Development of Levodon Dosage Form with Controlled Release of the Active Substance
DOI:
https://doi.org/10.37134/jsml.vol14.2.14.2026Keywords:
Levofloxacin , polyvinylpyrrolidone, polymeric complex, effervescent tablet, modified release, drug developmentAbstract
Antibacterial therapy remains a cornerstone of modern medicine due to the persistent prevalence of infectious diseases and the growing challenge of antimicrobial resistance. This study reports the comprehensive development of Levodon, a novel effervescent tablet formulation based on a polymeric complex of levofloxacin with polyvinylpyrrolidone (PVP). The formulation was designed to provide controlled release of the active pharmaceutical ingredient, thereby enhancing the therapeutic efficacy of antibacterial treatment. Preclinical in vivo investigations demonstrated significant dose-dependent antibacterial activity of the developed complex. The formulation and manufacturing process of high-dose effervescent tablets (1110 mg) were successfully optimized. Quality evaluation confirmed that the finished dosage form complied with the requirements of the State Pharmacopoeia of the Republic of Uzbekistan for key pharmaceutical parameters, including identity, disintegration, hardness, and assay. In vitro biopharmaceutical studies revealed a prolonged release profile of levofloxacin across media with varying pH conditions, indicating sustained drug release characteristics. Toxicological assessment further demonstrated that the formulation possesses low acute toxicity (LD₅₀ > 5000 mg/kg) and weak cumulative properties. These findings suggest that Levodon is a promising controlled-release antibacterial dosage form with potential therapeutic advantages in the management of infectious diseases.
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Abrekova NN, Mahmudov SD, Beknazarova NS, Turaboev SM, Sagdullaev BT. (2022). Synthesis and study of the antibacterial activity of polyvinylpyrrolidone polymeric complexes with levofloxacin. International Journal of Materials Chemistry, 12(1), 14-19. doi:10.5923/j.ijmc.20221201.03
Awofisayo SO, Akwaowoh E, Taiwo I, Edem PJ, Awofisayo S. (2025). Optimizing levofloxacin delivery using nanoparticles: a strategy for improved bioavailability and targeted release. Journal of Drug Delivery and Therapeutics, 15(5), 42-49. doi:10.22270/jddt.v15i5.7119
Azhar MAM, Salleh WMNHW. (2020). Chemical composition and biological activities of essential oils of the genus Litsea (Lauraceae) - A review. Agriculturae Conspectus Scientificus, 85(2), 97-103.
Battu H, Prasad MH, Lokesh S, Reenu Y, Pravallika P, Ganesh D, Angel MM. (2025). A review on recent trends of 3D printing technology and its approaches in current drug delivery. Journal of Science and Mathematics Letters, 13(1), 70-98. doi:10.37134/jsml.vol13.1.8.2025
Beknazarova NS, Abrekova NN, Turaboev SM, Ergasheva SM, Sagdullaev BT. (2021). Study of the pharmaceutical and technological parameters of the substance “Sulfapect”. In: Proceedings of the V International Scientific and Practical Conference. Kharkiv, p. 227.
Biswas R, Kapat P, Ghosh A, Sarkhel S, Sarkar T, Das D. (2025). Pharmaceutical polymers in drug delivery: an overview. International Journal of Pharmacy and Pharmaceutical Sciences, 17(7), 1-8. doi:10.22159/ijpps.2025v17i7.54498
Bozal Palabiyik B, Uslu B, Ozkan Y, Ozkan SA. (2018). In vitro drug dissolution studies in medicinal compounds. Current Medicinal Chemistry, 25(33), 4020-4036. doi:10.2174/0929867325666180322145335
Croom KF, Goa KL. (2003). Levofloxacin: a review of its use in the treatment of bacterial infections in the United States. Drugs. 63(24), 2769-2802. doi:10.2165/00003495-200363240-00008
Directive 2010/63/EU of the European Parliament and of the Council on the protection of animals used for scientific purposes. (2010). Official Journal of the European Union, L276, p. 33-79. doi:10.1017/s0962728600010319
Dixit R, Riviere J, Krishnan K, Andersen ME. (2003). Toxicokinetics and physiologically based toxicokinetics in toxicology and risk assessment. Journal of Toxicology and Environmental Health Part B, 6(1), 1-40. doi:10.1080/10937400306479
European Directorate for the Quality of Medicines & HealthCare. European Pharmacopoeia, 7th ed.; Council of Europe: Strasbourg, France, 2010.
