Development and Optimization of a Luliconazole Film-Forming Topical Spray Using a Quality by Design Approach

Luliconazole is a topical antifungal agent used in the management of superficial fungal infections. Film-forming topical sprays may provide convenient application and facilitate the formation of a uniform drug-containing film at the site of administration. The present study aimed to develop and optimize a Luliconazole film-forming spray using a Quality by Design (QbD) approach. A (2^3) full factorial design was employed to investigate the effects of Hydroxypropyl Cellulose (HPC), Eudragit® RS100, and PEG 400 on critical formulation responses, with drying time and viscosity selected as dependent variables. Eight formulations (F1–F8) were prepared by varying the concentrations of the selected formulation components and evaluated for appearance, film formation, pH, viscosity, drying time, spray angle, film thickness, folding endurance, stickiness, washability, leak test, drug content, and in vitro drug diffusion. Statistical analysis and response-surface methodology were used for formulation optimization. The prepared formulations were clear and homogeneous and exhibited acceptable film-forming properties. Drying time ranged from 3.8 to 8.2 min, while viscosity ranged from 162 to 438 cP. The formulation variables significantly influenced the investigated responses. Formulation F8, containing 1% w/v HPC, 4% w/v Eudragit® RS100, and 5% v/v PEG 400, was selected as the optimized formulation. F8 exhibited a drying time of 5.1 min, viscosity of 304 cP, and spray angle of 83.6°. It produced a uniform, transparent, non-sticky, and adherent film, with drug content of 99.2 ± 0.8%. The QbD approach enabled systematic optimization of the Luliconazole film-forming spray and identified F8 as a promising formulation with desirable spray and film-forming characteristics for topical drug delivery.

1. 01.

   1. Shi G, Guo Y, Yang M. Development and optimization of a novel nanocarrier SabiWhite-loaded ethosomal gel for targeted skin inflammation complicated by multidrug-resistant pathogens. Front Cell Infect Microbiol. 2025;15. doi: 10.3389/fcimb.2025.1640799.

   DOI: 10.3389/fcimb.2025.1640799 Google Scholar
2. 02.

   2. Zhu Z, Li W, Yin Y, Cao R, Li Z. Differential Scanning Calorimetry Material Studies: Benzil Melting Point Method for Eliminating the Thermal History of DSC. Vol. 2022, Journal of Chemistry. 2022. doi: 10.1155/2022/3423429.

   DOI: 10.1155/2022/3423429 Google Scholar
3. 03.

   3. Shaligram PS, George CP, Sharma H, Mahadik KR, Patil S, Vanka K, et al. Rivaroxaban eutectics with improved solubility, dissolution rates, bioavailability and stability. CrystEngComm. 2023;25(22):3253–63. doi: 10.1039/d3ce00261f.

   DOI: 10.1039/d3ce00261f Google Scholar
4. 04.

   4. Liaqat R, Rasool F, Noreen S, Rai N, Naseem A, Shoaib MH, et al. Fabrication, characterization, and docking studies of furosemide-loaded nanosponges using the emulsion solvent diffusion method. Nanomedicine. 2025;20(11):1235–47. doi: 10.1080/17435889.2025.2501518.

   DOI: 10.1080/17435889.2025.2501518 Google Scholar
5. 05.

   5. Chaudhari Rn, L.Khan S, Chaudhary Rs, Jain Sp, Sidduqui Fa. Β-Sitosterol: Isolation From Muntingia Calabura Linn Bark Extract, Structural Elucidation And Molecular Docking Studies As Potential Inhibitor Of SARS-CoV-2 Mpro (COVID-19). Asian J Pharm Clin Res. 2020;204–9. doi: 10.22159/ajpcr.2020.v13i5.37909.

   DOI: 10.22159/ajpcr.2020.v13i5.37909 Google Scholar
6. 06.

   6. Alhabardi SA, Almutairi JA, Al-Hamoud GA, Zakaraya ZZ, Hani U, Asiri ZAA, et al. Musa Paradisiaca derived intrinsically heteroatom doped carbon dots as antioxidant and controlled drug release behavior. PLoS One. 2025;1–19. doi: 10.1371/journal.pone.0329116.

