Abstract
In recent years, pharmaceutical cocrystals as a new solid form have received considerable attention among the applied novel methods for modifying drug substance characteristics. Crystal engineering offers an excellent opportunity to improve physicochemical and pharmacokinetic properties such as solubility, dissolution rate, permeability, bioavailability, biochemical/physical stability, etc. Application of the cocrystal form in the pharmaceutical industry and in academia is becoming a popular method to overcome solubility disadvantages of the active pharmaceutical ingredient (API). Due to manipulation of the API crystalline structure by cocrystal formation, solubility is not the only affected property; some other properties of the newly produced solid form must be considered to fulfill the desired therapeutic efficacy. The stability of the cocrystal in solution is one of these influential features. Regarding the aqueous nature of the gastrointestinal tract, unwanted solution-mediated phase transformation of a cocrystal to a more stable form causes inefficient drug delivery. It may potentially reduce the drug concentration in the circulation. Cocrystal transformation products could be a different polymorph, hydrated form, or mixture of the API and coformer. This review focuses on the solution stability of cocrystals and the effects of various factors such as polymers, surfactants, biorelevant media, organic solvents, and pH.
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