{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T05:02:22Z","timestamp":1789448542439,"version":"build-2803163510"},"reference-count":57,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:00:00Z","timestamp":1788998400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100015689","name":"Bandung Institute of Technology","doi-asserted-by":"publisher","award":["26D\/IT.1.C10\/SK.KU\/2025"],"award-info":[{"award-number":["26D\/IT.1.C10\/SK.KU\/2025"]}],"id":[{"id":"10.13039\/501100015689","id-type":"DOI","asserted-by":"publisher"}]},{"award":["26D\/IT.1.C10\/SK.KU\/2025"],"award-info":[{"award-number":["26D\/IT.1.C10\/SK.KU\/2025"]}],"id":[{"id":"https:\/\/ror.org\/00apj8t60","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP26K08272"],"award-info":[{"award-number":["JP26K08272"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP24H00005"],"award-info":[{"award-number":["JP24H00005"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"award":["JP26K08272"],"award-info":[{"award-number":["JP26K08272"]}],"id":[{"id":"https:\/\/ror.org\/00hhkn466","id-type":"ROR","asserted-by":"publisher"}]},{"award":["JP24H00005"],"award-info":[{"award-number":["JP24H00005"]}],"id":[{"id":"https:\/\/ror.org\/00hhkn466","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Multicomponent antibiotic\u2013anti-inflammatory systems have recently attracted considerable attention, as this combination is becoming a standard therapy for infectious diseases. This study aimed to develop a multicomponent system comprising norfloxacin (NOR), an old fluoroquinolone antibiotic, and niflumic acid (NIF), another old, poorly soluble anti-inflammatory drug, to improve the physicochemical properties, antibiotic potency, and anti-inflammation effect, as well as their safety. First, a phase diagram was constructed to ensure solid-state reaction and to predict its stoichiometry; subsequently, the multicomponent system was prepared by solvent-drop grinding. The product was analyzed by a series of thermal analyses and powder X-ray diffraction (PXRD). Next, Fourier-transform infrared spectroscopy and nuclear magnetic resonance elucidated the molecular interactions, and the final 3D structure was determined by single-crystal X-ray diffraction, followed by Hirshfeld surface analysis. Afterward, the solubility and chemical stability were assessed using high-performance liquid chromatography, and the physical stability of the multicomponent system was evaluated by PXRD. Antimicrobial potency against Gram-negative and Gram-positive bacteria, as well as anti-inflammatory activity in vivo, were also evaluated. The results demonstrated that a newly formed antibiotic\u2013anti-inflammatory multicomponent system, named norfloxacin\u2013niflumate (NORNIF), in a salt dihydrate form, significantly improved the stability and antibiotic potency of NOR, including against the resistant microbe, as well as the solubility and in vivo anti-inflammatory effect of NIF simultaneously. In addition, preliminary in silico studies using Swiss-ADME and ProTox-3 predicted that the salt was well absorbed in the gastrointestinal tract and could be classified as toxicity class 4 (non-toxic).<\/jats:p>","DOI":"10.3390\/molecules31183189","type":"journal-article","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T13:04:57Z","timestamp":1789045497000},"page":"3189","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Comprehensive Study of a New Norfloxacin-Niflumate Hydrate: Structural and Physicochemical Properties, Antibiotic Potency, Anti-Inflammatory Effect, and Drug Safety"],"prefix":"10.3390","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5069-0343","authenticated-orcid":false,"given":"Ilma","family":"Nugrahani","sequence":"first","affiliation":[{"name":"School of Pharmacy, Bandung Institute of Technology, Bandung 40132, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutong","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Institute of Science Tokyo, Tokyo 152-8551, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia","family":"Fatmawati","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Bandung Institute of Technology, Bandung 40132, Indonesia"},{"name":"Faculty of Pharmacy and Science, Muhammadiyah Prof Dr Hamka University, Jakarta 13460, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9809-1411","authenticated-orcid":false,"given":"Hidehiro","family":"Uekusa","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Institute