   DOI: 10.1371/journal.pone.0329116 Google Scholar
7. 07.

   7. Pham DT, Nguyen DXT, Nguyen NY, Nguyen TTL, Nguyen TQC, Tu AVT, et al. Development of pH-responsive Eudragit S100-functionalized silk fibroin nanoparticles as a prospective drug delivery system. PLoS One. 2024;19(5 May). doi: 10.1371/journal.pone.0303177.

   DOI: 10.1371/journal.pone.0303177 Google Scholar
8. 08.

   8. Patil VP, Khulb P. Isolation and Identification of Bioactive Chlorogenic Acid from Ethanol Fraction of Cordia subcordata: HPLC, HPTLC, FTIR, and LC-MS Analysis. Int J Pharm Qual Assur. 2024;15(03):1144–50. doi: 10.25258/ijpqa.15.3.07.

   DOI: 10.25258/ijpqa.15.3.07 Google Scholar
9. 09.

   9. Vanitha A, Kalimuthu K, Chinnadurai V, Nisha KMJ. Phytochemical screening, FTIR and GCMS analysis of aqueous extract of Caralluma bicolor – An endangered plant. Asian J Pharm Pharmacol. 2019;5(6):1122–30. doi: 10.31024/ajpp.2019.5.6.7.

   DOI: 10.31024/ajpp.2019.5.6.7 Google Scholar
10. 10.

    10. Huang Y, Liu Y, Tan H, Cheng Y, Tao K, Gu D, et al. Assessing essential oil composition in Cinnamomum cassia leaves from different regions of China using GC-MS and FTIR spectroscopy. Czech J Food Sci. 2024;42(3):141–52. doi: 10.17221/197/2023-CJFS.

    DOI: 10.17221/197/2023-CJFS Google Scholar
11. 11.

    11. Dezani AB, Pereira TM, Caffaro AM, Reis JM, Serra CH dos R. Equilibrium solubility versus intrinsic dissolution: Characterization of lamivudine, stavudine and zidovudine for BCS classification. Brazilian J Pharm Sci. 2013;49(4):853–63. doi: 10.1590/S1984-82502013000400026.

    DOI: 10.1590/S1984-82502013000400026 Google Scholar
12. 12.

    12. Romdhani A, Martínez F, Chiappetta DA, Peña Á, Jouyban A. Equilibrium Solubility of Acetaminophen in Ternary Mixtures as a Tool for Design of Concentrated Parenteral Medications. J Solution Chem. 2024;53(3):506–23. doi: 10.1007/s10953-023-01347-3.

    DOI: 10.1007/s10953-023-01347-3 Google Scholar
13. 13.

    13. Ramadoss K, Meerasa SS, Satyapal AKS, Vijayakumar A, Venugopal V. Quantitative analysis of favipiravir in bulk and pharmaceutical dosage forms using UV visible spectrophotometer. J Med Pharm Allied Sci. 2023;12(2):5680–3. doi: 10.55522/jmpas.v12i2.4410.

    DOI: 10.55522/jmpas.v12i2.4410 Google Scholar
14. 14.

    14. Tayeng D, Das S, Das S, Chetia D. UV Spectrophotometric Method Development And Validation For The Combined Plant Extract Traditionally Used In Arunachal Pradesh To Treat Malaria. J Neonatal Surg. 2025;14(30S):975–83. doi: 10.63682/jns.v14i30S.7533.

    DOI: 10.63682/jns.v14i30S.7533 Google Scholar
15. 15.

    15. Sawant MP, Deokar GS. Solubility Profiling and UV-Spectrophotometric Determination of Bioactive Peptides from Ragi. Int J Drug Deliv Technol. 2025;15(3):1265–71. doi: 10.25258/ijddt.15.3.47.

    DOI: 10.25258/ijddt.15.3.47 Google Scholar
16. 16.

