Microwave-Assisted Synthesis: A Green Chemistry Approach for Drug Cocrystals Synthesis

Oktavia Eka Puspita, Melanny Ika Sulistyowaty, Rudy Salam, Dwi Setyawan

Abstract

Microwave-assisted synthesis (MAS) presents a promising approach to the formation of pharmaceutical cocrystals, offering notable improvements in solubility, dissolution rate, stability, and bioavailability of active pharmaceutical ingredients (APIs). This review aims to evaluate the potential of MAS as a green and efficient strategy for drug cocrystal synthesis, particularly in comparison to conventional methods such as solvent evaporation, slurry crystallisation, and grinding techniques. A systematic literature review was conducted following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, to ensure a comprehensive selection of relevant studies. The analysis focused on reported synthesis methods, cocrystal formation under microwave exposure, reaction conditions, yields, purity, and scalability outcomes of MAS compared to conventional techniques. This review also highlight current applications, critical synthesis parameters, and challenges such as penetration depth, reaction uniformity, and thermal control. Findings indicate that MAS significantly reduces reaction time, minimizes solvent use, and enhances product purity and yield. Its compatibility with solvent-free or minimal-solvent processes aligns closely with green chemistry principles, making it a sustainable alternative. Furthermore, MAS effectively addresses solubility mismatches and process inefficiencies commonly encountered in traditional methods. The future prospect of MAS lies in its integration with continuous manufacturing, automation, and drug repurposing efforts, which could revolutionize pharmaceutical formulation by accelerating innovation while adhering to environmental and regulatory standards.

References

Adepu, S. and S. Ramakrishna (2021). Controlled Drug Delivery Systems: Current Status and Future Directions. Molecules, 26; 5905

Ahmad, S., R. Jaiswal, R. Yadav, and S. Verma (2024). Recent Advances in Green Chemistry Approaches for Pharmaceutical Synthesis. Sustainable Chemistry One World, 4; 100029

Ahuja, D., K. A. Ramisetty, P. K. Sumanth, and N. R. Katari (2020). Microwave Assisted Slurry Conversion Crystallization for Manufacturing of New Co-Crystals of Sulfamethazine and Sulfamerazine. CrystEngComm, 22; 1381–1394

Aitipamula, S., R. Banerjee, A. K. Bansal, K. Biradha, M. L. Cheney, A. R. Choudhury, G. R. Desiraju, A. G. Dikundwar, R. Dubey, N. K. Duggirala, P. P. Ghogale, S. Ghosh, S. Goswami, R. Goyal, S. Jain, R. K. R. Jetti, P. Karpinski, D. Kaushik, D. Kumar, V. Kumar, M. Lahoti, A. Nangia, V. Puri, A. Ramanan, T. Rajamannar, K. V. R. Rao, P. Sanphui, N. Shan, G. Shete, A. Singh, C. C. Sun, S. Tothadi, V. R. Vangala, N. Variankaval, P. Vishweshwar, and M. J. Zaworotko (2012). Polymorphs, Salts, and Cocrystals: What’s in a Name? Crystal Growth & Design, 12; 2147–2152

Albuquerque, H. M. T., D. C. G. A. Pinto, and A. M. S. Silva (2021). Microwave Irradiation: Alternative Heating Process for the Synthesis of Biologically Applicable Chromones, Quinolones, and Their Precursors. Molecules, 26; 6293

Alvani, A. and A. Shayanfar (2022). Solution Stability of Pharmaceutical Cocrystals. Crystal Growth & Design, 22; 6323–6337

An, J., X. Dai, Y. Liu, and M. Chen (2025). Design and Process Optimization of a New Reaction Chamber for Microwave Synthesis of MOFs Materials. Heliyon, 11; e41304

Anandam, S. and S. Selvamuthukumar (2014). Optimization of Microwave-Assisted Synthesis of Cyclodextrin Nanosponges Using Response Surface Methodology. Journal of Porous Materials, 21; 1015–1023

