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image of Development, Characterization, In Vitro, Ex Vivo, and Stability Evaluation of a Miconazole Nitrate Nanocrystal-loaded Hydrogel for Topical Application

Abstract

Introduction

This study aimed to develop, characterize, optimize, and evaluate the drug and stability of miconazole nitrate (MN)-loaded nanocrystal for topical drug delivery. MN is an antifungal agent with poor oral bioavailability and significant first-pass metabolism, necessitating alternative administration routes. Nanoformulations with lipidic/polymeric nanoparticles can overcome conventional system formulation limitations. However, it resulted in controlled MN drug release for up to 48 h and greater skin flux than did a 1% MN solution. This study aimed to identify optimized, stable, and effective MN-loaded nanocrystal-based hydrogels for topical drug delivery.

Methods

The nanocrystals (PN1-PN12) were developed the precipitation method using Pluronic F-127 as a nonionic copolymer surfactant and stabilizer. The compatibility was evaluated differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and Fourier transform infrared spectroscopy (FT-IR). With the help of the zetasizer, particle size, PDI, and Zeta Potential are determined. The drug release was determined using the dialysis bag method. Carbopol 934-P and methylparaben were dissolved in distilled water with heat and constant stirring to prevent agglomeration. Permeation experiments used excised abdominal skin from Wistar rats euthanized by cervical dislocation.

Results

The highest solubility was found in PF-127, followed by Pluronic F68. Nanocrystals were prepared the antisolvent precipitation method. The new diffraction pattern of the nanocrystals confirms their crystalline nature and complexation with the polymer, supporting the DSC and FT-IR findings. The developed nanocrystal shows a subtle shift from 1587 to 1589 cm-1, with no significant changes in the vibrational frequencies of the physical mixture. The PN5 formulation, with a small PS of 303.4 nm, a low PDI of 0.248, the highest drug content of 99.23 ± 5.23%, and a % cumulative drug release of 92.32 ± 3.27, was selected for further characterization. The PN5 formulations were stored under various conditions for 3 months, resulting in consistent particle sizes. SEM images revealed long, crystalline MN structures and needle-like nanocrystals. PN5 was optimized for developing a topical nanocrystal gel (PG1), which provided sustained drug release and retained significantly more drug than the other formulations did. PG1 remained stable during the 3-month storage.

Conclusion

The PN5 formulation, optimized for developing a topical nanocrystal gel, resulted in consistent particle size, sustained drug release, and stability over 3 months.