    16. N V, SK AP, Yadala PC, M S. UV spectrophotometric method for the estimation of pure nicotine. J Innov Appl Pharm Sci. 2025;37–45. doi: 10.37022/jiaps.v10i3.766.

    DOI: 10.37022/jiaps.v10i3.766 Google Scholar
17. 17.

    17. Fernández-Pérez A, Marbán G. Visible Light Spectroscopic Analysis of Methylene Blue in Water. J Appl Spectrosc. 2022;88(6):1284–90. doi: 10.1021/acsomega.0c03830.

    DOI: 10.1021/acsomega.0c03830 Google Scholar
18. 18.

    18. Azadeh M, Gorovits B, Kamerud J, MacMannis S, Safavi A, Sailstad J, et al. Calibration Curves in Quantitative Ligand Binding Assays: Recommendations and Best Practices for Preparation, Design, and Editing of Calibration Curves. AAPS J. 2018;20(1). doi: 10.1208/s12248-017-0159-4.

    DOI: 10.1208/s12248-017-0159-4 Google Scholar
19. 19.

    19. Kumatia EK, Ofosu-Koranteng F, Appiah AA, Barimah KB. Standardization and Quality Control of the Herbal Medicine Mist Nibima, Employed to Treat Malaria and COVID-19, Using Physicochemical and Organoleptic Parameters and Quantification of Chemical Markers via UHPLC-MS/MS. Int J Anal Chem. 2021;2021. doi: 10.1155/2021/6390481.

    DOI: 10.1155/2021/6390481 Google Scholar
20. 20.

    20. Adebowale ARA, Sanni LO. Effects of solid content and temperature on viscosity of tapioca meal. J Food Sci Technol. 2013;50(3):573–8. doi: 10.1007/s13197-011-0363-7.

    DOI: 10.1007/s13197-011-0363-7 Google Scholar
21. 21.

    21. Ajith K, Pillai AS, Muthu Vijayan Enoch I V., Sharifpur M, Solomon AB, Meyer JP. Effect of the non-electrically conductive spindle on the viscosity measurements of nanofluids subjected to the magnetic field. Colloids Surfaces A Physicochem Eng Asp. 2021;628. doi: 10.1016/j.colsurfa.2021.127252.

    DOI: 10.1016/j.colsurfa.2021.127252 Google Scholar
22. 22.

    22. Zhu W, Long J, Shi M. Release Kinetics Model Fitting of Drugs with Different Structures from Viscose Fabric. Materials (Basel). 2023;16(8). doi: 10.3390/ma16083282.

    DOI: 10.3390/ma16083282 Google Scholar
23. 23.

    23. Askarizadeh M, Esfandiari N, Honarvar B, Sajadian SA, Azdarpour A. Kinetic Modeling to Explain the Release of Medicine from Drug Delivery Systems. ChemBioEng Rev. 2023;10(6):1006–49. doi: 10.1002/cben.202300027.

    DOI: 10.1002/cben.202300027 Google Scholar
24. 24.

    24. Baishya H. Application of Mathematical Models in Drug Release Kinetics of Carbidopa and Levodopa ER Tablets. J Dev Drugs. 2017;06(02). doi: 10.4172/2329-6631.1000171.

    DOI: 10.4172/2329-6631.1000171 Google Scholar
25. 25.

    25. Tembhare E, Gupta KR, Umekar MJ. An Approach to Drug Stability Studies and Shelf-life Determination. Arch Curr Res Int. 2019;1–20. doi: 10.9734/acri/2019/v19i130147.

    DOI: 10.9734/acri/2019/v19i130147 Google Scholar
26. 26.

    26. McKinney E, Deshpande A, Verrilli B, Li C, Sorel D, Kim E, et al. Evaluation of Room Temperature and Accelerated Stability Data For Fitusiran, an Investigational Rnai Therapeutic Targeting Antithrombin for Treatment of Hemophilia and Rare Bleeding Disorders. Haemophilia. 2017;23(S2):59[P051].

    Google Scholar