Pharmaceutical Co-crystal: Design, Synthesis And Characterization

Cocrystals of active pharmaceutical ingredients (API) represent a class of crystallineforms that are of interest for their advantageous physicochemical properties and forintellectual property implications.Given that the majority of APIs are fallen intoBiopharmaceutical Classification Scheme (BCS)classification II (low solubility, highpermeability), a particularly great challenge is represented to crystal engineersbecause of both fundamental and applied reasons. APIs are inherently predisposed forself-assembly since their utility is normally the result of the presence of one or morefunctional supramolecular synthons. The methods of crystal engineering could offera flexible approach by introducing another molecular component into the crystallattice, making it possible to improve the physicochemical properties. Increasinginterest in this topic has led to the development of high-throughput (HT) experimentsto screen for cocrystals of APIs. In short, the existence of multiple crystal forms of anAPI affords both challenges and opportunities to the pharmaceutical industry. In thisresearch, paliperidone, iloperidone and vilazodone hydrochloride which are asecond-generation antipsychotic agent approved by the US Food and DrugAdministration (FDA) in2006,2009and2012for the treatment of schizophrenia inadults, was selected to exploit its novel crystal forms with excellent physicochemicaland biological properties. The novel crystal forms Jilin UniversityChina-Cocrystal-1-13(JUC-C1-13) of iloperidone with the corresponding carboxylicacid were obtained using the reaction crystallization method (RCM). The dissolutionand pharmacokinetics studies were performed to evaluate the pharmacokinetic (PK)studies. We selected the cocrystal with the superior pharmaceutical properties andbuild the relationship between the structure and pharmaceutical properties.