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image of A Systematic Quality by Design-Based Formulation Study to Develop Optimized Ciprofloxacin Hydrochloride-Loaded Nanoparticles for Controlled Drug Release

Abstract

Introduction

Nanoparticles have been developed to enhance the delivery of

Ciprofloxacin hydrochloride, improve therapeutic efficacy, and address the challenges of

conventional antibiotic therapy, including biofilm penetration and drug resistance. The study aimed to optimize Ciprofloxacin hydrochloride-loaded nanoparticles using Face-Centered

Central Composite Design (FCCCD) within a Quality by Design (QbD) framework, focusing on critical quality attributes (CQA) and critical material attributes (CMA).

Methods

Thirteen experimental batches were prepared using FCCCD with ethyl cellulose

(EC) and Tween 80 as independent variables. The formulations were characterized in terms

of encapsulation efficiency, particle size, and drug release. Optimization was performed using Design Expert software (Stat-Ease 360 trial version) with response surface methodology. The

optimized formulation was validated through four checkpoint batches. Similarity factor analysis and accelerated stability studies were conducted in accordance with ICH guidelines.

Results

The optimized formulation demonstrated an encapsulation efficiency of 74.66 ± 1.01%, a particle size of 83.64 ± 0.23 nm, and a drug release of 77.70 ± 0.53%. Statistical analysis confirmed the significance of the response models (p < 0.05) with high R2 values (0.9930 for encapsulation efficiency, 0.9880 for particle size, and 0.9963 for drug release), validating the predictive capability of the model. The experimental checkpoint batches showed strong agreement between predicted and observed values. Similarity factor analysis (f2 = 60) indicated a close match between the drug release profile of the optimized and reference formulations. Stability studies confirmed the physical and chemical stability of the product over three months.

Discussion

FCCCD effectively optimized Ciprofloxacin hydrochloride nanoparticles by systematically evaluating the impact of EC and Tween 80 on CQA. The use of response surface methodology ensured resource efficiency while identifying an optimal formulation space. The similarity in release profile with the reference formulation and the confirmed stability highlight the clinical relevance of the optimized nanoparticles.

Conclusion

The study demonstrated that FCCCD is a robust and resource-efficient statistical tool for nanoparticle optimization. Ciprofloxacin hydrochloride nanoparticles with high encapsulation efficiency, controlled release, and confirmed stability were successfully developed, offering a cost-effective approach for improved antibiotic delivery.

