CO-CRYSTALS: A REVIEW
Abstract
In development of new product major constraints are poor aqueous solubility and low oral bioavailability. Crystallization is one the approach has been used for enhancement of solubility of poorly aqueous soluble drugs also helps to improve physicochemical properties such as melting point, tabletability, solubility, stability, bioavailability and permeability with preserving the pharmacological properties of the active pharmaceutical ingredient. Different methods have been used for the synthesis of cocrystal such as grinding, slurry, antisolvent, hot melt extrusion, sonocrystallization, supercritical fluid, spray drying etc. The article highlights the co-crystallization, its methods and significance.
DOI
https://doi.org/10.22270/jddt.v8i6-s.2194References
Babu NJ and Nangia A. Solubility advantage of amorphous drugs and pharmaceutical cocrystals. Cryst Growth Des 2011; 11(26): 62-79.
Fong SYK, Ibisogly A, Bauer-Brandl A. Solubility enhancement of BCS class-II drug by solid phospholipid dispersions: Spray drying versus freeze-drying. Int J Pharm 2015; 496:382-91.
Jones W, Motherwell WDS, Trask AV. Pharmaceutical co-crystals: An Emerging approach to physical property enhancement. MRS Bull 2006; 31:875-879.
Zaworotko M. Crystal engineering of co-crystals and their relevance to pharmaceuticals and solid-state chemistry. Acta Cryst 2008; 64:11-12.
Rodríguez-Hornedo N, Nehm SJ, Jayasankar A, Cocrystals: design, properties and formation mechanisms, In Encyclopedia of Pharmaceutical Technology, 3rd ed, Taylor & Francis, London, 2007; 615-635.
Schultheiss N, Newman A. Pharmaceutical co-crystals and their physicochemical properties. Cryst Growth Des.2009; 9:2950–2967.
Tiekink ERT, Vittal JJ (Editors). Frontiers in Crystal Engineering, John Wiley & Sons, Ltd, 2006, Chapter 2: Crystal Engineering of Pharmaceutical Co-crystals, 25-50.
Vishweshwar P, McMahon JA, Bis JA, Zaworotko MJ. Pharmaceutical co-crystals J Pharm Sci 2006; 95:499-516.
Remenar JF, Morissette SL, Peterson ML, Moulton B, MacPhee JM, Guzmán H, Almarsson O, Crystal engineering of novel co-crystals of a triazole drug with 1,4- dicarboxylic acids. J Am ChemSoc 2003; 125(8):456-8457.
Almarsson Ö, Zaworotko MJ. Crystal engineering of the composition of pharmaceutical phases. Do pharmaceutical co-crystals represent a new path to improved medicines? ChemCommun 2004; 1889-1896.
Morissette SL, Almarsson O, Peterson ML, Remenar JF, Read MJ, Lemmo AV, et al. High-throughput crystallization: polymorphs, salts, cocrystals and solvates of pharmaceutical solids. Adv Drug Deliv Rev 2004; 56:275-300.
Sekhon BS. Pharmaceutical cocrystals - An update. Chem Inform 2013; 44:62
Bolla G, Nangia A. Pharmaceutical cocrystals: walking the talk. ChemCommun 2016; 42-60.
Shan N, Zaworotko MJ. The role of cocrystals in pharmaceutical sciences. Drug Discov Today 2008; 13:440-46.
Abourahma H, Cocuzza DS, Melendez J, Urban JM. Pyrazinamide cocrystals and the search for polymorphs. CrystEngComm 2011; 13:1-22.
Batisai E, Ayamine A, Kilinkissa OEY, Bathori N. Melting point-solubility-structure correlations in multicomponent crystal containing fumaric or adipic acid. Cryst Eng Comm 2014:16:9992-8.
Zhang H, Zhu Y , Qiao N, Chen Y, Gao L. Preparation and Characterization of Carbamazepine Cocrystal in Polymer Solution, Pharmaceutics 2017; 9:1-13
Jadhav A, Pore Y. Physiscochemical and micromeretics studies on Feofibrate cocrystal, Journal of pharm. Sci. tech. mgmt. 2016; 2(1)
Panzade P, Shendarkar G, Shaikh S, Rathi P. Pharmaceutical Cocrystal of Piroxicam: Design, Formulation and Evaluation. Adv Pharm Bull. 2017; 7(3):399-408
Zhouab Z, Lia W et al. Resveratrol cocrystals with enhanced solubility and tabletability. International Journal of Pharmaceutics. 2016; 509(1–2):391-399
Latif S, Abbas N, Hussain A, Arshad M S, Bukhari N I, Afzal H, Riffat S, Ahmad Z, Development of paracetamol-caffeine co-crystals to improve compressional, formulation and in vivo performance, Drug Development and Industrial Pharmacy, 2018; 44(7):1099-1108.