Anastas, P. T. and J. C. Warner (2023). Green Chemistry: Theory and Practice. Oxford University Press, Oxford

Antonio, C. and R. T. Deam (2007). Can “Microwave Effects” Be Explained by Enhanced Diffusion? Physical Chemistry Chemical Physics, 9; 2976–2982

Bao, C., A. Serrano-Lotina, and M. Niu (2023). Microwave-Associated Chemistry in Environmental Catalysis for Air Pollution Remediation: A Review. Chemical Engineering Journal, 466; 142902

Baumann, M., T. S. Moody, M. Smyth, and S. Wharry (2020). A Perspective on Continuous Flow Chemistry in the Pharmaceutical Industry. Organic Process Research & Development, 24; 1802–1813

Bavishi, D. D. and C. H. Borkhataria (2016). Spring and Parachute: How Cocrystals Enhance Solubility. Progress in Crystal Growth and Characterization of Materials, 62; 1–8

Bogdal, D. (2005). Microwave Effect vs. Thermal Effect. In Microwave-Assisted Organic Synthesis. Springer, pages 13–21

Bolla, G., B. Sarma, and A. K. Nangia (2022). Crystal Engineering of Pharmaceutical Cocrystals in the Discovery and Development of Improved Drugs. Chemical Reviews, 122; 11514–11603

Chadwick, K., R. Davey, and W. Cross (2007). How Does Grinding Produce Co-Crystals? Insights from the Case of Benzophenone and Diphenylamine. CrystEngComm, 9; 732

Chavan, R. B., R. Thipparaboina, B. Yadav, and N. R. Shastri (2018). Continuous Manufacturing of Co-Crystals: Challenges and Prospects. Drug Delivery and Translational Research, 8; 1726–1739

Dandia, A., S. Bansal, A. Indora, M. Kumari, N. Saini, K. Singh, and V. Rathore (2021). Microwave-Assisted Stereoselective Organic Synthesis. In Green Sustainable Process for Chemical and Environmental Engineering and Science. Elsevier, pages 331–357

de la Hoz, A., A. Diaz-Ortiz, and P. Prieto (2016). Microwave-Assisted Green Organic Synthesis. In Alternative Energy Sources for Green Chemistry. The Royal Society of Chemistry, pages 1–33

Desiraju, G. R. (1995). Supramolecular Synthons in Crystal Engineering—A New Organic Synthesis. Angewandte Chemie International Edition in English, 34; 2311–2327

Desiraju, G. R. (2010). Crystal Engineering: A Brief Overview. Journal of Chemical Sciences, 122; 667–675

Desiraju, G. R. (2013). Crystal Engineering: From Molecule to Crystal. Journal of the American Chemical Society, 135; 9952–9967

Drews, J. and S. Ryser (1996). Innovation Deficit in the Pharmaceutical Industry. Drug Information Journal, 30; 97–108

Ferguson, J. D. (2003). FocusedTM Microwave Instrumentation from CEM Corporation. Molecular Diversity, 7; 281–286

Fischer, F., D. Lubjuhn, S. Greiser, K. Rademann, and F. Emmerling (2016). Supply and Demand in the Ball Mill: Competitive Cocrystal Reactions. Crystal Growth & Design, 16; 5843–5851

Food and Drug Administration, U.S. Department of Health and Human Services (2018). Regulatory Classification of Pharmaceutical Co-Crystals: Guidance for Industry. Technical report

Friščić, T. (2012). Supramolecular Concepts and New Techniques in Mechanochemistry: Cocrystals, Cages, Rotaxanes, Open Metal–Organic Frameworks. Chemical Society Reviews, 41; 3493

Friščić, T. and W. Jones (2009). Recent Advances in Understanding the Mechanism of Cocrystal Formation via Grinding. Crystal Growth & Design, 9; 1621–1637

Friščić, T. and W. Jones (2010). Benefits of Cocrystallisation in Pharmaceutical Materials Science: An Update. Journal of Pharmacy and Pharmacology, 62; 1547–1559

