Adv Pharm Bull. 2016;6(4): 479-494. doi: 10.15171/apb.2016.062
PMID: 28101455        PMCID: PMC5241406

Review Article

Pharmaceutical Cocrystals: Regulatory and Strategic Aspects, Design and Development

Dipak Dilip Gadade 1 * , Sanjay Sudhakar Pekamwar 1 * ORCID

Cited by CrossRef: 36

1- Raut M, Giri L, Pedireddi V. Supramolecular Assemblies of cis,cis,cis -1,2,4,5-Cyclohexanetetracarboxylic Acid with Various Aza-Donors. ChemistrySelect. 2018;3(11):3194 [Crossref]
2- Kimoto K, Yamamoto M, Karashima M, Hohokabe M, Takeda J, Yamamoto K, Ikeda Y. Pharmaceutical Cocrystal Development of TAK-020 with Enhanced Oral Absorption. Crystals. 2020;10(3):211 [Crossref]
3- Panzade P, Shendarkar G. Pharmaceutical cocrystal: a game changing approach for the administration of old drugs in new crystalline form. Drug Development and Industrial Pharmacy. 2020;46(10):1559 [Crossref]
4- Thimmasetty J, Ghosh T, Nayak N, Raheem A. Oral Bioavailability Enhancement of Paliperidone by the use of Cocrystalization and Precipitation Inhibition. J Pharm Innov. 2021;16(1):160 [Crossref]
5- Harfouche L, Brandel C, Cartigny Y, ter Horst J, Coquerel G, Petit S. Enabling Direct Preferential Crystallization in a Stable Racemic Compound System. Mol Pharmaceutics. 2019;16(11):4670 [Crossref]
6- Wang L, Zhao M, Bu F, Niu Y, Yu Y, Li Y, Yan C, Wu Z. Cocrystallization of Amantadine Hydrochloride with Resveratrol: The First Drug–Nutraceutical Cocrystal Displaying Synergistic Antiviral Activity. Crystal Growth & Design. 2021;21(5):2763 [Crossref]
7- Anand R, Kumar A, Nanda A. Pharmaceutical Co-Crystals - Design, Development and Applications. DDL. 2020;10(3):169 [Crossref]
8- Harfouche L, Couvrat N, Sanselme M, Brandel C, Cartigny Y, Petit S, Coquerel G. Discovery of New Proxyphylline-Based Chiral Cocrystals: Solid State Landscape and Dehydration Mechanism. Crystal Growth & Design. 2020;20(6):3842 [Crossref]
9- Raheem Thayyil A, Juturu T, Nayak S, Kamath S. Pharmaceutical Co-Crystallization: Regulatory Aspects, Design, Characterization, and Applications. Adv Pharm Bull. 2020;10(2):203 [Crossref]
10- Serrano D, Walsh D, O'Connell P, Mugheirbi N, Worku Z, Bolas-Fernandez F, Galiana C, Dea-Ayuela M, Healy A. Optimising the in vitro and in vivo performance of oral cocrystal formulations via spray coating. European Journal of Pharmaceutics and Biopharmaceutics. 2018;124:13 [Crossref]
11- Fontana F, Figueiredo P, Zhang P, Hirvonen J, Liu D, Santos H. Production of pure drug nanocrystals and nano co-crystals by confinement methods. Advanced Drug Delivery Reviews. 2018;131:3 [Crossref]
12- Stainton P, Grecu T, McCabe J, Munshi T, Nauha E, Scowen I, Blagden N. First Comparative Study of the Three Polymorphs of Bis(isonicotinamide) Citric Acid Cocrystals and the Concomitant Salt 4-Carbamoylpyridinium Citrate Isonicotinamide. Crystal Growth & Design. 2018;18(7):4150 [Crossref]
13- Ross S, Ward A, Basford P, McAllister M, Douroumis D. Coprocessing of Pharmaceutical Cocrystals for High Quality and Enhanced Physicochemical Stability. Crystal Growth & Design. 2019;19(2):876 [Crossref]