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2025-12-30
2026-02-24

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References

  1. Ghelich R. Jahannama M.R. Abdizadeh H. Torknik F.S. Vaezi M.R. Central composite design (CCD)-Response surface methodology (RSM) of effective electrospinning parameters on PVP-B-Hf hybrid nanofibrous composites for synthesis of HfB2-based composite nanofibers. Compos., Part B Eng. 2019 166 527 541 10.1016/j.compositesb.2019.01.094
    [Google Scholar]
  2. Sharma1, V.; Chauhan, A.S. Process variable studies for the preparation of optimized drug delivery system using central composite design. Int. J. Drug Develop Res. 2023 15 1 8
    [Google Scholar]
  3. Nazzal S. Khan M.A. Response surface methodology for the optimization of ubiquinone self-nanoemulsified drug delivery system. AAPS PharmSciTech 2002 3 1 23 31 10.1208/pt030103 12916956
    [Google Scholar]
  4. Sharma V. Singh P. Singh L. Verma N. Application of face centered central composite design in evolution of optimized drug delivery system of golden nutraceutical with frame independent variables. Curr. Cosmetic Sci. 2023 2 e160323214669 10.2174/2666779702666230316093558
    [Google Scholar]
  5. Dayal P. Pillay V. Babu R.J. Singh M. Box-Behnken experimental design in the development of a nasal drug delivery system of model drug hydroxyurea: Characterization of viscosity, in vitro drug release, droplet size, and dynamic surface tension. AAPS PharmSciTech 2005 6 4 E573 E585 10.1208/pt060472 16408859
    [Google Scholar]
  6. Beg S. Swain S. Rahman M. Hasnain M.S. Imam S.S. Application of design of experiments (DoE) in pharmaceutical product and process optimization. Pharmaceutical Quality by Design: Principles and Applications. Academic Press 2019 10.1016/B978‑0‑12‑815799‑2.00003‑4
    [Google Scholar]
  7. Maity S. Applications of selected response surface design of experiments and advanced control charts in textile engineering. Textile Calculation. Woodhead Publishing 2023 10.1016/B978‑0‑323‑99041‑7.00015‑1
    [Google Scholar]
  8. Jain A. Hurkat P. Jain S.K. Development of liposomes using formulation by design: Basics to recent advances. Chem. Phys. Lipids 2019 224 104764 10.1016/j.chemphyslip.2019.03.017 30951713
    [Google Scholar]
  9. Bharadwaj A. Rastogi A. Pandey S. Gupta S. Sohal J.S. Multidrug‐resistant bacteria: Their mechanism of action and prophylaxis. BioMed Res. Int. 2022 2022 1 5419874 10.1155/2022/5419874 36105930
    [Google Scholar]
  10. Mithuna R. Tharanyalakshmi R. Jain I. Singhal S. Sikarwar D. Das S. Ranjitha J. Ghosh D. Rahman M.M. Das B. Emergence of antibiotic resistance due to the excessive use of antibiotics in medicines and feed additives: A global scenario with emphasis on the Indian perspective. Emerg. Contam. 2024 10 4 100389 10.1016/j.emcon.2024.100389
    [Google Scholar]
  11. Yayehrad A.T. Wondie G.B. Marew T. Different nanotechnology approaches for ciprofloxacin delivery against multidrug-resistant microbes. Infect. Drug Resist. 2022 15 413 426 10.2147/IDR.S348643 35153493
    [Google Scholar]
  12. Thai T. Salisbury B.H. Zito P.M. Ciprofloxacin. StatPearls. StatPearls Publishing 2023
    [Google Scholar]
  13. Sharma D. Patel R.P. Zaidi S.T.R. Sarker M.M.R. Lean Q.Y. Ming L.C. Interplay of the quality of ciprofloxacin and antibiotic resistance in developing countries. Front. Pharmacol. 2017 8 546 10.3389/fphar.2017.00546 28871228
    [Google Scholar]
  14. Rusu A. Munteanu A.C. Arbănași E.M. Uivarosi V. Overview of side-effects of antibacterial fluoroquinolones: New drugs versus old drugs, a step forward in the safety profile? Pharmaceutics 2023 15 3 804 10.3390/pharmaceutics15030804 36986665
    [Google Scholar]
  15. Omrani N. Nezamzadeh-Ejhieh A. Focus on scavengers’ effects and GC-MASS analysis of photodegradation intermediates of sulfasalazine by Cu2O/CdS nanocomposite. Separ. Purif. Tech. 2020 235 116228 10.1016/j.seppur.2019.116228
    [Google Scholar]
  16. Rahmani-Aliabadi A. Nezamzadeh-Ejhieh A. A visible light FeS/Fe 2 S 3/zeolite photocatalyst towards photodegradation of ciprofloxacin. J. Photochem. Photobiol. Chem. 2018 357 1 10 10.1016/j.jphotochem.2018.02.006
    [Google Scholar]
  17. Ghattavi S. Nezamzadeh-Ejhieh A. GC-MASS detection of methyl orange degradation intermediates by AgBr/g-C3N4: Experimental design, bandgap study, and characterization of the catalyst. Int. J. Hydrogen Energy 2020 45 46 24636 24656 10.1016/j.ijhydene.2020.06.207
    [Google Scholar]
