Creating Cocrystals: A Review of Pharmaceutical Cocrystal Preparation Routes and Applications

Karimi-Jafari, Maryam; Padrela, Luís; Walker, Gavin; Croker, Denise M.

doi:10.1021/acs.cgd.8b00933

Cited by 459 publications

(459 citation statements)

References 138 publications

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“…36 Ternary phase diagram (TPD) is a solute-solute-solvent triangular phase diagram that is used for coformer screening in the solution co-crystallization. 37 Hong et al have used TPD for the successful preparation of myricetin co-crystals. 38…”

Section: Binary and Ternary Phase Diagramsmentioning

confidence: 99%

Pharmaceutical Co-Crystallization: Regulatory Aspects, Design, Characterization, and Applications

et al. 2020

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Pharmaceutical co-crystals are novel class of pharmaceutical substances, which possess an apparent probability of advancement of polished physical properties offering stable and patentable solid forms. These multi-component crystalline forms influence pertinent physicochemical parameters like solubility, dissolution rate, chemical stability, physical stability, etc. which in turn result in the materials with superior properties to those of the free drug. Co-crystallization is a process by which the molecular interactions can be altered to optimize the drug properties. Co-crystals comprise a multicomponent system of active pharmaceutical ingredient (API) with a stoichiometric amount of a pharmaceutically acceptable coformer incorporated in the crystal lattice. By manufacturing pharmaceutical co-crystals, the physicochemical properties of a drug can be improved thus multicomponent crystalline materials have received renewed interest in the current scenario due to the easy administration in the pharmaceutical industry. There is an immense amount of literature available on co-crystals. However, there is a lack of an exhaustive review on a selection of coformers and regulations on co-crystals. The review has made an attempt to bridge this gap. The review also describes the methods used to prepare co-crystals with their characterization. Brief description on the pharmaceutical applications of co-crystals has also been incorporated here. Efforts are made to include reported works on co-crystals, which further help to understand the concept of co-crystals in depth.

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Section: Binary and Ternary Phase Diagramsmentioning

confidence: 99%

Pharmaceutical Co-Crystallization: Regulatory Aspects, Design, Characterization, and Applications

et al. 2020

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“…The basic requirement for a suitable coformer is to be pharmaceutically acceptable, i.e., generally regarded as safe (GRAS) substances. Furthermore, coformers should be relatively cheap, with rather low molecular weight, and possess multiple API-binding sites which can be involved in the formation of strong intermolecular interactions [16].…”

Section: Introductionmentioning

confidence: 99%

Application of 1-Hydroxy-4,5-Dimethyl-Imidazole 3-Oxide as Coformer in Formation of Pharmaceutical Cocrystals

et al. 2020

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Two, well defined binary crystals with 1-Hydroxy-4,5-Dimethyl-Imidazole 3-Oxide (HIMO) as coformer and thiobarbituric acid (TBA) as well barbituric acid (BA) as Active Pharmaceutical Ingredients (APIs) were obtained by cocrystallization (from methanol) or mechanochemically by grinding. The progress of cocrystal formation in a ball mill was monitored by means of high-resolution, solid state NMR spectroscopy. The 13 C CP/MAS, 15 N CP/MAS and 1 H Very Fast (VF) MAS NMR procedures were employed to inspect the tautomeric forms of the APIs, structure elucidation of the coformer and the obtained cocrystals. Single crystal X-ray studies allowed us to define the molecular structure and crystal packing for the coformer as well as the TBA/HIMO and BA/HIMO cocrystals. The intermolecular hydrogen bonding, π-π interactions and CH-π contacts responsible for higher order organization of supramolecular structures were determined. Biological studies of HIMO and the obtained cocrystals suggest that these complexes are not cytotoxic and can potentially be considered as therapeutic materials.

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“…Cocrystals are novel forms of crystals composed of active pharmaceutical ingredients (APIs) and cocrystal coformers (coformers) and are formed through non-ionic interactions [1]. The generation of cocrystals improves not only the physical and mechanical properties of drugs, such as solubility and stability, but also enhances taste masking and intellectual property development [2]. As many poorly water-soluble compounds have been discovered, improving solubility is an important issue in new drug development.…”

Section: Introductionmentioning

confidence: 99%

Physical Characteristics of Cilostazol–Hydroxybenzoic Acid Cocrystals Prepared Using a Spray Drying Method

et al. 2020

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The cocrystal formation of pharmaceuticals can improve the various physical properties of drugs, such as solubility, without the need for chemical modification of the drug substances. In the present study, we prepared cocrystals of cilostazol and additive coformers (derivatives of hydroxybenzoic acid) using a spray drying method. Based on the preparation of the cocrystals of cilostazol and the coformers as reported previously, the characteristics of the cilostazol cocrystals prepared using solvent evaporation, slurry, and spray drying methods were compared. The physical characterization revealed that the spray drying method successfully produced cilostazol–4-hydroxybenzoic acid and cilostazol–2,4-dihydroxybenzoic acid cocrystals, whereas samples of cocrystals of cilostazol and 2,5-dihydroxybenzoic acid produced via the spray drying process appeared to contain coformer polymorphs. The dissolution of cilostazol was improved using the spray-dried cocrystal samples composed of coformers compared to samples prepared using cilostazol alone or a physical mixture. The present results provide useful information regarding the manufacture of cilostazol cocrystals and pharmaceutical cocrystals via spray drying in large-batch production.

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Creating Cocrystals: A Review of Pharmaceutical Cocrystal Preparation Routes and Applications

Cited by 459 publications

References 138 publications

Pharmaceutical Co-Crystallization: Regulatory Aspects, Design, Characterization, and Applications

Pharmaceutical Co-Crystallization: Regulatory Aspects, Design, Characterization, and Applications

Application of 1-Hydroxy-4,5-Dimethyl-Imidazole 3-Oxide as Coformer in Formation of Pharmaceutical Cocrystals

Physical Characteristics of Cilostazol–Hydroxybenzoic Acid Cocrystals Prepared Using a Spray Drying Method

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