title: Impact of pharmaceutical cocrystals: the effects on drug pharmacokinetics.
abstract: BACKGROUND
  Pharmaceutical cocrystallization has emerged in the past decade as a new strategy to enhance the clinical performance of orally administered drugs. A pharmaceutical cocrystal is a multi-component crystalline material in which the active pharmaceutical ingredient is in a stoichiometric ratio with a second compound that is generally a solid under ambient conditions. The resulting cocrystal exhibits different solid-state thermodynamics, leading to changes in physicochemical properties that offer the potential to significantly modify drug pharmacokinetics.
  
  
  METHODS
  The impact of cocrystallization upon drug pharmacokinetics has not yet been well delineated. Herein, we compile previously published data to address two salient questions: what effect does cocrystallization impart upon physicochemical properties of a drug substance and to what degree can those effects impact its pharmacokinetics.
  
  
  CONCLUSIONS
  Cocrystals can impact various aspects of drug pharmacokinetics, including, but not limited to, drug absorption. The diversity of solid forms offered through cocrystallization can facilitate drastic changes in solubility and pharmacokinetics. Therefore, it is unsurprising that cocrystal screening is now a routine step in early-stage drug development. With the increasing recognition of pharmaceutical cocrystals from clinical, regulatory and legal perspectives, the systematic commercialization of cocrystal containing drug products is just a matter of time.
authors.affiliation: Thar Pharmaceuticals, Inc. , 3802 Spectrum Boulevard, Suite 120, Tampa, FL 33612 , USA +1 813 978 3980 ; nshan@tharpharma.com.
authors.forename: Ning
authors.initials: N
authors.lastname: Shan
authors.forename: Miranda L
authors.initials: ML
authors.lastname: Perry
authors.forename: David R
authors.initials: DR
authors.lastname: Weyna
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Zaworotko
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002626:Chemistry, Pharmaceutical; D003460:Crystallization; D015195:Drug Design; D006801:Humans; D004364:Pharmaceutical Preparations / Q000737:chemistry* / Q000378:metabolism; D010599:Pharmacokinetics; D012995:Solubility; D013816:Thermodynamics
chemical_list: D004364:Pharmaceutical Preparations
keywords: AUC; Cmax; Tmax; cocrystal; crystal engineering; drug development; pharmacokinetics; solubility