Fuliaş, A., C. Soica, I. Ledeti, and T. Vlase (2014). Characterization of Pharmaceutical Acetylsalicylic Acid–Theophylline Cocrystal Obtained by Slurry Method Under Microwave Irradiation. Revista de Chimie, 11; 1281–1284

Fuliaş, A., G. Vlase, T. Vlase, and I. Ledeti (2015). Screening and Characterization of Cocrystal Formation Between Carbamazepine and Succinic Acid. Journal of Thermal Analysis and Calorimetry, 121; 1081–1086

Gawande, M. B., S. N. Shelke, R. Zboril, and R. S. Varma (2014). Microwave-Assisted Chemistry: Synthetic Applications for Rapid Assembly of Nanomaterials and Organics. Accounts of Chemical Research, 47; 1338–1348

Goyal, H., A. Mehdad, and R. F. Lobo (2020). Scaleup of a Single-Mode Microwave Reactor. Industrial & Engineering Chemistry Research, 59; 2516–2523

Guo, K., G. Sadiq, and C. Seaton (2010). Co-Crystallization in the Caffeine/Maleic Acid System: Lessons from Phase Equilibria. Crystal Growth & Design, 10; 268–273

Guo, M., X. Sun, J. Chen, and T. Cai (2021). Pharmaceutical Cocrystals: A Review of Preparations, Physicochemical Properties and Applications. Acta Pharmaceutica Sinica B, 11; 2537–2564

Guo, Z., W. Han, and W. Zhao (2018). The Effect of Microwave on the Crystallization Process of Magnesium Carbonate from Aqueous Solutions. Powder Technology, 328; 358–366

Harmsen, J. (2010). Process Intensification in the Petrochemicals Industry: Drivers and Hurdles for Commercial Implementation. Chemical Engineering and Processing: Process Intensification, 49; 70–73

Herrero, M. A., J. M. Kremsner, and C. O. Kappe (2008). Nonthermal Microwave Effects Revisited: On the Importance of Internal Temperature Monitoring and Agitation in Microwave Chemistry. Journal of Organic Chemistry, 73; 36–47

Hodgson, J. (2001). ADMET—Turning Chemicals into Drugs. Nature Biotechnology, 19; 722–726

Horikoshi, S., J. M. Catalá-Civera, R. F. Schiffmann, and C. Kanzelberger (2024). Physics of Microwave Heating. In Microwave Chemical and Materials Processing. Springer Nature Singapore, Singapore, pages 95–161

Horikoshi, S., A. Osawa, S. Sakamoto, and N. Serpone (2013). Control of Microwave-Generated Hot Spots. Part IV. Control of Hot Spots on a Heterogeneous Microwave-Absorber Catalyst Surface by a Hybrid Internal/External Heating Method. Chemical Engineering and Processing: Process Intensification, 69; 52–56

Hossain Mithu, M. S., S. A. Ross, A. P. Hurt, and D. Douroumis (2021). Effect of Mechanochemical Grinding Conditions on the Formation of Pharmaceutical Cocrystals and Co-Amorphous Solid Forms of Ketoconazole – Dicarboxylic Acid. Journal of Drug Delivery Science and Technology, 63; 102508

Huang, K., X. Yang, and H. Zhu (2021). Interaction Between Microwave and Molecules. In Dynamics in Microwave Chemistry. Springer Singapore, Singapore, pages 105–149

Huang, N. and N. Rodríguez-Hornedo (2011). Engineering Cocrystal Solubility, Stability, and pHmax by Micellar Solubilization. Journal of Pharmaceutical Sciences, 100; 5219–5234

Huang, Y., L. Zhou, W. Yang, and T. Penulis] (2019). Preparation of Theophylline-Benzoic Acid Cocrystal and On-Line Monitoring of Cocrystallization Process in Solution by Raman Spectroscopy. Crystals, 9; 329