Franco P, De Marco I. (2020). The use of poly(N-vinyl pyrrolidone) in the delivery of drugs: a review. Polymers, 12(5), 1114. doi:10.3390/polym12051114
Frimodt-Moller N. (1993). The mouse peritonitis model: present and future use. Journal of Antimicrobial Chemotherapy, 31, 55-60. doi:10.1093/jac/31.suppl_d.55
Hartung T. (2010). Comparative analysis of the revised Directive 2010/63/EU for the protection of laboratory animals with its predecessor 86/609/EEC - a t4 report. Altex, 27(4), 285-303. doi:10.14573/altex.2010.4.285
Heigoldt U, Sommer F, Daniels R, Wagner KG. (2010). Predicting in vivo absorption behavior of oral modified release dosage forms. European Journal of Pharmaceutics and Biopharmaceutics, 76(1), 105-111. doi:10.1016/j.ejpb.2010.05.006
Higuchi T. (1963). Mechanism of sustained-action medication. Theoretical analysis of rate of release of solid drugs dispersed in solid matrices. Journal of Pharmaceutical Sciences, 52(12), 1145-1149. doi:10.1002/jps.2600521210
Izadi E, Afshan G, Patel RP, Rao VM, Liew KB, Meor Mohd Affandi MMR, Kifli N, Suleiman A, Lee KS, Sarker MMR, Zaidi ST, Ming LC. (2019). Levofloxacin: insights into antibiotic resistance and product quality. Journal of Pharmaceutical Policy and Practice, 10, 881. doi:10.3389/fphar.2019.00881
Kadajji VG, Betageri GV. (2011). Water-soluble polymers for pharmaceutical applications. Polymers, 3(4), 1972-2009. doi:10.3390/polym3041972
Kadir NHA, Salleh WMNHW, Ghani NA. (2022). A systematic review on essential oils and biological activities of the genus Syzygium (Myrtaceae). Rivista Italiana delle Sostanze Grasse, 99(2), 165-178.
Karnwal A, Jassim AY, Mohammed AA, Al-Tawaha ARMS, Selvaraj M, Malik T. (2025). Addressing the global challenge of bacterial drug resistance: insights, strategies, and future directions. Frontiers in Microbiology, 16, 1517772. doi:10.3389/fmicb.2025.1517772
Koeppe MO, Cristofoletti R, Fernandes EF, Storpirtis S, Junginger HE, Kopp S, Midha KK, Shah VP, Stavchansky S, Dressman JB, Barends DM. (2011). Biowaiver monographs for immediate-release solid oral dosage forms: levofloxacin. Journal of Pharmaceutical Sciences, 100(5), 1628-1636. doi:10.1002/jps.22405
Korsmeyer RW, Gurny R, Doelker E, Buri P, Peppas NA. (1983). Mechanisms of solute release from porous hydrophilic polymers. International Journal of Pharmaceutics, 15(1), 25-35. doi:10.1016/0378-5173(83)90064-9
Kurakula M, Rao GSNK. (2020). Pharmaceutical assessment of polyvinylpyrrolidone (PVP): As excipient from conventional to controlled delivery systems with a spotlight on COVID-19 inhibition. Journal of Drug Delivery Science and Technology, 60, 102046. doi:10.1016/j.jddst.2020.102046
Li W, Picard F. (2023). Toxicokinetics in preclinical drug development of small molecule new chemical entities. Biomedical Chromatography, 37(7), e5553. doi:10.1002/bmc.5553
Lu H, Cai Z, Hu P. (2024). Recent advances in polymeric delivery vehicles for controlled and sustained drug release. Pharmaceutics, 16(9), 1184. doi:10.3390/pharmaceutics16091184
Luo Y, Hong Y, Shen L, Wu F, Lin X. (2021). Multifunctional role of polyvinylpyrrolidone (PVP) in pharmaceutical formulations. AAPS PharmSciTech, 22(1), 34. doi:10.1208/s12249-020-01909-4
