title: A Promising New Method to Estimate Drug-Polymer Solubility at Room Temperature.
abstract: The established methods to predict drug-polymer solubility at room temperature either rely on extrapolation over a long temperature range or are limited by the availability of a liquid analogue of the polymer. To overcome these issues, this work investigated a new methodology where the drug-polymer solubility is estimated from the solubility of the drug in a solution of the polymer at room temperature using the shake-flask method. Thus, the new polymer in solution method does not rely on temperature extrapolations and only requires the polymer and a solvent, in which the polymer is soluble, that does not affect the molecular structure of the drug and polymer relative to that in the solid state. Consequently, as this method has the potential to provide fast and precise estimates of drug-polymer solubility at room temperature, we encourage the scientific community to further investigate this principle both fundamentally and practically.
authors.affiliation: Pharmaceutical Science and CMC Biologics, H. Lundbeck A/S, Valby DK-2500, Denmark; Institute of Pharmacy and Biochemistry, Johannes Gutenberg University of Mainz, Mainz D-55128, Germany.
authors.forename: Matthias Manne
authors.initials: MM
authors.lastname: Knopp
authors.affiliation: Institute of Pharmacy and Biochemistry, Johannes Gutenberg University of Mainz, Mainz D-55128, Germany.
authors.forename: Natasha
authors.initials: N
authors.lastname: Gannon
authors.affiliation: Institute of Pharmacy and Biochemistry, Johannes Gutenberg University of Mainz, Mainz D-55128, Germany.
authors.forename: Ilona
authors.initials: I
authors.lastname: Porsch
authors.affiliation: Pharmaceutical Science and CMC Biologics, H. Lundbeck A/S, Valby DK-2500, Denmark; Department of Pharmacy, University of Copenhagen, Copenhagen DK-2100, Denmark.
authors.forename: Malte Bille
authors.initials: MB
authors.lastname: Rask
authors.affiliation: Pharmaceutical Science and CMC Biologics, H. Lundbeck A/S, Valby DK-2500, Denmark.
authors.forename: Niels Erik
authors.initials: NE
authors.lastname: Olesen
authors.affiliation: Institute of Pharmacy and Biochemistry, Johannes Gutenberg University of Mainz, Mainz D-55128, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Langguth
authors.affiliation: Pharmaceutical Science and CMC Biologics, H. Lundbeck A/S, Valby DK-2500, Denmark; Department of Pharmacy, University of Copenhagen, Copenhagen DK-2100, Denmark. Electronic address: rhol@lundbeck.com.
authors.forename: René
authors.initials: R
authors.lastname: Holm
authors.affiliation: Department of Pharmacy, University of Copenhagen, Copenhagen DK-2100, Denmark.
authors.forename: Thomas
authors.initials: T
authors.lastname: Rades
mesh_terms: D000082:Acetaminophen / Q000737:chemistry; D000068579:Celecoxib / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D002701:Chloramphenicol / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D012995:Solubility; D012996:Solutions; D044366:Transition Temperature
chemical_list: D004364:Pharmaceutical Preparations; D011108:Polymers; D012996:Solutions; D000082:Acetaminophen; D002701:Chloramphenicol; D000068579:Celecoxib
keywords: Flory-Huggins; amorphous solid dispersion; polymers; poorly soluble drugs; shake-flask method; solubility; solubility enhancement; thermal analysis