Mounika P, Vijaya Raj S, Divya1 G. A. Gowramma2 and G.Vijayamma3, Preparation and Characterization of Novel Co-Crystal Forms of Fexofenadine, International Journal of Innovative Pharmaceutical Research. 2015; 6(1):458-463.
Sopyan I, Fudholi A, Muchtaridi M, Sari I P, Simvastatin-nicotinamide co-crystal: design, preparation and preliminary characterization, Tropical Journal of Pharmaceutical Research. 2017; 16 (2):297-303
Chadha R, Saini A, Arora P, Chanda S, Jain D, Cocrystals Of Efavirenz With Selected Coformers: Preparation And Characterization, International Journal of Pharmacy and Pharmaceutical Sciences, 2012; 4(2).
Bagde SA, Upadhye KP, Dixit GR, Bakhle SS., Formulation and Evaluation of Co-Crystals of Poorly Water Soluble Drug, 2017.
Rajurkar VG, Aucharmal AL, Dethe S, Development of Ezogabine Co Crystal Formation: An Efficient Approach to Enhance Aqueous Solubility, British Biomedical Bulletin, 2015
Muddukrishna Bs, Dengale Sj. Shenoy Gg, Bhat, Preparation, Solid State Characterisation Of Paclitaxel And Naringen Cocrystals With Improved Solubility, International Journal of Applied Pharmaceutics. 2016; 8(4).
Panzade P, Shendarkar G, Shaikh S, Rathi PB, Adv Pharm Bull,Pharmaceutical Cocrystal of Piroxicam: Design, Formulation and Evaluation 2017; 7(3):399-408
Muddukrishna BS, Aithal K, Pai A, Preparation, Solid State Characterization of Etraverine Co-Crystals with Improved Solubility for the Treatment of Human Immunodeficiency Virus International Journal of Pharmacological and Pharmaceutical Sciences. 2017; 11(1).
Gopi SP, Banik M, Desiraju GR. New Cocrystals of Hydrochlorothiazide: Optimizing Solubility and Membrane Diffusivity Crystal Growth & Design. 2016.
Reddy MN, Anusha P. Development and Characterisation of Gliclazide Cocrystals International Journal of Pharmacy and Biological Sciences V2018; 8(1):22-32
Rahim SA, Rahman FANasir, ENEM., Ramle NA. Carbamazepine Co-crystal Screening with Dicarboxylic Acids Co-Crystal Formers International Journal of Chemical and Molecular Engineering. 2015; 9(5).
Gadade DD, Pekamwar SS, Lahot SR., Patn SD, Sarode MC. Cocrystallization of Etodolac: Prediction of Cocrystallization, Synthesis, Solid State Characterization and In Vitro Drug Release , Marmara Pharmaceutical Journal, 2017; 21:78-88.
Huang Y, Zhang B, Gao Y, Zhang J, Shi L. Nicotinamide Cocrystal with Enhanced Solubility, Dissolution, and Oral Bioavailability. 2014.
Rajbhar P, Sahu AK., Gautam SS., Prasad RK, Singh V, Nair SK, Formulation and Evaluation of Clarithromycin CoCrystals Tablets Dosage Forms to Enhance the Bioavailability. The Pharma Innovation Journal. 2016; 5(6):05-13
Zhang H, Zhu Y, Qiao N, Chen Y, Gao L, Preparation and Characterization of Carbamazepine Cocrystal in Polymer Solution, Pharmaceutics. 2017; 9(54):1-13
Jung S, Choi I, Kim W. Liquid-Assisted Grinding to Prepare a Cocrystal of Adefovir Dipivoxil Thermodynamically Less Stable than Its Neat Phase. Crystals 2015; 5:583-591
Othman MF, Jamburi N, Anuar N, Rahim SA, Rohalim NH. Ibuprofen-amino acids co-crystal screening via co-grinding methods, MATEC Web Conf. 2016; 69
Payghan AS. Preparation and Characterization of Molecular Complexes of Fenofibrate Cocrystal. Asian Journal of Pharmaceutics. 2017; 11(4).
Setyawan D, Sari R, Yusuf H, Primaharinastiti R. Preparation and Characterization of Artesunate - Nicotinamide Cocrystal by Solvent Evaporation and Slurry Method. Asian J Pharm Clin Res, 2014; 7(1):62-65.