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2025-07-28
2025-08-05

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References

  1. Yeo I.J. Yun J. Son D.J. Han S.B. Hong J.T. Antifungal drug miconazole ameliorated memory deficits in a mouse model of LPS-induced memory loss through targeting iNOS. Cell Death Dis. 2020 11 8 623 10.1038/s41419‑020‑2619‑5 32796824
    [Google Scholar]
  2. Tejada G. Barrera M.G. García P. Sortino M. Lamas M.C. Lassalle V. Alvarez V. Leonardi D. Nanoparticulated systems based on natural polymers loaded with miconazole nitrate and lidocaine for the treatment of topical candidiasis. AAPS PharmSciTech 2020 21 7 278 10.1208/s12249‑020‑01826‑6 33033939
    [Google Scholar]
  3. Al-Maghrabi P.M. Khafagy E.S. Ghorab M.M. Gad S. Influence of formulation variables on miconazole nitrate–loaded lipid based nanocarrier for topical delivery. Colloids Surf. B Biointerfaces 2020 193 111046 10.1016/j.colsurfb.2020.111046 32416518
    [Google Scholar]
  4. Singh S. Patil V.M. Paliwal S.K. Masand N. Nanotechnology-based drug delivery of topical antifungal agents. Pharm. Nanotechnol. 2023 11 10.2174/2211738511666230818125031 37594096
    [Google Scholar]
  5. Rasool M. Mazhar D. Afzal I. Zeb A. Khan S. Ali H. In vitro and in vivo characterization of miconazole nitrate loaded transethosomes for the treatment of cutaneous candidiasis. Int. J. Pharm. 2023 647 123563 10.1016/j.ijpharm.2023.123563 37907141
    [Google Scholar]
  6. Phechkrajang C. Phiphitphibunsuk W. Sukthongchaikool R. Nuchtavorn N. Leanpolchareanchai J. Development of miconazole-loaded microemulsions for enhanced topical delivery and non-destructive analysis by near-infrared spectroscopy. Pharmaceutics 2023 15 6 1637 10.3390/pharmaceutics15061637 37376085
    [Google Scholar]
  7. Ambreen Z. Faran S.A. Daniel A. Khalid S.H. Khan I.U. Asif M. Rehman A. Mehmood H.Q. Asghar S. Physicochemical, rheological and antifungal evaluation of miconazole nitrate organogels for topical delivery. Pak. J. Pharm. Sci. 2022 35 4(Special) 1215 1221 10.36721/PJPS.2022.35.4.SP.1215‑1221.1 36218100
    [Google Scholar]
  8. Farooq U. Rasul A. Zafarullah M. Abbas G. Rasool M. Ali F. Ahmed S. Javaid Z. Abid Z. Riaz H. Mahmood Arshad R.K. Maryam S. Amna N. Asif K. Nanoemulsions as novel nanocarrieres for drug delivery across the skin: In-vitro, in-vivo evaluation of miconazole nanoemulsions for treatment of Candidiasis albicans. Des. Monomers Polym. 2021 24 1 240 258 10.1080/15685551.2021.1965724 34434070
    [Google Scholar]
  9. Bhalekar M.R. Pokharkar V. Madgulkar A. Patil N. Patil N. Preparation and evaluation of miconazole nitrate-loaded solid lipid nanoparticles for topical delivery. AAPS PharmSciTech 2009 10 1 289 296 10.1208/s12249‑009‑9199‑0 19294517
    [Google Scholar]
  10. Asghar Z. Jamshaid T. Sajid-ur-Rehman M. Jamshaid U. Gad H.A. Novel transethosomal gel containing miconazole nitrate; Development, characterization, and enhanced antifungal activity. Pharmaceutics 2023 15 11 2537 10.3390/pharmaceutics15112537 38004517
    [Google Scholar]
  11. Farooq U. Rasul A. Sher M. Qadir M.I. Nazir I. Mehmood Y. Riaz H. Shah P.A. Jamil Q.A. Khan B.A. Development, characterization and evaluation of anti- fungal activity of miconazole based nanogel prepared from biodegradable polymer. Pak. J. Pharm. Sci. 2020 33 1(Special) 449 457 32173643
    [Google Scholar]
  12. Abdel-Rashid R.S. Helal D.A. Alaa-Eldin A.A. Abdel- Monem R. Polymeric versus lipid nanocapsules for miconazole nitrate enhanced topical delivery: In vitro and ex vivo evaluation. Drug Deliv. 2022 29 1 294 304 10.1080/10717544.2022.2026535 35037528
    [Google Scholar]
  13. Baveloni F.G. Riccio B.V.F. Di Filippo L.D. Fernandes M.A. Meneguin A.B. Chorilli M. Nanotechnology-based drug delivery systems as potential for skin application: A review. Curr. Med. Chem. 2021 28 16 3216 3248 10.2174/0929867327666200831125656 32867631
    [Google Scholar]