Ioniţă, S., M. Pătraşcu, E. M. Soare, and T. Penulis] (2024). Rapid Synthesis and Evaluation of Resveratrol-Piperazine Cocrystals by Ultrasound and Microwave Methods. Pharmaceutical Research, 41; 1843–1853

Jayasankar, A., A. Somwangthanaroj, Z. J. Shao, and N. Rodríguez-Hornedo (2006). Cocrystal Formation During Cogrinding and Storage Is Mediated by Amorphous Phase. Pharmaceutical Research, 23; 2381–2392

Jeon, S., J. Kim, and D. Yang (2022). Design of Large-Scale Microwave Cavity for Uniform and Efficient Plastic Heating. Polymers, 14; 541

Joshi, M. and A. Roy Choudhury (2018). Salts of Amoxapine with Improved Solubility for Enhanced Pharmaceutical Applicability. ACS Omega, 3; 2406–2416

Kalepu, S. and V. Nekkanti (2015). Insoluble Drug Delivery Strategies: Review of Recent Advances and Business Prospects. Acta Pharmaceutica Sinica B, 5; 442–453

Kalinke, I., P. Kubbutat, and S. Taghian Dinani (2022). Critical Assessment of Methods for Measurement of Temperature Profiles and Heat Load History in Microwave Heating Processes—A Review. Comprehensive Reviews in Food Science and Food Safety, 21; 2118–2148

Kang, Y., J. Gu, and X. Hu (2017). Syntheses, Structure Characterization and Dissolution of Two Novel Cocrystals of Febuxostat. Journal of Molecular Structure, 1130; 480–486

Kappe, C. O. (2004). Controlled Microwave Heating in Modern Organic Synthesis. Angewandte Chemie International Edition, 43; 6250–6284

Kappe, C. O., B. Pieber, and D. Dallinger (2013). Microwave Effects in Organic Synthesis: Myth or Reality? Angewandte Chemie International Edition, 52; 1088–1094

Kappe, C. O. and A. Stadler (2005). Microwaves in Organic and Medicinal Chemistry. In R. Mannhold, H. Kubinyi, and G. Folkers, editors, Microwaves in Organic and Medicinal Chemistry. WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

Karimi-Jafari, M., L. Padrela, G. M. Walker, and D. M. Croker (2018). Creating Cocrystals: A Review of Pharmaceutical Cocrystal Preparation Routes and Applications. Crystal Growth & Design, 18; 6370–6387

Karki, S., T. Friščić, W. Jones, and W. D. S. Motherwell (2007). Screening for Pharmaceutical Cocrystal Hydrates via Neat and Liquid-Assisted Grinding. Molecular Pharmaceutics, 4; 347–354

Kelly, A. L., T. Gough, and R. S. Dhumal (2012). Monitoring Ibuprofen–Nicotinamide Cocrystal Formation During Solvent Free Continuous Cocrystallization (SFCC) Using Near Infrared Spectroscopy as a PAT Tool. International Journal of Pharmaceutics, 426; 15–20

Ketkar, S., S. K. Pagire, and N. R. Goud (2016). Tracing the Architecture of Caffeic Acid Phenethyl Ester Cocrystals: Studies on Crystal Structure, Solubility, and Bioavailability Implications. Crystal Growth & Design, 16; 5710–5716

Kou, Z., Z. Zhao, H. Li, and X. Gao (2023). A Review of Adsorption Intensified by Microwave Irradiation From Absorbent Preparation to Separation Processes. Chemical Engineering and Processing - Process Intensification, 184; 109300

Ku, H. S., E. Siores, A. Taube, and J. A. R. Ball (2002). Productivity Improvement Through the Use of Industrial Microwave Technologies. Computers & Industrial Engineering, 42; 281–290

Kumar, A., Y. Kuang, Z. Liang, and X. Sun (2020). Microwave Chemistry, Recent Advancements, and Eco-Friendly Microwave-Assisted Synthesis of Nanoarchitectures and Their Applications: A Review. Materials Today Nano, 11; 100076

