ISSN: 2228-5881 eISSN: 2251-7308

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 *

Cited by CrossRef: 110

1- Jiang X, Yu K, Nam D, Oh J. A Population Pharmacokinetic Study to Compare a Novel Empagliflozin L-Proline Formulation with Its Conventional Formulation in Healthy Subjects. Pharmaceuticals. 2024;17(4):522 [Crossref]

2- 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]

3- Ai Q, Norquist A, Schrier J. Predicting compositional changes of organic–inorganic hybrid materials with Augmented CycleGAN. Digital Discovery. 2022;1(3):255 [Crossref]

4- Pekamwar S, Kulkarni D. DEVELOPMENT AND EVALUATION OF BICOMPONENT COCRYSTALS OF ACECLOFENAC FOR EFFICIENT DRUG DELIVERY WITH ENHANCED SOLUBILITY AND IMPROVED DISSOLUTION. IND DRU. 2021;58(08):54 [Crossref]

5- Zerrouki K, Bouchene R, Tüzün B, Retailleau P. Novel supramolecular co-crystal of 8-hydroxyquinoline with acetone-(2,4-dinitrophenyl)hydrazone: One pot synthesis, structural characterization, Hirshfeld surface and energy framework analysis, computational investigation and molecular docking study. Journal of Molecular Structure. 2024;1300:137290 [Crossref]

6- Anand R, Kumar A, Nanda A. Pharmaceutical Co-Crystals - Design, Development and Applications. DDL. 2020;10(3):169 [Crossref]

7- 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]

8- 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]

9- Sabouri S, Shayanfar A. Effects of Surfactant and Polymer on Thermodynamic Solubility and Solution Stability of Carbamazepine–Cinnamic Acid Cocrystal. Pharm Chem J. 2022;56(7):913 [Crossref]

10- Zochedh A, Chandran K, Shunmuganarayanan A, Sultan A. Exploring the Synergistic Effect of Tegafur-Syringic Acid Adduct Against Breast Cancer through DFT Computation, Spectroscopy, Pharmacokinetics and Molecular Docking Simulation. Polycyclic Aromatic Compounds. 2024;44(4):2153 [Crossref]

11- Chauhan V, Mardia R, Patel M, Suhagia B, Parmar K. Technical and Formulation Aspects of Pharmaceutical Co‐Crystallization: A Systematic Review. ChemistrySelect. 2022;7(37) [Crossref]

12- 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]

13- 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]

14- Rana M, Garai A, Nangia A. Cocrystals and Salts of Milrinone with Fluoro Coformers: Improving Drug Dissolution and Diffusion and Calculating Normalized Diffusion for Pharmaceutical Cocrystals. Crystal Growth & Design. 2023;23(9):6461 [Crossref]

15- Prashanth J, Voronin A, Surov A, Balasubramanian S. Design of pyrazine cocrystals of enzalutamide: a lead from 1,4-dioxane solvates. CrystEngComm. 2024;26(28):3851 [Crossref]

16- 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]

17- 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]

18- 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]

19- Gaur R. Polymorphism in parabanic acid-urea cocrystals governed by supramolecular synthons: a comparative analysis. CrystEngComm. 2023;25(33):4680 [Crossref]

20- 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]

21- Zhou H, Duan C, Qin H, Huang C, Hou J, Chen Y, Zhu J, Xu C, Jin J, Zhuang T. Synthesis and structural characterization of a novel palbociclib-kaempferol cocrystal with improved tabletability and synergistic antitumor activity. Journal of Molecular Structure. 2023;1281:135101 [Crossref]

22- 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]

23- Tharik A, Meyyanathan S. Recent Patents of Pharmaceutical Co-Crystals: Product Development on Anti-Cancer Drugs and Beyond. PRA. 2023;18(3):246 [Crossref]

24- 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]

25- 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]

26- Doloking H, Syamsi Dhuha N, Nurjannah N. Formation, Characterization and In vitro Dissolution studies of Piroxicam-Malic Acid Cocrystals. RJPT. 2024;:3061 [Crossref]

27- 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]

28- 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]

29- Kenguva G, Rekha Rout S, Shaikh T, Baidya D, Shelke N, Sanphui P, Dandela R. Structural insights into ketanserin salts with aliphatic acids and their physiochemical properties. CrystEngComm. 2024;26(44):6260 [Crossref]

30- Stainton P, Nauha E, Grecu T, McCabe J, Munshi T, Scowen I, Chan H, Nilsson S, Blagden N. Chameleon Behavior of a New Salt of 3-(Aminocarbonyl) Pyridinium Malonate and Implications for Polymorphism on the Salt/Cocrystal Continuum. Crystal Growth & Design. 2022;22(3):1665 [Crossref]

31- 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]

32- 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]

33- Feliciano I, Silva D, Piedade M, Bernardes C, Minas da Piedade M. First and Second Dissociation Enthalpies in Bi-Component Crystals Consisting of Maleic Acid and L-Phenylalanine. Molecules. 2021;26(18):5714 [Crossref]

