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Sakshi Tomar
Sapna Rani
Navneet Kaur
Manisha Chopra


Anti-osteoarthritis, Solubility, Dissolution: Eutectics, Coformers


The current research focuses on enhancing the biopharmaceutical characteristics of the anti-osteoarthritic drug etodolac (ET) through the creation of a new solid form. This was achieved by using mechanochemical synthesis to combine ET with coformers that possess antioxidant properties (syringic acid, ascorbic acid, and nicotinic acid), resulting in the formation of three eutectic mixtures (EMs). Differential scanning calorimetry confirmed the formation of these eutectic mixtures, while the exact 50/50% w/w stoichiometry was determined through phase diagrams and Tamman's triangle. The interaction between the components and steric hindrances played a crucial role in eutectic formation. The EMs exhibited significantly increased apparent solubility (between five- to nine-fold) and a notable improvement in intrinsic dissolution rate (two- to three-fold) compared to the original drug. As a result, these solid forms of ET hold promise as viable multicomponent alternatives for further development as therapeutically effective products in the treatment of osteoarthritis.

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1. Balakrishnan I, Venkatachalam S, Datta D, Jawahar N. A brief review on eutectic mixture and its role in pharmaceutical field. International Journal of Research in Pharmaceutical Sciences. 2020.
2. Khadka P, Ro J, Kim HH, Kim I, Kim JT, Kim HH, et al. 4. Solubility and Dissolution Enhancement of Gliclazide. Int J Pharm Chem Anal. 2015;
3. Rajbongshi T, Kumar Sarmah K, Ganduri R, Cherukuvada S, Arhangelskis M, Thakuria R. Mechanosynthesis of Eutectics of Anti‐Inflammatory Drug Ethenzamide – A Comparison with Analogous Cocrystals. Chemistry–Methods. 2021;
4. Al-Akayleh F, Adwan S, Khanfar M, Idkaidek N, Al-Remawi M. Correction to: A Novel Eutectic-Based Transdermal Delivery System for Risperidone (AAPS PharmSciTech, (2021), 22, 1, (4), 10.1208/s12249-020-01844-4). AAPS PharmSciTech. 2021.
5. Allen KD, Thoma LM, Golightly YM. Epidemiology of osteoarthritis. Osteoarthr Cartil. 2021;
6. Berenbaum F. Osteoarthritis as an inflammatory disease (osteoarthritis is not osteoarthrosis!). Osteoarthritis and Cartilage. 2013.
7. Šléglová O. Pain treatment options for osteoarthritis. Vnitr Lek. 2023;
8. Duerinckx J, Verstreken F. Total joint replacement for osteoarthritis of the carpometacarpal joint of the thumb: Why and how? EFORT Open Rev. 2022;
9. Sherje AP, Kulkarni V, Murahari M, Nayak UY, Bhat P, Suvarna V, et al. Inclusion complexation of etodolac with hydroxypropyl-beta-cyclodextrin and auxiliary agents: Formulation characterization and molecular modeling studies. Mol Pharm. 2017;
10. P. Ahirrao S, Sonawane MP, Bhambere DS, Udavant PB, D. Ahire E, Kanade R, et al. Cocrystal Formulation: A Novel Approach to Enhance Solubility and Dissolution of Etodolac. Biosci Biotechnol Res Asia. 2022;
11. Haneef J, Chadha R. Antioxidant-Based Eutectics of Irbesartan: Viable Multicomponent Forms for the Management of Hypertension. AAPS PharmSciTech. 2018;
12. Tomar S, Chakraborti S, Jindal A, Grewal MK, Chadha R. Cocrystals of diacerein: Towards the development of improved biopharmaceutical parameters. Int J Pharm. 2020;
13. Patel RD, Raval MK. Formulation of Diacerein Cocrystal Using β-Resorcylic Acid for Improvement of Physicomechanical and Biopharmaceutical Properties. Org Process Res Dev. 2021;
14. Burchard R, Huflage H, Soost C, Richter O, Bouillon B, Graw JA. Efficiency of platelet-rich plasma therapy in knee osteoarthritis does not depend on level of cartilage damage. J Orthop Surg Res. 2019;
15. De Souza FZR, De Almeida AC, Ferreira PO, Fernandes RP, Caires FJ. Screening of coformers for quercetin cocrystals through mechanochemical methods. Eclet Quim. 2022;
16. Pathak P, Shrivastava K, Ichikawa T, Jain A, Singh R. Pseudo-Binary Phase diagram of LiNH2‐MH (M = Na, K) Eutectic Mixture. Molecules. 2022;
17. Pankov V. Phase composition and phase equilibrium diagrams as the Evidence of the Colloidal State of melts. E3S Web Conf. 2023;
18. Chantel J, Jing Z, Xu M, Yu T, Wang Y. Pressure Dependence of the Liquidus and Solidus Temperatures in the Fe-P Binary System Determined by In Situ Ultrasonics: Implications to the Solidification of Fe-P Liquids in Planetary Cores. J Geophys Res Planets. 2018;
19. Wilhelm-Romero K, Quirós-Fallas MI, Vega-Baudrit JR, Guillén-Girón T, Vargas-Huertas F, Navarro-Hoyos M, et al. Evaluation of Piperine as Natural Coformer for Eutectics Preparation of Drugs Used in the Treatment of Cardiovascular Diseases. AAPS PharmSciTech. 2022;
20. Butreddy A, Almutairi M, Komanduri N, Bandari S, Zhang F, Repka MA. Multicomponent crystalline solid forms of aripiprazole produced via hot melt extrusion techniques: An exploratory study. J Drug Deliv Sci Technol. 2021;