Kuroda, R., K. Higashiguchi, S. Hasebe, and Y. Imai (2004). Crystal to Crystal Transformation in the Solid State. CrystEngComm, 6; 463

Li, S., H. Ma, P. Ouyang, M. Zhang, and Y. Li (2024). Advanced Microwave Synthesis Strategies for Innovative Photocatalyst Design. Green Energy & Environment

Li, Z., K. Peng, N. Ji, and L. Wang (2025). Advanced Mechanisms and Applications of Microwave-Assisted Synthesis of Carbon-Based Materials: A Brief Review. Nanoscale Advances, 7; 419–432

Lidström, P., J. Tierney, B. Wathey, and J. Westman (2001). Microwave Assisted Organic Synthesis—A Review. Tetrahedron, 57; 9225–9283

Lin, H.-L., G.-C. Zhang, Y.-T. Huang, and S.-Y. Lin (2014). An Investigation of Indomethacin–Nicotinamide Cocrystal Formation Induced by Thermal Stress in the Solid or Liquid State. Journal of Pharmaceutical Sciences, 103; 2386–2395

Liu, L., J.-R. Wang, and X. Mei (2022). Enhancing the Stability of Active Pharmaceutical Ingredients by the Cocrystal Strategy. CrystEngComm, 24; 2002–2022

Loftsson, T. and M. E. Brewster (2010). Pharmaceutical Applications of Cyclodextrins: Basic Science and Product Development. Journal of Pharmacy and Pharmacology, 62; 1607–1621

Loupy, A. (2004). Solvent-Free Microwave Organic Synthesis as an Efficient Procedure for Green Chemistry. Comptes Rendus Chimie, 7; 103–112

Makgabutlane, B., L. N. Nthunya, E. N. Nxumalo, and S. D. Mhlanga (2020). Microwave Irradiation-Assisted Synthesis of Zeolites from Coal Fly Ash: An Optimization Study for a Sustainable and Efficient Production Process. ACS Omega, 5; 25000–25008

Martina, K., G. Cravotto, and R. S. Varma (2021). Impact of Microwaves on Organic Synthesis and Strategies Toward Flow Processes and Scaling Up. Journal of Organic Chemistry, 86; 13857–13872

Martinengo, B., E. Diamanti, E. Uliassi, and M. L. Bolognesi (2024). Harnessing the 12 Green Chemistry Principles for Sustainable Antiparasitic Drugs: Toward the One Health Approach. ACS Infectious Diseases, 10; 1856–1870

McNamara, D. P., S. L. Childs, J. Giordano, A. Iarriccio, S. Cassidy, M. S. Shet, R. Mannion, E. O’Donnell, and A. Park (2006). Use of a Glutaric Acid Cocrystal to Improve Oral Bioavailability of a Low Solubility API. Pharmaceutical Research, 23; 1888–1897

Medina, C., D. Daurio, K. Nagapudi, and F. Alvarez-Nunez (2010). Manufacture of Pharmaceutical Co-Crystals Using Twin Screw Extrusion: A Solvent-Less and Scalable Process. Journal of Pharmaceutical Sciences, 99; 1693–1696

Meloni, E., G. Iervolino, and V. Palma (2023). Basics of Microwave Heating and Recent Advances. In Advances in Microwave-Assisted Heterogeneous Catalysis. Royal Society of Chemistry, pages 1–24

Mishra, A., T. Vats, and J. H. Clark (2015). Microwave-Assisted Polymerization. The Royal Society of Chemistry

Miyako, Y., N. Khalef, K. Matsuzaki, and R. Pinal (2010). Solubility Enhancement of Hydrophobic Compounds by Cosolvents: Role of Solute Hydrophobicity on the Solubilization Effect. International Journal of Pharmaceutics, 393; 48–54

Modani, S., A. Gunnam, B. Yadav, A. Rai, P. Arora, P. Dalvi, V. Gaikwad, A. Deogaonkar, S. Chaudhari, S. Shaikh, L. Kankate, A. Sinha, K. Jadhav, and V. Kale (2020). Generation and Evaluation of Pharmacologically Relevant Drug–Drug Cocrystal for Gout Therapy. Crystal Growth & Design, 20; 3577–3583