34- A, I, N, S. Pharmaceutical cocrystal and their role in improving solid state properties of active pharmaceutical ingredients. AJPS. 2023;23(2):180 [Crossref]

35- 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]

36- Akki P, Latwade R, Akki K. SOLUBILITY ENHANCEMENT TECHNIQUE FOR BCS CLASS II DRUG - ONDANSETRON HYDROCHLORIDE BY CO-CRYSTALLIZATION METHOD. IND DRU. 2024;61(08):28 [Crossref]

37- Han X, Liu M, Huang Z, Huang H, Long X, Tan B. Theoretical Calculation of Cocrystal Components for Explosives: A Similarity Function of Energetic Supramolecules. Crystal Growth & Design. 2022;22(1):293 [Crossref]

38- Nagamatsu D, Ando S, Fujimura Y, Miyano T, Sugita K, Ueda H. Formation of Hemihydrate Crystal form Overcomes Milling Issue Induced by Exposed Functional Groups on Cleavage Plane for a Y5 Receptor Antagonist of Neuropeptide Y. Journal of Pharmaceutical Sciences. 2023;112(9):2516 [Crossref]

39- 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]

40- Manin A, Boycov D, Simonova O, Volkova T, Churakov A, Perlovich G. Formation Thermodynamics of Carbamazepine with Benzamide, Para-Hydroxybenzamide and Isonicotinamide Cocrystals: Experimental and Theoretical Study. Pharmaceutics. 2022;14(9):1881 [Crossref]

41- 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]

42- Sathisaran I, Dalvi S. Engineering Cocrystals of Poorly Water-Soluble Drugs to Enhance Dissolution in Aqueous Medium. Pharmaceutics. 2018;10(3):108 [Crossref]

43- 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]

44- 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;110(9):3246 [Crossref]

45- 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]

46- Wisudyaningsih B, Sallama S, Siswandono S, Setyawan D. The Effect of pH and Cocrystal Quercetin-Isonicotinamide on Quercetin Solubility and its Thermodynamic. RJPT. 2021;:4657 [Crossref]

47- 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]

48- Shahbaz M, Khan U, Chaudhary M, Yousuf S. A new bioactive cocrystal of coumarin-3-carboxylic acid and thiourea: detailed structural features and biological activity studies. Acta Crystallogr C Struct Chem. 2022;78(3):192 [Crossref]

49- 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]

50- Kalantri S, Yadav M. Advances in Carbamazepine Cocrystals: A Review. Cryst Res Technol. 2024;59(4) [Crossref]

51- 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]

52- Kara D, Rathnanand M. Cocrystals and Drug–Drug Cocrystals of Anticancer Drugs: A Perception towards Screening Techniques, Preparation, and Enhancement of Drug Properties. Crystals. 2022;12(10):1337 [Crossref]

53- Piccirillo G, Aroso R, Baptista J, A. E. Castro R, da Silva G, Calvete M, Pereira M, Canotilho J, Ermelinda S. Eusébio M. Trimethoprim-Based multicomponent solid Systems: Mechanochemical Screening, characterization and antibacterial activity assessment. International Journal of Pharmaceutics. 2024;661:124416 [Crossref]

54- 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]

55- 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]

56- 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]

57- Srivastava A, Prajapati P, Kale D, Tandon P, Bansal A. Unveiling spectroscopic behaviour and molecular features (DFT studies) of Exemestane-maleic acid cocrystal as model multicomponent system. Journal of Molecular Structure. 2025;1319:139471 [Crossref]

58- 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]

59- Salih Z, Al-Khedairy E. Designing and evaluation of ebastine–benzamide cocrystals. F1000Res. 2023;12:1449 [Crossref]

60- 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]

61- 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]

62- 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]

63- 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]

64- Islam M, Mitra S. Microwave Synthesis of Nanostructured Functionalized Polylactic Acid (nfPLA) for Incorporation Into a Drug Crystals to Enhance Their Dissolution. Journal of Pharmaceutical Sciences. 2023;112(8):2260 [Crossref]

65- 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]

66- Saikia B, Pathak D, Sarma B. Variable stoichiometry cocrystals: occurrence and significance. CrystEngComm. 2021;23(26):4583 [Crossref]

67- Şen N, Pons J, Kurtay G, Yüksel B, Nazir H, Khumsri A, Atakol O. New explosive materials through covalent and non-covalent synthesis: Investigation of explosive properties of trinitrotoluene: Acridine and picric acid: Acridine. Journal of Molecular Structure. 2023;1292:136080 [Crossref]

68- 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]

69- 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]

70- Charoenchaitrakool M, Roubroum T, Sudsakorn K. Processing of a novel mefenamic acid−paracetamol−nicotinamide cocrystal using gas anti-solvent process. Journal of CO2 Utilization. 2022;62:102080 [Crossref]