  18. Sobhani Z. Mohammadi Samani S. Montaseri H. Khezri E. Nanoparticles of chitosan loaded Ciprofloxacin: Fabrication and antimicrobial activity. Adv. Pharm. Bull. 2017 7 3 427 432 10.15171/apb.2017.051 29071225
    [Google Scholar]
  19. Page-Clisson M.E. Pinto-Alphandary H. Ourevitch M. Andremont A. Couvreur P. Development of ciprofloxacin-loaded nanoparticles: physicochemical study of the drug carrier. J. Control. Release 1998 56 1-3 23 32 10.1016/S0168‑3659(98)00065‑0 9801426
    [Google Scholar]
  20. Nijhawan H.P. Prabhakar B. Yadav K.S. Central composite design augmented quality-by-design-based systematic formulation of erlotinib hydrochloride-loaded chitosan-poly (lactic-co-glycolic acid) nanoparticles. Ther. Deliv. 2024 15 6 427 447 10.1080/20415990.2024.2342771 38722230
    [Google Scholar]
  21. Ghaemmaghamian Z. Zarghami R. Walker G. O’Reilly E. Ziaee A. Stabilizing vaccines via drying: Quality by design considerations. Adv. Drug Deliv. Rev. 2022 187 114313 10.1016/j.addr.2022.114313 35597307
    [Google Scholar]
  22. Sharma V. Singh L. Jaiswal A. Akhtar M.S. Implementation of quality by design approach for development of optimized drug delivery system of antidepressant drug. Res. J. Pharm. Technol 2024 17 496 500 10.52711/0974‑360X.2024.00077
    [Google Scholar]
  23. Vutpala Sreelola O. Abbaraju, Krishna Sailaja Preparation and characterisation of ibuprofen loaded polymeric nanoparticles by solvent evaporation technique. Int. J. Pharm. Pharm. Sci. 2014 6 8 416 421
    [Google Scholar]
  24. Zhang X.F. Liu Z.G. Shen W. Gurunathan S. Silver nanoparticles: Synthesis, characterization, properties, applications, and therapeutic approaches. Int. J. Mol. Sci. 2016 17 9 1534 10.3390/ijms17091534 27649147
    [Google Scholar]
  25. Singh A. Kumar P. Verma A. Development and optimization of roflumilast-loaded nanostructured lipid carrier (NLCs) formulation for topical delivery. Orient. J. Chem. 2025 41 1 11 24 10.13005/ojc/410102
    [Google Scholar]
  26. Desai M. Godbole A.M. Somnache S. Gajare P. Pednekar A. Manerikar S. Kudaskar K. Naik V. Design, development, and characterization of film forming spray as novel antifungal topical formulation for superficial fungal infections. Indian J. Pharm. Edu Res. 2022 56 4s s651 s658 10.5530/ijper.56.4s.211
    [Google Scholar]
  27. Gohel M.C. Nagori S.A. Fabrication of modified transport fluconazole transdermal spray containing ethyl cellulose and Eudragit RS100 as film formers. AAPS PharmSciTech 2009 10 2 684 691 10.1208/s12249‑009‑9256‑8 19462250
    [Google Scholar]
  28. Sheth T.S. Acharya F. Optimizing similarity factor of in vitro drug release profile for development of early stage formulation of drug using linear regression model. J. Math. Ind. 2021 11 1 9 10.1186/s13362‑021‑00104‑9
    [Google Scholar]
  29. Yadav A. Kumar Tiwari R. Singh L. Significance of hydrophobic polymer in novel drug delivery system. Res. J. Pharm. Technol 2023 16 73 78 10.52711/0974‑360X.2023.00013
    [Google Scholar]
  30. Huang L. Hu W. Yue P. Liao Y. Chen H. Chen Y. Development and evaluation of Tween-80 modified breviscapine nanocrystals for enhanced oral absorption. J. Drug Deliv. Sci. Technol. 2025 107 106819 10.1016/j.jddst.2025.106819
    [Google Scholar]
  31. Alkholief M. Kalam M.A. Anwer M.K. Alshamsan A. Effect of solvents, stabilizers and the concentration of stabilizers on the physical properties of Poly(d,l-lactide-co-glycolide) nanoparticles: Encapsulation, in vitro release of indomethacin and cytotoxicity against HepG2-Cell. Pharmaceutics 2022 14 4 870 10.3390/pharmaceutics14040870 35456705
    [Google Scholar]
  32. Olivera M.E. Manzo R.H. Junginger H.E. Midha K.K. Shah V.P. Stavchansky S. Dressman J.B. Barends D.M. Biowaiver monographs for immediate release solid oral dosage forms: ciprofloxacin hydrochloride. J. Pharm. Sci. 2011 100 1 22 33 10.1002/jps.22259 20602455
    [Google Scholar]
/content/journals/ddl/10.2174/0122103031403695251117184720
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A Systematic Quality by Design-Based Formulation Study to Develop Optimized Ciprofloxacin Hydrochloride-Loaded Nanoparticles for Controlled Drug Release
Bentham Science Publishers ; https://doi.org/10.2174/0122103031403695251117184720
/content/journals/ddl/10.2174/0122103031403695251117184720
/content/journals/ddl/10.2174/0122103031403695251117184720
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  • Article Type:     Research Article
Keywords: quality by design ; Critical quality attributes ; ethyl cellulose ; face centered central composite design ; similarity factor ; tween 80 ; validation check

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