Mohd Fuad, M. A. H., M. F. Hasan, and F. N. Ani (2019). Microwave Torrefaction for Viable Fuel Production: A Review on Theory, Affecting Factors, Potential and Challenges. Fuel, 253; 512–526

Moradiya, H. G., M. T. Islam, N. Scoutaris, T. Georgiou, P. Chatzitakis, and D. Douroumis (2016). Continuous Manufacturing of High Quality Pharmaceutical Cocrystals Integrated with Process Analytical Tools for In-Line Process Control. Crystal Growth & Design, 16; 3425–3434

Musumeci, D., C. A. Hunter, R. Prohens, S. Scuderi, and J. F. McCabe (2011). Virtual Cocrystal Screening. Chemical Science, 2; 883

Nugrahani, I. and W. N. Auli (2020). Diclofenac–Proline Nano-Co-Crystal Development, Characterization, In Vitro Dissolution and Diffusion Study. Heliyon, 6

Nugrahani, I., D. Utami, L. Ayuningtyas, and Y. Herlina (2019). New Preparation Method Using Microwave, Kinetics, In Vitro Dissolution–Diffusion, and Anti–Inflammatory Study of Diclofenac–Proline Co–Crystal. ChemistrySelect, 4; 13396–13403

Ouyang, J., L. Liu, Y. Li, and Z. Zhou (2024). Cocrystals of Carbamazepine: Structure, Mechanical Properties, Fluorescence Properties, Solubility, and Dissolution Rate. Particuology, 90; 20–30

Page, M. J., J. E. McKenzie, P. M. Bossuyt, I. Boutron, T. C. Hoffmann, C. D. Mulrow, L. Shamseer, J. M. Tetzlaff, E. A. Akl, M. Brennan, R. Chou, J. Glanville, J. M. Grimshaw, A. Hróbjartsson, M. M. Lalu, T. Li, E. W. Loder, E. Mayo-Wilson, S. McDonald, L. A. McGuinness, L. A. Stewart, J. Thomas, A. C. Tricco, V. A. Welch, P. Whiting, and D. Moher (2021). The PRISMA 2020 Statement: An Updated Guideline for Reporting Systematic Reviews. BMJ, 372

Pagire, S., S. Korde, R. Ambardekar, A. Bhosale, A. Dhule, S. Patil, A. Kulkarni, and B. Munjal (2013). Microwave Assisted Synthesis of Caffeine/Maleic Acid Co-Crystals: The Role of the Dielectric and Physicochemical Properties of the Solvent. CrystEngComm, 15; 3705

Pantwalawalkar, J., N. Kale, S. Nangare, S. Mandlik, and P. Pawar (2025). Pharmaceutical Cocrystals: Unlocking the Potential of Challenging Drug Candidates. Journal of Drug Delivery Science and Technology, 104; 106572

Pindelska, E., A. Sokal, and W. Kolodziejski (2017). Pharmaceutical Cocrystals, Salts and Polymorphs: Advanced Characterization Techniques. Advanced Drug Delivery Reviews, 117; 111–146

Priecel, P. and J. A. Lopez-Sanchez (2019). Advantages and Limitations of Microwave Reactors: From Chemical Synthesis to the Catalytic Valorization of Biobased Chemicals. ACS Sustainable Chemistry & Engineering, 7; 3–21

Rong, Y., S. Xue, S. Li, and S. Pang (2023). Study on Preparation of Pillararene Cocrystals by Liquid-Assisted Grinding. Journal of Physics: Conference Series, 2539; 012050

Ross, S. A., A. Ward, P. Basford, E. Turner, and M. Johnson (2024). A Quality by Design Strategy for Cocrystal Design Based on Novel Computational and Experimental Screening Strategies: Part A. Drug Delivery and Translational Research