  14. Sun L. Xiang H. Ge C. Chen X. Zhang Q. Zhang Y. Miao X. A nanocrystals-based topical drug delivery system with improved dermal penetration and enhanced treatment of skin diseases. J. Biomed. Nanotechnol. 2021 17 12 2319 2337 10.1166/jbn.2021.3202 34974856
    [Google Scholar]
  15. Liu Y. Zhao J. Chen J. Miao X. Nanocrystals in cosmetics and cosmeceuticals by topical delivery. Colloids Surf. B Biointerfaces 2023 227 113385 10.1016/j.colsurfb.2023.113385 37270904
    [Google Scholar]
  16. Rahman M. Singh J.G. Afzal O. Altamimi A.S.A. Alrobaian M. Haneef J. Barkat M.A. Almalki W.H. Handa M. Shukla R. Nasar Mir Najib Ullah S. Kumar V. Beg S. Preparation, characterization, and evaluation of curcumin–graphene oxide complex-loaded liposomes against Staphylococcus aureus in topical disease. ACS Omega 2022 7 48 43499 43509 10.1021/acsomega.2c03940 36506117
    [Google Scholar]
  17. Sinha B. Müller R.H. Möschwitzer J.P. Systematic investigation of the cavi-precipitation process for the production of ibuprofen nanocrystals. Int. J. Pharm. 2013 458 2 315 323 10.1016/j.ijpharm.2013.10.025 24148667
    [Google Scholar]
  18. Chang D. Ma Y. Cao G. Wang J. Zhang X. Feng J. Wang W. Improved oral bioavailability for lutein by nanocrystal technology: Formulation development, in vitro and in vivo evaluation. Artif. Cells Nanomed. Biotechnol. 2018 46 5 1018 1024 10.1080/21691401.2017.1358732 28749189
    [Google Scholar]
  19. Chaudhary S. Garg T. Rath G. Murthy R.R. Goyal A.K. Enhancing the bioavailability of mebendazole by integrating the principles solid dispersion and nanocrystal techniques, for safe and effective management of human echinococcosis. Artif. Cells Nanomed. Biotechnol. 2015 44 3 1 6 10.3109/21691401.2014.1000493 25783855
    [Google Scholar]
  20. Mohamed A.R. Abolmagd E. Badrawy M. Nour I.M. Innovative earth-friendly uv-spectrophotometric technique for in vitro dissolution testing of miconazole nitrate and nystatin in their vaginal suppositories: Greenness assessment. J. AOAC Int. 2022 105 6 1528 1535 10.1093/jaoacint/qsac074 35699478
    [Google Scholar]
  21. Hussain A. Begum A. Rahman A. Effects of annealing on nanocrystalline Bi2S3 thin films prepared by chemical bath deposition. Mater. Sci. Semicond. Process. 2014 21 1 74 81 10.1016/j.mssp.2014.01.029
    [Google Scholar]
  22. Jurca T. Józsa L. Suciu R. Pallag A. Marian E. Bácskay I. Mureșan M. Stan R.L. Cevei M. Cioară F. Vicaș L. Fehér P. Formulation of topical dosage forms containing synthetic and natural anti-inflammatory agents for the treatment of rheumatoid arthritis. Molecules 2020 26 1 24 10.3390/molecules26010024 33374575
    [Google Scholar]
  23. Preet S. Kaur J. Raza K. Nisin loaded carbopol gel against Pseudomonas aeruginosa infected third-degree burns: A therapeutic intervention. Wound Repair Regen. 2021 29 5 711 724 10.1111/wrr.12909 33721379
    [Google Scholar]
  24. Scomoroscenco C. Teodorescu M. Raducan A. Stan M. Voicu S.N. Trica B. Ninciuleanu C.M. Nistor C.L. Mihaescu C.I. Petcu C. Cinteza L.O. Novel gel microemulsion as topical drug delivery system for curcumin in dermatocosmetics. Pharmaceutics 2021 13 4 505 10.3390/pharmaceutics13040505 33916981
    [Google Scholar]
  25. Pawar V.K. Gupta S. Singh Y. Meher J.G. Sharma K. Singh P. Gupta A. Bora H.K. Chaurasia M. Chourasia M.K. Pluronic F-127 stabilised docetaxel nanocrystals improve apoptosis by mitochondrial depolarization in breast cancer cells: Pharmacokinetics and toxicity assessment. J. Biomed. Nanotechnol. 2015 11 10 1747 1763 10.1166/jbn.2015.2158 26502638
    [Google Scholar]
  26. Jain S. Reddy V.A. Arora S. Patel K. Development of surface stabilized candesartan cilexetil nanocrystals with enhanced dissolution rate, permeation rate across CaCo-2, and oral bioavailability. Drug Deliv. Transl. Res. 2016 6 5 498 510 10.1007/s13346‑016‑0297‑8 27129488
    [Google Scholar]