71- 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]

72- 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]

73- Diniz L, Carvalho P, Souza M, Diniz R, Fernandes C. Highly Soluble Dacarbazine Multicomponent Crystals Less Prone to Photodegradation. Mol Pharmaceutics. 2024;21(7):3661 [Crossref]

74- Madanayake S, Manipura A, Thakuria R, Adassooriya N. Opportunities and Challenges in Mechanochemical Cocrystallization toward Scaled-Up Pharmaceutical Manufacturing. Org Process Res Dev. 2023;27(3):409 [Crossref]

75- 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]

76- Kudo T, Miura S, Takatori K, Titapiwatanakun V, Palanisamy V, Yamamoto K, Ikeda Y, Fukami T. Monitoring the Dissolution Behavior of Novel Pharmaceutical Cocrystals Consisting of Antimalarial Drug Artemisinin with Probe-Type Low-Frequency Raman Spectrometer. Appl Spectrosc. 2024;78(11):1125 [Crossref]

77- Stevens J. Colorful 4,4-Bipyridine–Squaric Acid Multicomponent Complexes with Varying Degrees of Proton Transfer: Exploring the Nature of New Form IV in the Salt Co-Crystal Continuum. Crystal Growth & Design. 2022;22(1):779 [Crossref]

78- Roca-Paixão L, Correia N, Affouard F. Affinity prediction computations and mechanosynthesis of carbamazepine based cocrystals. CrystEngComm. 2019;21(45):6991 [Crossref]

79- Tabassum N, Varras P, Arshad F, Choudhary M, Yousuf S. Biological activity tuning of antibacterial urotropineviaco-crystallization: synthesis, biological activity evaluation and computational insight. CrystEngComm. 2020;22(20):3439 [Crossref]

80- 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]

81- 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]

82- Zhao W, Li Q, He P, Li C, Aryal M, Fabiilli M, Xiao H. Charge balanced aggregation: A universal approach to aqueous organic nanocrystals. Journal of Controlled Release. 2024;375:552 [Crossref]

83- 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]

84- Sarangi S, Remya P, Damodharan N. Advances in solvent based cocrystallization: Bridging the gap between theory and practice. Journal of Drug Delivery Science and Technology. 2024;95:105619 [Crossref]

85- 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]

86- 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]

87- Yu Y, Liu L, Bu F, Li Y, Yan C, Wu Z. A novice cocrystal nanomicelle formulation of 5-fluorouracil with proline: The design, self-assembly and in vitro/vivo biopharmaceutical characteristics. International Journal of Pharmaceutics. 2022;617:121635 [Crossref]

88- Qi L, Li C, Bai Y, Ye Y, Xiao Y, Xuanyuan S, Hao H, Xie C. Effect of functional group position in co-formers and solvent on cocrystal polymorphism/stoichiomorphism: a case study. Journal of Molecular Liquids. 2023;388:122741 [Crossref]

89- 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]

90- Oliveira P, Aguiar G, Siebel A, Müller L, Lerin L, Botti G, Bianchi A, Bernardi T, Gentili V, Rizzo R, Pavan B, Dalpiaz A, Trapella C, Oliveira J. Synthesis of naringenin-betaine cocrystal by gas antisolvent technique and cell models for in vitro permeation studies. Journal of Drug Delivery Science and Technology. 2024;96:105671 [Crossref]

91- Tuksar M, Topić E, Rubčić M, Meštrović E. Exploring Salts of Memantine with Inorganic Anions: From Polymorphism and Solid-State Transitions to Potential for Drug Formulations. Mol Pharmaceutics. 2024;21(9):4700 [Crossref]

92- 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]

93- 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]

94- 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]

95- Sahoo P. Cocrystallizing and Codelivering Complementary Drugs to Multidrugresistant Tuberculosis Bacteria in Perfecting Multidrug Therapy. CTMC. 2023;23(19):1850 [Crossref]

96- 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]

97- Dhondale M, Thakor P, Nambiar A, Singh M, Agrawal A, Shastri N, Kumar D. Co-Crystallization Approach to Enhance the Stability of Moisture-Sensitive Drugs. Pharmaceutics. 2023;15(1):189 [Crossref]

98- 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]

99- Nijhawan M, Saxena T, Dhyagala S, Sailaja G, Aleti R. Posaconazole-glutaric acid cocrystal tablet with improved Dissolution rate. RJPT. 2024;:1771 [Crossref]

100- Gamekkanda J, Sinha A, Aakeröy C. Cocrystals and Salts of Tetrazole-Based Energetic Materials. Crystal Growth & Design. 2020;20(4):2432 [Crossref]

101- Poka M, Milne M, Wessels A, Aucamp M. Sugars and Polyols of Natural Origin as Carriers for Solubility and Dissolution Enhancement. Pharmaceutics. 2023;15(11):2557 [Crossref]