title: Mechanical Properties and Tableting Behavior of Amorphous Solid Dispersions.
abstract: Amorphous solid dispersions (ASDs) consisting of acetaminophen (APAP) and copovidone were systematically studied to identify effects of drug loading and moisture content on mechanical properties, thermal properties, and tableting behavior. ASDs containing APAP at different levels were prepared by film casting and characterized by differential scanning calorimetry and nanoindentation. The glass transition temperature (Tg) continuously decreased with increasing amount of APAP, but the hardness of ASDs was increased at a low APAP content and reduced at high APAP content. This in turn significantly influenced tablet quality. Water reduced both the hardness and Tgof ASDs, and the APAP loading level corresponding to the transition to the softening mechanism was lower at a higher relative humidity. Overall, the mechanical properties, rather than the thermal properties, better represent the plasticization/antiplasticization effect of small molecule to ASDs.
authors: Pharmaceutical Materials Science & Engineering Laboratory, Department of Pharmaceutics, University of Minnesota, Minneapolis, Minnesota 55455.
authors: Sarsvat
authors: S
authors: Patel
authors: Pharmaceutical Materials Science & Engineering Laboratory, Department of Pharmaceutics, University of Minnesota, Minneapolis, Minnesota 55455.
authors: Xiang
authors: X
authors: Kou
authors: Drug Product Development, Research and Development, AbbVie Inc., North Chicago, Illinois 60064.
authors: Hao Helen
authors: HH
authors: Hou
authors: Drug Product Development, Research and Development, AbbVie Inc., North Chicago, Illinois 60064.
authors: Ye Bill
authors: YB
authors: Huang
authors: Drug Product Development, Research and Development, AbbVie Inc., North Chicago, Illinois 60064.
authors: John C
authors: JC
authors: Strong
authors: Drug Product Development, Research and Development, AbbVie Inc., North Chicago, Illinois 60064. Electronic address: geoff.gz.zhang@abbvie.com.
authors: Geoff G Z
authors: GGZ
authors: Zhang
authors: Pharmaceutical Materials Science & Engineering Laboratory, Department of Pharmaceutics, University of Minnesota, Minneapolis, Minnesota 55455. Electronic address: sunx0053@umn.edu.
authors: Changquan Calvin
authors: CC
authors: Sun
mesh_terms: D000082:Acetaminophen / Q000008:administration & dosage* / Q000737:chemistry; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage* / Q000737:chemistry; D003460:Crystallization; D004339:Drug Compounding; D006244:Hardness; D006813:Humidity; D044367:Phase Transition; D011759:Pyrrolidines / Q000737:chemistry*; D012995:Solubility; D013607:Tablets; D044366:Transition Temperature; D014753:Vinyl Compounds / Q000737:chemistry*; D014867:Water / Q000737:chemistry
chemical_list: D018712:Analgesics, Non-Narcotic; D011759:Pyrrolidines; D013607:Tablets; D014753:Vinyl Compounds; C402301:poly(vinylpyrrolidone-co-vinyl-acetate); D014867:Water; D000082:Acetaminophen
keywords: amorphous; compaction; dispersion; glass transition; hardness; mechanical properties; physical characterization; solid state; tablet