14- Malamatari M, Ross S, Douroumis D, Velaga S. Experimental cocrystal screening and solution based scale-up cocrystallization methods. Advanced Drug Delivery Reviews. 2017;117:162 [Crossref]
15- Salem A, Nagy S, Pál S, Széchenyi A. Reliability of the Hansen solubility parameters as co-crystal formation prediction tool. International Journal of Pharmaceutics. 2019;558:319 [Crossref]
16- Sarkar N, Aakeröy C. Evaluating hydrogen-bond propensity, hydrogen-bond coordination and hydrogen-bond energy as tools for predicting the outcome of attempted co-crystallisations. Supramolecular Chemistry. 2020;32(2):81 [Crossref]
17- Chamorro Orué A, Boese R, Schauerte C, Merz K. An Experimental and Theoretical Approach to Control Salt vs Cocrystal vs Hybrid Formation—Crystal Engineering of an E/Z-Butenedioic Acid/Phthalazine System. Crystal Growth & Design. 2019;19(3):1616 [Crossref]
18- Bertoni S, Albertini B, Passerini N. Spray Congealing: An Emerging Technology to Prepare Solid Dispersions with Enhanced Oral Bioavailability of Poorly Water Soluble Drugs. Molecules. 2019;24(19):3471 [Crossref]
19- Sandhu B, McLean A, Sinha A, Desper J, Sarjeant A, Vyas S, Reutzel-Edens S, Aakeröy C. Evaluating Competing Intermolecular Interactions through Molecular Electrostatic Potentials and Hydrogen-Bond Propensities. Crystal Growth & Design. 2018;18(1):466 [Crossref]
20- Ren S, Liu M, Hong C, Li G, Sun J, Wang J, Zhang L, Xie Y. The effects of pH, surfactant, ion concentration, coformer, and molecular arrangement on the solubility behavior of myricetin cocrystals. Acta Pharmaceutica Sinica B. 2019;9(1):59 [Crossref]
21- Sarkar N, Sinha A, Aakeröy C. Systematic investigation of hydrogen-bond propensities for informing co-crystal design and assembly. CrystEngComm. 2019;21(40):6048 [Crossref]
22- Diniz L, Franco C, Silva D, Martins L, Carvalho Jr P, Souza M, Reis N, Fernandes C, Diniz R. Multicomponent ionic crystals of diltiazem with dicarboxylic acids toward understanding the structural aspects driving the drug-release. International Journal of Pharmaceutics. 2021;605:120790 [Crossref]
23- Teoh X, bt Mahyuddin F, Ahmad W, Chan S. Formulation strategy of nitrofurantoin: co-crystal or solid dispersion?. Pharmaceutical Development and Technology. 2020;25(2):245 [Crossref]
24- Ngilirabanga J, Rosa P, Aucamp M, Kippie Y, Samsodien H. Dual-drug co-crystal synthesis for synergistic in vitro effect of three key first-line antiretroviral drugs. Journal of Drug Delivery Science and Technology. 2020;60:101958 [Crossref]
25- Hussain E, Kumar R, Choudhary M, Yousuf S. Crystal Engineering of Naturally Occurring Seselin To Obtain Cocrystal with Enhanced Anti-Leishmanial Activity, Hirshfeld Surface Analysis, and Computational Insight. Crystal Growth & Design. 2018;18(8):4628 [Crossref]
26- Roca-Paixão L, Correia N, Affouard F. Affinity prediction computations and mechanosynthesis of carbamazepine based cocrystals. CrystEngComm. 2019;21(45):6991 [Crossref]
27- Tabassum N, Varras P, Arshad F, Choudhary M, Yousuf S. Biological activity tuning of antibacterial urotropine via co-crystallization: synthesis, biological activity evaluation and computational insight. CrystEngComm. 2020;22(20):3439 [Crossref]