Sabelström, N., M. Hayashi, T. Watanabe, and K. Nagata (2014). Observation of Localized Heating Phenomena During Microwave Heating of Mixed Powders Using In Situ X-Ray Diffraction Technique. Journal of Applied Physics, 116

Saha, A., A. A. Ahangar, A. A. Dar, M. Prasad, and R. Kumar (2023). Pharmaceutical Cocrystals: A Perspective on Development and Scale-Up of Solution Cocrystallization. Crystal Growth & Design, 23; 7558–7581

Sahoo, B. M. and B. K. Banik (2020). Solvent-Less Reactions: Green and Sustainable Approaches in Medicinal Chemistry. In Green Approaches in Medicinal Chemistry for Sustainable Drug Design. Elsevier, pages 523–548

Serajuddin, A. T. M. (2007). Salt Formation to Improve Drug Solubility. Advanced Drug Delivery Reviews, 59; 603–616

Smith, A. J., P. Kavuru, L. Wojtas, and M. J. Zaworotko (2011). Cocrystals of Quercetin With Improved Solubility and Oral Bioavailability. Molecular Pharmaceutics, 8; 1867–1876

Sulistyowaty, M. I., S. Fitri, N. Yuliati, and A. Hartono (2024a). Solubility and Dissolution Improvement of Paramethoxycinnamic Acid (PMCA) Induced by Cocrystal Formation Using Caffeine as a Coformer. Sains Malaysiana, 53; 3445–3454

Sulistyowaty, M. I., D. Setyawan, P. P. M. Prameswari, and R. Handayani (2024b). A Comparison Study Between Green Synthesis of Microwave Irradiation and Solvent Evaporation Methods in the Formation of p-Methoxycinnamic Acid-Succinic Acid Cocrystals. Science and Technology Indonesia, 9; 629–636

Tangjaideborisut, Y., P. Shanmugam, A.-L. T. Zheng, M. Wong, and Y. Lim (2025). Microwave-Assisted Biosynthesis of Quercetin-Stabilized Gold Nanoparticles With Enhanced Antibacterial and Catalytic Properties. ACS Omega

Taylor, C. R. and G. M. Day (2018). Evaluating the Energetic Driving Force for Cocrystal Formation. Crystal Growth & Design, 18; 892–904

Trask, A. V. and W. Jones (2005). Crystal Engineering of Organic Cocrystals by the Solid-State Grinding Approach. In Crystal Engineering of Organic Cocrystals. Springer, pages 41–70

Trask, A. V., W. Motherwell, and W. Jones (2006). Physical Stability Enhancement of Theophylline via Cocrystallization. International Journal of Pharmaceutics, 320; 114–123

Wang, X., J. Zheng, R. Fu, and J. Ma (2011). Effect of Microwave Power and Irradiation Time on the Performance of Pt/C Catalysts Synthesized by Pulse-Microwave Assisted Chemical Reduction. Chinese Journal of Catalysis, 32; 599–605

Wegiel, L. A., Y. Zhao, L. J. Mauer, E. J. Chun, R. Hussain, S. Willis, C. Johnson, B. Carlson, and K. B. Runkle (2014). Curcumin Amorphous Solid Dispersions: The Influence of Intra and Intermolecular Bonding on Physical Stability. Pharmaceutics Development and Technology, 19; 976–986

Weyna, D. R., T. Shattock, P. Vishweshwar, and M. J. Zaworotko (2009). Synthesis and Structural Characterization of Cocrystals and Pharmaceutical Cocrystals: Mechanochemistry vs Slow Evaporation From Solution. Crystal Growth & Design, 9; 1106–1123

Wäppling Raaholt, B. and S. Isaksson (2017). Improving the Heating Uniformity in Microwave Processing. In The Microwave Processing of Foods. Elsevier, pages 381–406

Xochicale-Santana, L., C. C. Vidyasagar, B. M. Muñoz-Flores, and V. M. J. Pérez (2021). Microwave Assisted Organic Syntheses (MAOS): The Green Synthetic Method. In Handbook of Greener Synthesis of Nanomaterials and Compounds. Elsevier, pages 491–542