of Science Tokyo, Tokyo 152-8551, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Risang","family":"Wisesa","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Bandung Institute of Technology, Bandung 40132, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1061-0892","authenticated-orcid":false,"given":"Masaki","family":"Uchida","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Institute of Science Tokyo, Tokyo 152-8551, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marlia Singgih","family":"Wibowo","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Bandung Institute of Technology, Bandung 40132, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.ejps.2016.07.016","article-title":"Solubility, Lipophilicity and Membrane Permeability of Some Fluoroquinolone Antimicrobials","volume":"93","author":"Blokhina","year":"2016","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Hurkacz, M., Dobrek, L., and Wiela-Hoje\u0144ska, A. (2021). Antibiotics and the Nervous System\u2014Which Face of Antibiotic Therapy Is Real, Dr. Jekyll (Neurotoxicity) or Mr. Hyde (Neuroprotection)?. Molecules, 26.","DOI":"10.3390\/molecules26247456"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1111\/imj.12934","article-title":"Spontaneous Bilateral Quadriceps Tendon Rupture Associated with Norfloxacin","volume":"45","author":"Glick","year":"2015","journal-title":"Intern. Med. J."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1715","DOI":"10.1128\/AAC.36.8.1715","article-title":"Photostability and Biological Activity of Fluoroquinolones Substituted at the 8 Position After UV Irradiation","volume":"36","author":"Matsumoto","year":"1992","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_5","first-page":"175","article-title":"The Effect of Photodegradation on the Fluorescent Properties of Norfloxacin","volume":"53","year":"1998","journal-title":"J. Pharm. Belg."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1719","DOI":"10.1039\/C9MD00120D","article-title":"Quinolone Antibiotics","volume":"10","author":"Pham","year":"2019","journal-title":"Medchemcomm"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/j.cjtee.2022.05.002","article-title":"The Combination of Ciprofloxacin and Indomethacin Suppresses the Level of Inflammatory Cytokines Secreted by Macrophages in Vitro","volume":"25","author":"Liu","year":"2022","journal-title":"Chin. J. Traumatol."},{"key":"ref_8","first-page":"365","article-title":"Is A Combination of Antibiotics and Non-Steroidal Anti-Inflammatory Drugs More Beneficial Than Antibiotic Monotherapy for The Treatment of Female Acute Uncomplicated Cystitis? A Randomized Controlled Pilot Study","volume":"15","author":"Ko","year":"2018","journal-title":"Urol. J."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1053\/j.gastro.2017.10.049","article-title":"Mechanisms of Damage to the Gastrointestinal Tract from Nonsteroidal Anti-Inflammatory Drugs","volume":"154","author":"Bjarnason","year":"2018","journal-title":"Gastroenterology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"6420","DOI":"10.1039\/C8CE00900G","article-title":"Multidrug Salt Forms of Norfloxacin with Non-Steroidal Anti-Inflammatory Drugs: Solubility and Membrane Permeability Studies","volume":"20","author":"Bhattacharya","year":"2018","journal-title":"CrystEngComm"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Liang, D., Li, F., Duan, J., Sun, W., and Yu, X. (2024). Two Novel Hydrate Salts of Norfloxacin with Phenolic Acids and Their Physicochemical Properties. Antibiotics, 13.","DOI":"10.3390\/antibiotics13090888"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"122443","DOI":"10.1016\/j.molliq.2023.122443","article-title":"Novel Drug-Drug Salts of Enoxacin with Enhanced Antibacterial Activity: Insights from Solubility and Lipid-Water Partition Coefficient","volume":"385","author":"Li","year":"2023","journal-title":"J. Mol. Liq."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"5311","DOI":"10.2147\/DDDT.S515235","article-title":"Levofloxacin\u2013Niflumate Salt Development as a Strategy for Improving Physicochemical Properties and Modulating Antibiotic Potency and Anti-Inflammatory Performance","volume":"19","author":"Nugrahani","year":"2025","journal-title":"Drug Des. Devel. Ther."