28- Long B, Verma V, Ryan K, Padrela L. Generation and physicochemical characterization of posaconazole cocrystals using Gas Antisolvent (GAS) and Supercritical Solvent (CSS) methods. The Journal of Supercritical Fluids. 2021;170:105134 [Crossref]
29- Sathisaran I, Skieneh J, Rohani S, Dalvi S. Curcumin Eutectics with Enhanced Dissolution Rates: Binary Phase Diagrams, Characterization, and Dissolution Studies. J Chem Eng Data. 2018;63(10):3652 [Crossref]
30- Wasim M, Mannan A, Asad M, Amirzada M, Shafique M, Hussain I, Ahad D. Fabrication of Carbamazepine Cocrystals: Characterization, In Vitro and Comparative In Vivo Evaluation. BioMed Research International. 2021;2021:1 [Crossref]
31- Sarkar N, Gonnella N, Krawiec M, Xin D, Aakeröy C. Evaluating the Predictive Abilities of Protocols Based on Hydrogen-Bond Propensity, Molecular Complementarity, and Hydrogen-Bond Energy for Cocrystal Screening. Crystal Growth & Design. 2020;20(11):7320 [Crossref]
32- Sverdlov Arzi R, Sosnik A. Electrohydrodynamic atomization and spray-drying for the production of pure drug nanocrystals and co-crystals. Advanced Drug Delivery Reviews. 2018;131:79 [Crossref]
33- Aitipamula S, Das S. Cocrystal formulations: A case study of topical formulations consisting of ferulic acid cocrystals. European Journal of Pharmaceutics and Biopharmaceutics. 2020;149:95 [Crossref]
34- Zhang X, Xing H, Zhao Y, Ma Z. Pharmaceutical Dispersion Techniques for Dissolution and Bioavailability Enhancement of Poorly Water-Soluble Drugs. Pharmaceutics. 2018;10(3):74 [Crossref]
35- Lopez-Toledano M, Saxena V, Legassie J, Liu H, Ghanta A, Riseman S, Cocilova C, Daak A, Thorsteinsson T, Rabinowicz A, Sancilio F. Advanced Lipid Technologies® (ALT®): A Proven Formulation Platform to Enhance the Bioavailability of Lipophilic Compounds. Journal of Drug Delivery. 2019;2019:1 [Crossref]
36- Fatima S, Kumar R, Choudhary M, Yousuf S. Crystal engineering of exemestane to obtain a co-crystal with enhanced urease inhibition activity. IUCrJ. 2020;7(1):105 [Crossref]
37- Wróblewska A, Śniechowska J, Kaźmierski S, Wielgus E, Bujacz G, Mlostoń G, Chworos A, Suwara J, Potrzebowski M. Application of 1-Hydroxy-4,5-Dimethyl-Imidazole 3-Oxide as Coformer in Formation of Pharmaceutical Cocrystals. Pharmaceutics. 2020;12(4):359 [Crossref]
38- Ghasemi F, Rezvani A, Ghasemi K, Graiff C. Glycine and metformin as new counter ions for mono and dinuclear vanadium(V)-dipicolinic acid complexes based on the insulin-enhancing anions: Synthesis, spectroscopic characterization and crystal structure. Journal of Molecular Structure. 2018;1154:319 [Crossref]
39- Araya-Sibaja A, Fandaruff C, Wilhelm K, Vega-Baudrit J, Guillén-Girón T, Navarro-Hoyos M. Crystal Engineering to Design of Solids: From Single to Multicomponent Organic Materials. MROC. 2020;17(5):518 [Crossref]
40- Patyk-Kaźmierczak E, Kaźmierczak M. A new high-pressure benzocaine polymorph — towards understanding the molecular aggregation in crystals of an important active pharmaceutical ingredient (API). Acta Crystallogr B Struct Sci Cryst Eng Mater. 2020;76(1):56 [Crossref]