Takata N, Shiraki K, Takano R, Hayashi Y, Terada K. Cocrystal Screening of Stanolone and Mestanolone Using Slurry Crystallization, Cryst. Growth De.2008; 8(8): 3032–3037
Apshingekar PP, Aher S, Kelly AL, Brown EC, Paradkar A. Synthesis of Caffeine/Maleic Acid Co-crystal by Ultrasound-assisted Slurry Co-crystallization, Journal of Pharmaceutical Sciences. 2017; 106(1):66-70
Erizal Z, Yeyet Cs, Sundani N S, Auzal H, Hidehiro U, Kotaro F, Cocrystalline Phase Transformation of Binary Mixture of Trimethoprim and Sulfamethoxazole by Slurry Technique, Asian Journal of Pharmaceutical and Clinical Research. 2010; 3(4).
Momoko N, Shoji K, Hiroshi T, Cocrystal production method reducing deposition risk of undesired single component crystals in anti-solvent cocrystallization, Journal of Industrial and Engineering Chemistry. 2016; 36:40–43
Chuna N, Wang I, Min-JL, Yun-Tk, Sangkil L, Woo SK, Guang JC, Characteristics of indomethacin–saccharin (IMC–SAC) co-crystals prepared by an anti-solvent crystallization process, European Journal of Pharmaceutics and Biopharmaceutics. 2013; 85(3):854-861
Jeong-WS, Kyu-MH, Sung-HL, Dong-WK. Preparation and characterization of adefovir dipivoxil–stearic acid cocrystal with enhanced physicochemical properties, Pharmaceutical Development and Technology. 2017.
Li S, Yu T, Tian Y, Lagan C, Jones DS, Andrews GP Mechanochemical Synthesis of Pharmaceutical Cocrystal Suspensions via Hot Melt Extrusion: Enhancing Cocrystal Yield. Mol Pharm. 2017.
Kevin B, Andrew O, Rodolfo P, Matrix-Assisted Cocrystallization (MAC) Simultaneous Production and Formulation of Pharmaceutical Cocrystals by Hot-Melt Extrusion. Journal of Pharmaceutical Sciences. 2014; 103(9):2904-2910
Kumar S, Nanda A. Pharmaceutical Cocrystals: An Overview, Indian J Pharm Sci 2017; 79(6):858-871
Apshingekar PP, Aher S, Kelly AL, Brown EC, Paradkar A. Synthesis of Caffeine/Maleic Acid Co-crystal by Ultrasound-assisted Slurry Co-crystallization, Journal of Pharmaceutical Sciences. 2017; 106(1):66-70
Shikhar A, Mohan M, Simerdeep Singh B, Gupta E, Formulation development of Carbamazepine–Nicotinamide co-crystals complexed with γ-cyclodextrin using supercritical fluid process, The Journal of Supercritical Fluids. 2011; 55(3):1070-1078
Courtney A. Ober, Ram B. Gupta, Formation of Itraconazole–Succinic Acid Cocrystals by Gas Antisolvent Cocrystallization, AAPS Pharm Sci Tech. 2012; 13(4):1396–1406.
Ning L, Binghui D, Xianming L, Minghui X, Qian Z, Bozhou W, Preparation of CL-20/DNDAP cocrystals by a rapid and continuous spray drying method: an alternative to cocrystal formation, crystengcomm, 2018.
Amjad A, Waseem K, Graham B, Hardyal G, Ali N, Sitaram P. Theophylline Cocrystals Prepared by Spray Drying: Physicochemical Properties and Aerosolization Performance, AAPS Pharm Sci Tech, 2013; 14(1).
Basavoju S, Bostrom D, Velaga SP. Indomethacin-saccharin co-crystal: Design, synthesis and preliminary pharmaceutical characterization. Pharm Res 2008; 25:530-541.,
Lu J, Rohani S. Preparation and characterization of theophylline − nicotinamide cocrystal. Org Process Res Dev, Article ASAP; 2009.
Zoghbi A., Wang B. Carvedilol solubility enhancement by inclusion complexation and solid dispersion: review. Journal of Drug Delivery and Therapeutics, 2015; 5(2):1-8.
Wenger M, Bernstein J. An alternate crystal form of gabapentin: A cocrystal with oxalic acid. Cryst Growth Des 2008; 8:1595–1598.
