title: Thermal Processing of PVP- and HPMC-Based Amorphous Solid Dispersions.
abstract: Thermal processing technologies continue to gain interest in pharmaceutical manufacturing. However, the types and grades of polymers that can be utilized in common thermal processing technologies, such as hot-melt extrusion (HME), are often limited by thermal or rheological factors. The objectives of the present study were to compare and contrast two thermal processing methods, HME and KinetiSol® Dispersing (KSD), and investigate the influence of polymer type, polymer molecular weight, and drug loading on the ability to produce amorphous solid dispersions (ASDs) containing the model compound griseofulvin (GRIS). Dispersions were analyzed by a variety of imaging, solid-state, thermal, and solution-state techniques. Dispersions were prepared by both HME and KSD using polyvinylpyrrolidone (PVP) K17 or hydroxypropyl methylcellulose (HPMC) E5. Dispersions were only prepared by KSD using higher molecular weight grades of HPMC and PVP, as these could not be extruded under the conditions selected. Powder X-ray diffraction (PXRD) analysis showed that dispersions prepared by HME were amorphous at 10% and 20% drug load; however, it showed significant crystallinity at 40% drug load. PXRD analysis of KSD samples showed all formulations and drug loads to be amorphous with the exception of trace crystallinity seen in PVP K17 and PVP K30 samples at 40% drug load. These results were further supported by other analytical techniques. KSD produced amorphous dispersions at higher drug loads than could be prepared by HME, as well as with higher molecular weight polymers that were not processable by HME, due to its higher rate of shear and torque output.
authors.affiliation: Division of Pharmaceutics, College of Pharmacy, The University of Texas at Austin, 2409 University Avenue, A1920, Austin, Texas, 78712, USA. justin.lafountaine@utexas.edu.
authors.forename: Justin S
authors.initials: JS
authors.lastname: LaFountaine
authors.affiliation: Division of Pharmaceutics, College of Pharmacy, The University of Texas at Austin, 2409 University Avenue, A1920, Austin, Texas, 78712, USA.
authors.forename: Leena Kumari
authors.initials: LK
authors.lastname: Prasad
authors.affiliation: Division of Pharmaceutics, College of Pharmacy, The University of Texas at Austin, 2409 University Avenue, A1920, Austin, Texas, 78712, USA.|DisperSol Technologies, LLC, 111 Cooperative Way, Georgetown, Texas, 78626, USA.
authors.forename: Chris
authors.initials: C
authors.lastname: Brough
authors.affiliation: DisperSol Technologies, LLC, 111 Cooperative Way, Georgetown, Texas, 78626, USA.
authors.forename: Dave A
authors.initials: DA
authors.lastname: Miller
authors.affiliation: Division of Pharmaceutics, College of Pharmacy, The University of Texas at Austin, 2409 University Avenue, A1920, Austin, Texas, 78712, USA.
authors.forename: James W
authors.initials: JW
authors.lastname: McGinity
authors.affiliation: Division of Pharmaceutics, College of Pharmacy, The University of Texas at Austin, 2409 University Avenue, A1920, Austin, Texas, 78712, USA.
authors.forename: Robert O
authors.initials: RO
authors.lastname: Williams
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods; D004337:Drug Carriers / Q000737:chemistry; D004339:Drug Compounding / Q000379:methods*; D005079:Excipients / Q000737:chemistry; D006118:Griseofulvin / Q000737:chemistry; D006358:Hot Temperature; D007785:Lactose / Q000031:analogs & derivatives* / Q000737:chemistry; D008747:Methylcellulose / Q000031:analogs & derivatives* / Q000737:chemistry; D008970:Molecular Weight; D011108:Polymers / Q000737:chemistry*; D011145:Polyvinyls / Q000737:chemistry*; D011759:Pyrrolidines / Q000737:chemistry*; D012996:Solutions / Q000737:chemistry; D014961:X-Ray Diffraction / Q000379:methods
chemical_list: D004337:Drug Carriers; D005079:Excipients; D011108:Polymers; D011145:Polyvinyls; D011759:Pyrrolidines; D012996:Solutions; C509290:hydroxypropylmethylcellulose-lactose matrix; C505150:poly(N-vinylpyrrolidine); D006118:Griseofulvin; D008747:Methylcellulose; D007785:Lactose
keywords: KinetiSol® Dispersing; griseofulvin; hot-melt extrusion; hydroxypropyl methylcellulose; polyvinylpyrrolidone