriers / Q000737:chemistry; D004339:Drug Compounding / Q000379:methods*; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry; D006358:Hot Temperature; D011108:Polymers / Q000737:chemistry; D011142:Polyvinyl Alcohol / Q000737:chemistry*; D019438:Ritonavir / Q000737:chemistry*; D012995:Solubility; D013696:Temperature; D014867:Water / Q000737:chemistry; D014961:X-Ray Diffraction / Q000379:methods
chemical_list: D004337:Drug Carriers; D005079:Excipients; D011108:Polymers; D014867:Water; D011142:Polyvinyl Alcohol; D019438:Ritonavir
keywords: KinetiSol Dispersing; Polymer degradation; Polyvinyl alcohol; Ritonavir; Thermal processing