Vogt, FG, Clawson, JS. Strohmeier, M, Edwards, AJ, Solid-State NMR Analysis of Organic Cocrystals and Complexes. Cryst. Growth Des. 2009; 9:921–937.
Pindelska, E.; Sokal, A.; Kolodziejski, W. Pharmaceutical cocrystals, slats and polymorphs: Advanced characterization techniques. Adv. Drug Deliv. Rev. 2017; 1:111–146.
Paudel, A, Raijada D, Rantanen J. Raman spectroscopy in pharmaceutical product design. Adv. Drug Deliv. Rev. 2015; 89: 3–20
Langkilde, F.W. Sjoblom, J. Tekenbergs-Hjelte, L. Mrak, J. Quantitative FT-Raman analysis of two crystal forms of a pharmaceutical compound. J. Pharm. Biomed. Anal. 1997; 15:687–696
Hao Z, Ying Z, Ning Q, Yang C, Linghuan G, Preparation and Characterization of Carbamazepine Cocrystal in Polymer Solution, Pharmaceutics. 2017; 9(54):1-13
Shahram E, Khosro A, Mohammad B, Mohammadreza S. Piroxicam cocrystals with phenolic coformers: preparation, characterization, and dissolution properties Department of and characterized with Pharmaceutical and Food. 2017
Desai H, Rao L, Amin P, Carbamazepine Cocrystals by Solvent Evaporation Technique: Formulation and Characterization Studies American journal of pharmatech research, 2018
Fleischman SG, Kuduva SS, McMahon JA, Moulton B, Walsh RB, Rodriguez-Hornedo N, Zaworotko MJ. Crystal engineering of the composition of pharmaceutical phases. 2. Multiple component crystalline solids involving carbamazepine. Cryst Growth Des. 2003; 3:909-919.
Panzade P, Shendarkar G, Shaikh S, Rathi PB, Pharmaceutical Cocrystal of Piroxicam: Design, Formulation and Evaluation. Advanced Pharmaceutical Bulletin. 2017; 7(3):399-408
Bagde S A, Upadhye K P, Dixit G R, Bakhle S S, Formulation and Evaluation of Co-Crystals of Poorly Water Soluble Drug. International Journal of Pharmaceutical Research. 2016; 7(12):4988-4997.
Saxena M, Kuchekar BS, Cocrystal Formulation, Characterization, and Evaluation Study. International Conference on Advanced Nanomaterials & Emerging Engineering technologies" (ICANMEET-20J3) New Deihl, India. 2013; 24(26):602-606
Rajbhar P, Sahu A K, Gautam S S, Prasad R K, Singh V, Nair S K, Formulation and Evaluation of Clarithromycin Co- Crystals Tablets Dosage Forms to Enhance the Bioavailability. The Pharma Innovation. 2016; 5(6):5-13
Latif S, Abbas N, Hussain A, Arshad M S, Bukhari N I, Afjal H, Development of Paracetamol-Caffeine Cocrystals to Improve Compressional, Formulation and In Vivo Performance. 2018; 44(7):1099-1108
Liu M , Hong C , Yao Y , Shen H, Ji G , Li G , Xie Y. Development of a Pharmaceutical Cocrystal With Solution Crystallization Technology: Preparation, Characterization, and Evaluation of Myricetin-Proline Cocrystals. European Journal of Pharmaceutics and Biopharmaceutics. 2016; 107:151-159
Rajurkar V G, Nagare A M, Ghawate V, Tablet Formulation and Enhancement of Aqueous Solubility of Efavirenz by Solvent Evaporation Co-Crystal Technique. Med chem, an open access journal. 2015
Shewale S, Shete A S, Doijad R C, Kadam S S, Patil V A, Yadav A V, Formulation and Solid State Characterization of Nicotinamide-based Co-crystals of Fenofibrate. Indian Journal of Pharmaceutical Sciences. 2015; 77(3):328-334
Hardikar S, Bhosale A, Vanave S, Kamathe B, Preparation and Evaluation OF Co-Crystals of Carbamazepine with Glucomannan. International Journal of Pharmacy and Pharmaceutical Sciences.2017; 9(10):318-320
Childs S L, Kandi P, Lingireddy S R,Formulation of a Danazol Cocrystal with Controlled Supersaturation Plays an Essential Role in Improving Bioavailability. 10:3112−3127
Arafa M F, El-Gizawy S A, Osman MA, & Maghraby GM, Xylitol as a potential co-crystal co-former for enhancing dissolution rate of felodipine: preparation and evaluation of sublingual tablets. Pharmaceutical Development and Technology. 2016