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"103779","DOI":"10.1016\/j.xphs.2025.103779","article-title":"Insight on a Novel Drug-Drug Salt Levofloxacin-Flufenamate Crystal Structures, Physicochemical Properties, Potency, and Antiinflammation Improvement","volume":"114","author":"Nugrahani","year":"2025","journal-title":"J. Pharm. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1038\/s41429-024-00759-7","article-title":"Repurposing of Dibucaine and Niflumic Acid as Antimicrobial Agents in Combination with Antibiotics against Staphylococcus Aureus","volume":"77","author":"Chakraborty","year":"2024","journal-title":"J. Antibiot."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Khansari, P.S., and Halliwell, R.F. (2019). Mechanisms Underlying Neuroprotection by the NSAID Mefenamic Acid in an Experimental Model of Stroke. Front. Neurosci., 13.","DOI":"10.3389\/fnins.2019.00064"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Solares-Briones, M., Coyote-Dotor, G., P\u00e1ez-Franco, J.C., Zerme\u00f1o-Ortega, M.R., de la O Contreras, C.M., Canseco-Gonz\u00e1lez, D., Avila-Sorrosa, A., Morales-Morales, D., and Germ\u00e1n-Acacio, J.M. (2021). Mechanochemistry: A Green Approach in the Preparation of Pharmaceutical Cocrystals. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13060790"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"106513","DOI":"10.1016\/j.jct.2021.106513","article-title":"Co-Crystals Formation Specified from Binary Phase Diagram Studies; Their Thermochemical, Spectroscopic and Optical Properties","volume":"161","author":"Neupane","year":"2021","journal-title":"J. Chem. Thermodyn."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1007\/s11095-012-0850-1","article-title":"Detection of Cocrystal Formation Based on Binary Phase Diagrams Using Thermal Analysis","volume":"30","author":"Yamashita","year":"2013","journal-title":"Pharm. Res."},{"key":"ref_20","unstructured":"National Center for Biotechnology Information (2025, February 01). PubChem Compound Summary for CID 4539, Norfloxacin, Available online: https:\/\/pubchem.ncbi.nlm.nih.gov\/compound\/Norfloxacin."},{"key":"ref_21","unstructured":"(2026, August 14). Drugbank Niflumic Acid. Available online: https:\/\/go.drugbank.com\/drugs\/DB04552."},{"key":"ref_22","first-page":"30","article-title":"Organic Nitrogen Compounds V: Amine Salts","volume":"34","author":"Smith","year":"2019","journal-title":"Spectroscopy"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2176","DOI":"10.1021\/om100106e","article-title":"NMR Chemical Shifts of Trace Impurities: Common Laboratory Solvents, Organics, and Gases in Deuterated Solvents Relevant to the Organometallic Chemist","volume":"29","author":"Fulmer","year":"2010","journal-title":"Organometallics"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1107\/S1600576719014092","article-title":"Mercury 4.0: From Visualization to Analysis, Design and Prediction","volume":"53","author":"MacRae","year":"2020","journal-title":"J. Appl. Crystallogr."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.1107\/S1600576721002910","article-title":"CrystalExplorer: A Program for Hirshfeld Surface Analysis, Visualization and Quantitative Analysis of Molecular Crystals","volume":"54","author":"Spackman","year":"2021","journal-title":"J. Appl. Crystallogr."},{"key":"ref_26","first-page":"2807","article-title":"Intensitas Pencahayaan Alami Dan Kenyamanan Visual Untuk Aktivitas Kerja Pada Area Semi-Outdoor Caf\u00e9 di Kota Bandung","volume":"29","author":"Rachel","year":"2024","journal-title":"J. Tek. Sipil Dan Arsit."},{"key":"ref_27","unstructured":"International Conference on Harmonisation (1996, January 6). Technical Requirements for Registration of Pharmaceuticals for Human Use ICH Harmonised Tripartite Guideline Stability Testing. Proceedings of the Photostability Testing of New Drug Substances and Products Q1B, Current Step 4 Version, London, UK."},{"key":"ref_28","unstructured":"International Conference on Harmonisation (2003, January 6). Technical Requirements for Registration of Pharmaceuticals for Human Use ICH Harmonised Tripartite Guideline. Proceedings of the Stability Testing of New Drug Substances and Products Q1A(R2), Tokyo, Japan."