41- Nugrahani I, Utami D, Nugraha Y, Uekusa H, Hasianna R, Darusman A. Cocrystal construction between the ethyl ester with parent drug of diclofenac: structural, stability, and anti-inflammatory study. Heliyon. 2019;5(12):e02946 [Crossref]
42- Évora A, Bernardes C, Piedade M, Conceição A, Minas da Piedade M. Energetics of Glycine Cocrystal or Salt Formation with Two Regioisomers: Fumaric Acid and Maleic Acid. Crystal Growth & Design. 2019;19(9):5054 [Crossref]
43- Padrela L, Rodrigues M, Duarte A, Dias A, Braga M, de Sousa H. Supercritical carbon dioxide-based technologies for the production of drug nanoparticles/nanocrystals – A comprehensive review. Advanced Drug Delivery Reviews. 2018;131:22 [Crossref]
44- Dai X, Chen J, Lu T. Pharmaceutical cocrystallization: an effective approach to modulate the physicochemical properties of solid-state drugs. CrystEngComm. 2018;20(36):5292 [Crossref]
45- Sathisaran I, Dalvi S. Engineering Cocrystals of Poorly Water-Soluble Drugs to Enhance Dissolution in Aqueous Medium. Pharmaceutics. 2018;10(3):108 [Crossref]
46- Fulas O, Laferrière A, Ayoub G, Gandrath D, Mottillo C, Titi H, Stein R, Friščić T, Coderre T. Drug-Nutraceutical Co-Crystal and Salts for Making New and Improved Bi-Functional Analgesics. Pharmaceutics. 2020;12(12):1144 [Crossref]
47- Alvani A, Jouyban A, Shayanfar A. The effect of surfactant and polymer on solution stability and solubility of tadalafil-methylparaben cocrystal. Journal of Molecular Liquids. 2019;281:86 [Crossref]
48- Sarkar N, Mitra J, Vittengl M, Berndt L, Aakeröy C. A user-friendly application for predicting the outcome of co-crystallizations. CrystEngComm. 2020;22(41):6776 [Crossref]
49- Nugrahani I, Fisandra F, Horikawa A, Uekusa H. New Sodium Mefenamate – Nicotinamide Multicomponent Crystal Development to Modulate Solubility and Dissolution: Preparation, Structural, and Performance Study. Journal of Pharmaceutical Sciences. 2021; [Crossref]
50- Ngilirabanga J, Aucamp M, Pires Rosa P, Samsodien H. Mechanochemical Synthesis and Physicochemical Characterization of Isoniazid and Pyrazinamide Co-crystals With Glutaric Acid. Front Chem. 2020;8 [Crossref]
51- Islam M, Renner F, Foster K, Oderinde M, Stefanski K, Mitra S. Hydrophilic and Functionalized Nanographene Oxide Incorporated Faster Dissolving Megestrol Acetate. Molecules. 2021;26(7):1972 [Crossref]
52- Pagire S, Seaton C, Paradkar A. Improving Stability of Effervescent Products by Co-Crystal Formation: A Novel Application of Crystal Engineered Citric Acid. Crystal Growth & Design. 2020;20(7):4839 [Crossref]
53- Zhang Z, Yu N, Xue C, Gao S, Deng Z, Li M, Liu C, Castellot J, Han S. Potential Anti-Tumor Drug: Co-Crystal 5-Fluorouracil-nicotinamide. ACS Omega. 2020;5(26):15777 [Crossref]
54- Karimi-Jafari M, Padrela L, Walker G, Croker D. Creating Cocrystals: A Review of Pharmaceutical Cocrystal Preparation Routes and Applications. Crystal Growth & Design. 2018;18(10):6370 [Crossref]
55- Gamekkanda J, Sinha A, Aakeröy C. Cocrystals and Salts of Tetrazole-Based Energetic Materials. Crystal Growth & Design. 2020;20(4):2432 [Crossref]