Mounika P, Raj1 V S, Divya1 G, Gowramma A, Vijayamma G, Preparation and Characterization of Novel Co-Crystal Forms of Fexofenadine. International Journal of Innovative Pharmaceutical Research. 2015; 6(1):458-463
Shete A S, Khandagale V V, Murthy M, Yadav A V, Sakhre S S, Doijad R C, Solid State Characterization and Tableting Studies of Ethanol Based Cocrystals of Fenofibrate with Nicotinamide. Indian Journal of Pharmaceutical Education and Research. 2018; 51(2):71-77
Gaikwad E R, Khabade S S, Sutar T B, Payghan S A, Preparation and Characterization of Molecular Complexes of Fenofibrate Cocrystal. Asian Journal of Pharmaceutics. 2017; 11(4):S745-S759
Sopyan I, Fudholi A, Muchtaridi M, Puspita Sari I, Simvastatin-nicotinamide co-crystal: design, preparation and preliminary characterization. Tropical Journal of Pharmaceutical Research. 2017; 16(2):297-303
Tamkhane V V, Design and Development of Prulifloxacin Formulations by Co-Crystallization Technique. International Journal of Pharma Sciences and Research. 2015; 6(8):1146-1155
Ullah M, Ullah H, Murtaza G, Qaisar Mahmood Q, Hussain I, Evaluation of Influence of Various Polymers on Dissolution and Phase Behavior of Carbamazepine-Succinic Acid Cocrystal in Matrix Tablets. BioMed Research International
Patel D M, Shah H R, Patel R J, Patel C, Preparation and Characterization Of Lornoxicam Co-Crystals. World Journal of Pharmacy and Pharmaceutical Sciences. 2014; 3(6):713-732
Kharisma R M, Sopyan I, Dissolution Rate Repairing of Simvastatin as A New Approach in Cocrystallization. Der Pharmacia Lettre. 2017; 9(6):18-27
Mamatha T, Sama M, Queshi H K, Development and evaluation of Mesalamine- Glutamine Cocrystal Tablets for Colon Specific Delivery. 2017; 10(5):3866-3874
Lin Y, Yang H, Yang C, Wang J, Preparation, Characterization, and Evaluation of Dipfluzine–Benzoic Acid Cocrystals with Improved Physicochemical Properties. 2013; 31(3):566-578
Sopyan I, Fudholi A, Muchtaridi M, Puspitasari I, A Novel of Cocrystalization to Improve Solubility and Dissolution rate of Simvastatin. International Journal of PharmTech Research. 2016; 9(6):483-491
Chadha R, Rani D, Goyal P, Novel Cocrystals of Gliclazide: Characterization and Evaluation. Crystengcomm. 1-19
Gadade DD, Pekamwar SS, Shirsat MD, Crystal Engineering of Antiviral Agent Efavirenz for Solubility Enhancement. Journal of Drug Delivery and Therapeutics. 2018; 8(1):86-91
Savjani JK, Pathak C, Improvement of Physicochemical Parameters of Acyclovir using Cocrystallization Approach. Brazilian Journal of Pharmaceutical Sciences. 2016; 52(4):727-734
Thenge RR, Patond V B, Adhao VS, Ajmire PV, Barde LN, Mahajan N M, Tekade N P, Preparation and Characterization of Co-Crystals of Diacerein. 2017; 28(1):34-41
Chadha K, Karan K, Bhalla Y, Chadha R, Khullar S, Mandal S, Vasisht K, Cocrystals of Hesperetin: Structural, Pharmacokinetic, and Pharmacodynamic Evaluation. Crystal Growth & Design. 2017; 17(5): 2386-2405
Vaghela R, Kulkarni PK, Hani U, Varma VNSK, Raizaday A, Enhancing Aqueous Solubility of Ketoprofen by Fusion Technique Using Suitable Co-formers. Current Drug Therapy. 2014; 9(3):199 - 207
Aitipamula S, Wong ABH, Kanaujia P, Evaluating Suspension Formulations of Theophylline Cocrystals with Artificial Sweeteners. Journal of Pharmaceutical Sciences. 2017;1-30
Shete AS, Yadav AV, Murthy MS, Evaluation of performance of co crystals of mefloquine hydrochloride in tablet dosage form. Drug Development and Industrial Pharmacy Informa Health care. 2013; 39(5):716–723
Published
Abstract Display: 4500
PDF Downloads: 3511 How to Cite
Issue
Section
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0). that allows others to share the work with an acknowledgment of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).

.