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"W257","DOI":"10.1093\/nar\/gky318","article-title":"ProTox-II: A Webserver for the Prediction of Toxicity of Chemicals","volume":"46","author":"Banerjee","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"4524","DOI":"10.1021\/acs.molpharmaceut.4c00429","article-title":"How Does the Powder Mixture of Ibuprofen and Caffeine Attenuate the Solubility of Ibuprofen? Comparative Study for the Xanthine Derivatives to Recognize Their Intermolecular Interactions Using Fourier-Transform Infrared (FTIR) Spectra, Differential Scanning Calorimetry (DSC), and X-Ray Powder Diffractometry (XRPD)","volume":"21","author":"Suenaga","year":"2024","journal-title":"Mol. Pharm."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"135074","DOI":"10.1016\/j.molstruc.2023.135074","article-title":"Structural and Quantitative Analysis of Intermolecular Solid-State Interactions in Cocrystals Obtained from Nucleobases and Methylxanthines with Gallic Acid","volume":"1280","author":"Venkatesan","year":"2023","journal-title":"J. Mol. Struct."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2377","DOI":"10.1002\/1521-3765(20000703)6:13<2377::AID-CHEM2377>3.0.CO;2-L","article-title":"C\uf8ffH-\u03c0 Interactions in 1-n-Butyl-3-Methylimidazolium Tetraphenylborate Molten Salt: Solid and Solution Structures","volume":"6","author":"Dupont","year":"2000","journal-title":"Chem. Eur. J."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"143485","DOI":"10.1016\/j.molstruc.2025.143485","article-title":"Alternatives to Combination Drugs for the Treatment of Septic Arthritis: Preparation of Single Crystals of Flufenamic Acid and Norfloxacin Drug-Drug Salts and Their Physicochemical Properties","volume":"1348","author":"Zhang","year":"2025","journal-title":"J. Mol. Struct."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1039\/D1FD00081K","article-title":"The Role of Solvation in Proton Transfer Reactions: Implications for Predicting Salt\/Co-Crystal Formation Using the \u0394pKa Rule","volume":"235","author":"Lusi","year":"2022","journal-title":"Faraday Discuss."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1448","DOI":"10.1021\/acs.cgd.7b01377","article-title":"Regulation of \u03a0\u00b7\u00b7\u00b7\u03c0 Stacking in Small Molecule Cocrystals and\/or Salts for Physiochemical Modulation","volume":"18","author":"Bora","year":"2018","journal-title":"Cryst. Growth Des."},{"key":"ref_36","first-page":"250","article-title":"H The PH\/Solubility Profile of Norfloxacin","volume":"3","author":"Ahumada","year":"1993","journal-title":"STP Pharma Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1007\/s11095-025-03854-y","article-title":"Correlation Between Dissolution Profiles of Salt-Form Drugs in Biorelevant Bicarbonate Buffer and Oral Drug Absorption: Importance of Dose\/ Fluid Volume Ratio","volume":"42","author":"Tarumi","year":"2025","journal-title":"Pharm. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"61","DOI":"10.5599\/admet.6.1.497","article-title":"Dissolution Rates of Ciprofloxacin and Its Cocrystal with Resorcinol","volume":"6","author":"Fael","year":"2018","journal-title":"ADMET DMPK"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1080\/10408347.2014.941456","article-title":"Review of Properties and Analytical Methods for the Determination of Norfloxacin","volume":"46","author":"Chierentin","year":"2016","journal-title":"Crit. Rev. Anal. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1002\/jps.21165","article-title":"Solid State Interconversion between Anhydrous Norfloxacin and Its Hydrates","volume":"97","author":"Chongcharoen","year":"2008","journal-title":"J. Pharm. Sci."},{"key":"ref_41","unstructured":"International Conference on Harmonisation (1998). Topic Q1B Photostability Testing of New Active Substances and Medicinal Products Step 5 Note for Guidance on The Photostability Testing of New Active Substances and Medicinal Products, European Medicines Agency."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e40373","DOI":"10.1016\/j.heliyon.2024.e40373","article-title":"Solid-State Properties and Antibiotic Potency of Levofloxacin\u2014Dicarboxylate Salts Prepared by the Green Method","volume":"10","author":"Nugrahani","year":"2024","journal-title":"Heliyon"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1021\/acsbiomedchemau.3c00038","article-title":"N4-Substituted Piperazinyl Norfloxacin Derivatives with Broad-Spectrum Activity and Multiple Mechanisms on Gyrase, Topoisomerase IV, and Bacterial Cell Wall Synthesis","volume":"3","author":"Aboraia","year":"2023","journal-title":"ACS Bio Med. Chem. Au"},{"key":"ref_44","unstructured":"(1990). Niflumic Acid Is a Beneficial Adjuvant to Antibacterial Therapy for Tonsillitis. Inpharma Wkly., 733, 15."