Yadav, A. V., A. S. Shete, A. P. Dabke, and P. V. Kulkarni (2009). Co-Crystals: A Novel Approach to Modify Physicochemical Properties of Active Pharmaceutical Ingredients. Indian Journal of Pharmaceutical Sciences, 71; 359–370

Yan, Y., J.-M. Chen, and T.-B. Lu (2015). Thermodynamics and Preliminary Pharmaceutical Characterization of a Melatonin–Pimelic Acid Cocrystal Prepared by a Melt Crystallization Method. CrystEngComm, 17; 612–620

Zeng, F., D. Wang, Y. Tian, Y. Zhang, C. Liu, and G. Wang (2021). Nanoemulsion for Improving the Oral Bioavailability of Hesperetin: Formulation Optimization and Absorption Mechanism. Journal of Pharmaceutical Sciences, 110; 2555–2561

Zhang, X. and D. O. Hayward (2006). Applications of Microwave Dielectric Heating in Environment-Related Heterogeneous Gas-Phase Catalytic Systems. Inorganica Chimica Acta, 359; 3421–3433

Zhou, Z., W. Li, W.-J. Sun, H. Hu, M. Zhang, and J. Xu (2016). Resveratrol Cocrystals with Enhanced Solubility and Tabletability. International Journal of Pharmaceutics, 509; 391–399

Authors

Oktavia Eka Puspita
Melanny Ika Sulistyowaty
Rudy Salam
Dwi Setyawan
dwisetyawan-90@ff.unair.ac.id (Primary Contact)
Author Biographies

Oktavia Eka Puspita, Department of Pharmacy, Faculty of Medicine, Universitas Brawijaya, Malang, 65415, Indonesia

1Department of Pharmaceutical Sciences, Faculty of Pharmacy, Universitas Airlangga, Surabaya, 60115, Indonesia

2Department of Pharmacy, Faculty of Medicine, Universitas Brawijaya, Malang, 65415, Indonesia

Melanny Ika Sulistyowaty, Drug Development Research Center, Universitas Airlangga, Surabaya, 60115, Indonesia

1Department of Pharmaceutical Sciences, Faculty of Pharmacy, Universitas Airlangga, Surabaya, 60115, Indonesia

3Drug Development Research Center, Universitas Airlangga, Surabaya, 60115, Indonesia

Rudy Salam, Department of Biophysics and Physical Chemistry, Faculty of Pharmacy, Charles University, Akademika Heyrovského, Hradec Kralove, 1203, 500 05, Czech Republic

2Department of Pharmacy, Faculty of Medicine, Universitas Brawijaya, Malang, 65415, Indonesia

4Department of Biophysics and Physical Chemistry, Faculty of Pharmacy, Charles University, Akademika Heyrovského, Hradec Kralove, 1203, 500 05, Czech Republic

Dwi Setyawan, Department of Pharmaceutical Sciences, Faculty of Pharmacy, Universitas Airlangga, Surabaya, 60115, Indonesia

1Department of Pharmaceutical Sciences, Faculty of Pharmacy, Universitas Airlangga, Surabaya, 60115, Indonesia

5Pharmaceutical Material Engineering and Processing Research Group, Universitas Airlangga, Surabaya, 60115, Indonesia

6Skin and Cosmetic Technology (SCT) Centre of Excellent, Universitas Airlangga, Surabaya, 60115, Indonesia

7Faculty of Advanced Technology and Multidiscipline, Universitas Airlangga, Surabaya, 60115, Indonesia

Puspita, O. E., Sulistyowaty, M. I. ., Salam, R., & Setyawan, D. . (2025). Microwave-Assisted Synthesis: A Green Chemistry Approach for Drug Cocrystals Synthesis. Science and Technology Indonesia, 10(4), 1130–1147. https://doi.org/10.26554/sti.2025.10.4.1130-1147

Article Details

Most read articles by the same author(s)