Ramirez M, Pérez-Colmenares A, Obregón-Díaz Y, Rojas-Fermín L, Cordero Y, De Lima W. (2024). Antibacterial and antioxidant activities of fruits of Solanum hirtum Vahl. from Venezuela. Journal of Science and Mathematics Letters, 12(1), 102-110. doi:10.37134/jsml.vol12.1.12.2024
Reza N, Dubey V, Sharland M, Hope W. (2025). Antimicrobial use and resistance. BMJ, 391, e082681. doi:10.1136/bmj.e082681
Rodvold KA, Neuhauser M. (2001). Pharmacokinetics and pharmacodynamics of fluoroquinolones. Pharmacotherapy, 21(10), 233-252. doi:10.1592/phco.21.16.233S.33992
Sadahira T, Wada K, Ikawa K, Morikawa N, Kurahashi H, Yoshioka T, Ariyoshi Y, Kobayashi Y, Araki M, Ishii A, Watanabe M, Uehara S, Watanabe T, Nasu Y. (2017). Clinical pharmacokinetics of oral levofloxacin and sitafloxacin in epididymal tissue. Journal of Infection and Chemotherapy, 23(4), 214-217. doi:10.1016/j.jiac.2016.12.010
Salihu AS, Salleh WMNHW, Ogunwa TH. (2024). Chemical composition, acetylcholinesterase inhibition and molecular docking studies of essential oil from Knema hookeriana Warb. (Myristicaceae). Natural Product Research, 38(14), 2516-2521. doi:10.1080/14786419.2023.2184359
Salleh WMNHW, Ahmad F, Khong HY. (2015). Chemical constituents from Piper caninum and antibacterial activity. Journal of Applied Pharmaceutical Science, 5(6), 20-25. doi:10.7324/JAPS.2015.50604
Sandberg A, Hessler JH, Skov RL, Blom J, Frimodt-Moller N. (2009). Intracellular activity of antibiotics against Staphylococcus aureus in a mouse peritonitis model. Antimicrobial Agents and Chemotherapy, 53(5), 1874-1883. doi:10.1128/AAC.01605-07
Schoofs GM, Willhite CC. (1984). A probit analysis program for the personal computer. Journal of Applied Toxicology, 4(3), 141-144. doi:10.1002/jat.2550040305
Shi Y, Gao P, Gong Y, Ping H. (2010). Application of a biphasic test for characterization of in vitro drug release. Molecular Pharmaceutics, 7(5), 1458-1465. doi:10.1021/mp100114a
Stallard N, Whitehead A. (2004). A statistical evaluation of the fixed dose procedure. Alternatives to Laboratory Animals, 32, 13-21. doi:10.1177/026119290403202s05
State Pharmacopoeia of the Republic of Uzbekistan, 1st ed.; Ministry of Health of the Republic of Uzbekistan, Tashkent, Uzbekistan, 2021.
State Pharmacopoeia of the Russian Federation, 13th ed.; Ministry of Health of the Russian Federation, Moscow, Russia, 2015.
Ter Horst JP, Turimella SL, Metsers F, Zwiers A. (2021). Implementation of quality by design (QbD) principles in regulatory dossiers of medicinal products in the european union (EU) between 2014 and 2019. Therapeutic Innovation & Regulatory Science, 55(3), 583-590. doi:10.1007/s43441-020-00254-9
United States Pharmacopeia and National Formulary (USP 38–NF 33), United States Pharmacopeial Convention: Rockville, MD, USA, 2015.
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Copyright (c) 2026 Beknazarova Nuriya Seytbaevna, Mardikulova Dilshoda Khamrokulovna, Tagayalieva Nigora Abdunabievna, Makhmudov Sardor Djalilovich, Nurmukhamedova Vazira Zaxiritdinovna, Rasulov Alisher Khayotovich, Nabiev Abdusamat Khamidovich, Ziyaev Khayrulla Lutfullaevich, Kholbekov Omonkul Khudoyarovich, Ibragimov Abdurahmon Safievich, Rakhmonova Gulnora Gulomovna, Sagdullaev Bakhodir Takhirovich
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