title: Cocrystals to facilitate delivery of poorly soluble compounds beyond-rule-of-5.
abstract: Besides enhancing aqueous solubilities, cocrystals have the ability to fine-tune solubility advantage over drug, supersaturation index, and bioavailability. This review presents important facts about cocrystals that set them apart from other solid-state forms of drugs, and a quantitative set of rules for the selection of additives and solution/formulation conditions that predict cocrystal solubility, supersaturation index, and transition points. Cocrystal eutectic constants are shown to be the most important cocrystal property that can be measured once a cocrystal is discovered, and simple relationships are presented that allow for prediction of cocrystal behavior as a function of pH and drug solubilizing agents. Cocrystal eutectic constant is a stability or supersatuation index that: (a) reflects how close or far from equilibrium a cocrystal is, (b) establishes transition points, and (c) provides a quantitative scale of cocrystal true solubility changes over drug. The benefit of this strategy is that a single measurement, that requires little material and time, provides a principled basis to tailor cocrystal supersaturation index by the rational selection of cocrystal formulation, dissolution, and processing conditions.
authors.affiliation: Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor 48109-1065, MI, USA.
authors.forename: Gislaine
authors.initials: G
authors.lastname: Kuminek
authors.affiliation: Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor 48109-1065, MI, USA.
authors.forename: Fengjuan
authors.initials: F
authors.lastname: Cao
authors.affiliation: Programa de Pós-Graduação em Farmácia, Universidade Federal de Santa Catarina, Florianópolis 88040-900, SC, Brazil.
authors.forename: Alanny
authors.initials: A
authors.lastname: Bahia de Oliveira da Rocha
authors.affiliation: Programa de Pós-Graduação em Farmácia, Universidade Federal de Santa Catarina, Florianópolis 88040-900, SC, Brazil.
authors.forename: Simone
authors.initials: S
authors.lastname: Gonçalves Cardoso
authors.affiliation: Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor 48109-1065, MI, USA.
authors.forename: Naír
authors.initials: N
authors.lastname: Rodríguez-Hornedo
mesh_terms: D001682:Biological Availability; D003460:Crystallization; D006863:Hydrogen-Ion Concentration; D004364:Pharmaceutical Preparations / Q000737:chemistry* / Q000378:metabolism*; D012995:Solubility
chemical_list: D004364:Pharmaceutical Preparations
keywords: Biorelevant media; Co-crystal; Cocrystal; Enhancing solubility; Formulation; Solubilizing agent; Supersaturation; Transition point