  27. Zong R. Ruan H. Zhu W. Zhang P. Feng Z. Liu C. Fan S. Liang H. Li J. Curcumin nanocrystals with tunable surface zeta potential: Preparation, characterization and antibacterial study. J. Drug Deliv. Sci. Technol. 2022 76 103771 10.1016/j.jddst.2022.103771
    [Google Scholar]
  28. Rojek B. Gazda M. Plenis A. FTIR, Raman spectroscopy and HT-XRD in compatibility study between naproxen and excipients. Spectrochim. Acta A Mol. Biomol. Spectrosc. 2023 302 123048 10.1016/j.saa.2023.123048 37354860
    [Google Scholar]
  29. Rossetti A. Real D.A. Barrientos B.A. Allemandi D.A. Paredes A.J. Real J.P. Palma S.D. Significant progress in improving Atorvastatin dissolution rate: Physicochemical characterization and stability assessment of self-dispersible Atorvastatin/Tween 80® nanocrystals formulated through wet milling and freeze-drying. Int. J. Pharm. 2024 650 123720 , 650, 123720 10.1016/j.ijpharm.2023.123720 38110014
    [Google Scholar]
  30. Melian M.E. Paredes A. Munguía B. Colobbio M. Ramos J.C. Teixeira R. Manta E. Palma S. Faccio R. Domínguez L. Nanocrystals of novel valerolactam-fenbendazole hybrid with improved in vitro dissolution performance. AAPS PharmSciTech 2020 21 7 237 10.1208/s12249‑020‑01777‑y 32808055
    [Google Scholar]
  31. Wadhawan J. Parmar P.K. Bansal A.K. Nanocrystals for improved topical delivery of medium soluble drug: A case study of acyclovir. J. Drug Deliv. Sci. Technol. 2021 65 102662 10.1016/j.jddst.2021.102662
    [Google Scholar]
  32. Le Gars M. Roger P. Belgacem N. Bras J. Role of solvent exchange in dispersion of cellulose nanocrystals and their esterification using fatty acids as solvents. Cellulose 2020 27 8 4319 4336 10.1007/s10570‑020‑03101‑0
    [Google Scholar]
  33. Jahangir M.A. Imam S.S. Muheem A. Chettupalli A. Al-Abbasi F.A. Nadeem M.S. Kazmi I. Afzal M. Alshehri S. Nanocrystals: Characterization overview, applications in drug delivery, and their toxicity concerns. J. Pharm Innov. 2022 17 237 248
    [Google Scholar]
  34. Pelikh O. Stahr P.L. Huang J. Gerst M. Scholz P. Dietrich H. Geisel N. Keck C.M. Nanocrystals for improved dermal drug delivery. Eur. J. Pharm. Biopharm. 2018 128 170 178 10.1016/j.ejpb.2018.04.020 29680482
    [Google Scholar]
  35. Mol Pereira E.A. Santos C.S. Biosurfactants as stabilizers of niclosamide nanocrystals: Enhancing stability, solubility, and cytotoxicity profiling. J. Drug Deliv. Sci. Technol. 2024 100 106095 10.1016/j.jddst.2024.106095
    [Google Scholar]
  36. Chen C. Yu G. Zhou Y. Fu H. Huang W. Wang Z. Luo X. Yin X. Mao S. Zhu K. Enhanced stability and dissolution of curcumin nanocrystals stabilized by octenyl succinic anhydride modified starch. J. Drug Deliv. Sci. Technol. 2024 96 105701 10.1016/j.jddst.2024.105701
    [Google Scholar]
  37. Castañeda L. A facile method for formulation of atenolol nanocrystal drug with enhanced bioavailability. Nanocrystalline Materials. Intech Open 2019 1 14 10.5772/intechopen.88191
    [Google Scholar]
  38. Mazumder R. Paul S.D. Formulation and evaluation of atenolol nanocrystals using 3(2) full factorial design. Nanosc. Nanotechnol. Asia. 2020 10 3 306 315
    [Google Scholar]
  39. Kumar A. Valamla B. Thakor P. Chary P.S. Rajana N. Mehra N.K. Development and evaluation of nanocrystals loaded hydrogel for topical application. J. Drug Deliv. Sci. Technol. 2022 74 103503 10.1016/j.jddst.2022.103503
    [Google Scholar]
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Development, Characterization, In Vitro, Ex Vivo, and Stability Evaluation of a Miconazole Nitrate Nanocrystal-loaded Hydrogel for Topical Application
Bentham Science Publishers ; https://doi.org/10.2174/0109298673339390250605054706
/content/journals/cmc/10.2174/0109298673339390250605054706
/content/journals/cmc/10.2174/0109298673339390250605054706
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  • Article Type:     Research Article
Keywords: nanocrystal ; Miconazole nitrate ; in vitro drug release ; zeta potential ; particle size ; stability study ; scanning electron microscopy

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