},{"key":"ref_45","first-page":"4612021","article-title":"Novel Microdilution Method to Assess Double and Triple Antibiotic Combination Therapy in Vitro","volume":"2016","year":"2016","journal-title":"Int. J. Microbiol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"292","DOI":"10.4103\/0253-7613.157127","article-title":"A Study of the Mechanisms Underlying the Anti-Inflammatory Effect of Ellagic Acid in Carrageenan-Induced Paw Edema in Rats","volume":"47","author":"Mansouri","year":"2015","journal-title":"Indian J. Pharmacol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"117899","DOI":"10.1016\/j.bmc.2024.117899","article-title":"Design, Classification, and Adverse Effects of NSAIDs: A Review on Recent Advancements","volume":"112","author":"Arfeen","year":"2024","journal-title":"Bioorg. Med. Chem."},{"key":"ref_48","unstructured":"European Medicines Agency (2018). Disabling and Potentially Permanent Side Effects Lead to Suspension or Restrictions of Quinolone and Fluoroquinolone Antibiotics, European Medicines Agency."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2140","DOI":"10.1021\/ci700257y","article-title":"Computation of Octanol\u2212Water Partition Coefficients by Guiding an Additive Model with Knowledge","volume":"47","author":"Cheng","year":"2007","journal-title":"J. Chem. Inf. Model."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1021\/ci034243x","article-title":"ESOL: Estimating Aqueous Solubility Directly from Molecular Structure","volume":"44","author":"Delaney","year":"2004","journal-title":"J. Chem. Inf. Comput. Sci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1080\/01480545.2023.2240036","article-title":"Long-Term Toxicity of Fluoroquinolones: A Comprehensive Review","volume":"47","author":"Hussen","year":"2024","journal-title":"Drug Chem. Toxicol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1177\/1091581817704379","article-title":"Salt Selection Matters: Differential Renal Toxicity with MDV1634.Maleate Versus MDV1634.2HCl","volume":"36","author":"Guha","year":"2017","journal-title":"Int. J. Toxicol."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Nugrahani, I., Tjengal, B., Gusdinar, T., Horikawa, A., and Uekusa, H. (2020). A Comprehensive Study of a New 1.75 Hydrate of Ciprofloxacin Salicylate: SCXRD Structure Determination, Solid Characterization, Water Stability, Solubility, and Dissolution Study. Crystals, 10.","DOI":"10.3390\/cryst10050349"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Nugrahani, I., Laksana, A.N., Uekusa, H., and Oyama, H. (2022). New Organic Salt from Levofloxacin-Citric Acid: What Is the Impact on the Stability and Antibiotic Potency?. Molecules, 27.","DOI":"10.3390\/molecules27072166"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1107\/S2053229614024218","article-title":"Crystal Structure Refinement with SHELXL","volume":"71","author":"Sheldrick","year":"2015","journal-title":"Cryst. Struct. Commun."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"e31548","DOI":"10.1016\/j.heliyon.2024.e31548","article-title":"Ilma Nugrahani Piperine-Hydroxybenzoate as Phytochemistry Antiosteoarthritis Combination: Structural, Solubility, and in Vivo Antiinflammatory Study","volume":"10","author":"Sartinah","year":"2024","journal-title":"Heliyon"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"17268","DOI":"10.1038\/s41598-023-44557-x","article-title":"The Synthesis, Thermal Behaviour, Spectral and Structural Characterization, and in Silico Prediction of Pharmacokinetic Parameters of Tetraalkylammonium Salts of Non-Steroidal Anti-Inflammatory Drug Nimesulide","volume":"13","author":"Sikorski","year":"2023","journal-title":"Sci. Rep."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/31\/18\/3189\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T04:12:02Z","timestamp":1789445522000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/31\/18\/3189"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,10]]},"references-count":57,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["molecules31183189"],"URL":"https:\/\/doi.org\/10.3390\/molecules31183189","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,10]]}}}