SpringerLink
Log in

Solubility and Dissolution Enhancement of Luliconazole by a Cocrystal Engineering Technique with Different Coformers

  • Original Article
  • Published:
Journal of Pharmaceutical Innovation Aims and scope Submit manuscript

Abstract

Introduction

In this article, we demonstrate the application of cooling crystallization to generate novel solid forms of drug-coformer cocrystal complexes.

Method

This approach enabled us to replicate several cocrystal phases previously reported for pharmaceutical drugs. Additionally, we successfully produced a new solid mixture comprising the drug luliconazole and coformers such as mannitol and menthol, as well as a potential new crystal form of the cocrystal luliconazole:menthol and luliconazole:mannitol. By utilizing cooling crystallization, we were able to prepare phase-pure LCZ-MNT and LCZ-MNL cocrystals.

Result

This study utilized PXRD, thermal methods, and FTIR to analyze cocrystals formed between drug and two coformers, menthol (MNT) and mannitol (MNL). Pure luliconazole showed−345.26 mJ heat of fusion (ΔH) and cocrystals with menthol and mannitol showed−516.19 mJ and−566.46 mJ respectively. The cocrystals showed lower heats of fusion (ΔH) compared to luliconazole, indicating the possibility of increased entropy and solubility for all cocrystals. Both the coformer and drug components showed band shifts in their spectra. A new solid phase was assumed to have formed if the PXRD of the cocrystal product differed from that of the reactants. Pure luliconazole resulted in 6.91 µg/ml solubility and cocrystal with menthol resulted in 26.87 µg/ml solubility. Using cooling crystallization with the menthol coformer resulted in a fivefold increase in cocrystal solubility compared to pure drug. The study also demonstrated improvements in drug dissolution.

Conclusion

The DSC analysis showed that the cooling crystallization method resulted in cocrystals with lower heats of fusion. The results of FTIR studies, the drug, and coformer showed only weak interactions, creating the new solid form. PXRD data indicated that the cooling crystallization method modified the crystal habits. Solubility and dissolution studies revealed that cocrystals of luliconazole could be an effective approach for enhancing its solubility.

Graphical Abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (Germany)

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

Data Availability

The represented data is authentic, objective, and a true depiction of the research study.

References

  1. Scher RK, Nakamura N, Tavakkol A. Luliconazole: a review of a new antifungal agent for the topical treatment of onychomycosis. Mycoses. 2014;57(7):389–93.

    Article  PubMed  CAS  Google Scholar 

  2. Sharma M, Mundlia J, Kumar T, Ahuja M. A novel microwave-assisted synthesis, characterization and evaluation of luliconazole-loaded solid lipid nanoparticles. Polym Bull. 2021;78(5):2553–67.

    Article  CAS  Google Scholar 

  3. Hasan S, Bhandari S, Sharma A. International journal of research publication and reviews formulation and evaluation of luliconazole emulgel [Internet]. Vol. 3, International journal of research publication and reviews. 2022. Available from: http://www.ijrpr.com

  4. Shaikh MS, Kale MA, Shaikh MM, Mahaparale PR. Formulation, characterization and antimicrobial studies of lyophilized luliconazole nanosuspension for enhancing solubility using modified polymer. Int J Polym Mater Polym Biomater. 2022;71(9):692–706.

    Article  CAS  Google Scholar 

  5. Saunders J, Maki K, Koski R, Nybo SE. Tavaborole, Efinaconazole, and luliconazole: three new antimycotic agents for the treatment of dermatophytic fungi. J Pharm Prac. SAGE Publications Inc. 2017;30:621–30.

  6. Sathisaran I, Dalvi SV. Engineering cocrystals of poorlywater-soluble drugs to enhance dissolution in aqueous medium. Pharmaceutics. MDPI AG. 2018;10.

  7. Vimalson DC, Parimalakrishnan S, Jeganathan NS, Anbazhagan S. Techniques to enhance solubility of hydrophobic drugs: an overview. Asian J Pharm. 10.

  8. Savjani KT, Gajjar AK, Savjani JK. Drug solubility: importance and enhancement techniques. ISRN Pharm. 2012;5(2012):1–10.

    Google Scholar 

  9. Siepmann J, Siepmann F. Mathematical modeling of drug dissolution. Int J Pharm. Elsevier B.V. 2013;453:12–24.

  10. Patel DJ, Puranik PK. Pharmaceutical co-crystal : an emerging technique to enhance physicochemical properties of drugs. Int J Chemtech Res. 2020;13(3):283–90.

    Article  CAS  Google Scholar 

  11. Duggirala NK, Frericks Schmidt HL, Lei Z, Zaworotko MJ, Krzyzaniak JF, Arora KK. Solid-state characterization and relative formation enthalpies to evaluate stability of cocrystals of an antidiabetic drug. Mol Pharm. 2018;15(5):1901–8.

    Article  PubMed  CAS  Google Scholar 

  12. Kumar A, Nanda A. In-silico methods of cocrystal screening: a review on tools for rational design of pharmaceutical cocrystals. Vol. 63, Journal of drug delivery science and technology. Editions de Sante; 2021.

  13. Mohite R, Mehta P, Arulmozhi S, Kamble R, Pawar A, Bothiraja C. Synthesis of fisetin co-crystals with caffeine and nicotinamide using the cooling crystallization technique: biopharmaceutical studies. New J Chem. 2019;43(34):13471–9.

    Article  CAS  Google Scholar 

  14. Desai H, Rao L, Amin P. Carbamazepine cocrystals by solvent evaporation technique: formulation and characterisation studies ocular drug delivery for the treatment of glaucoma view project cocrystallization of poorly soluble drugs view project [Internet]. 2014. Available from: http://www.ajptr.com

  15. Karimi-Jafari M, Padrela L, Walker GM, Croker DM. Creating cocrystals: a review of pharmaceutical cocrystal preparation routes and applications. Cryst Growth Des. Am Chem Soc 2018;18:6370–87.

  16. Izutsu KI, Koide T, Takata N, Ikeda Y, Ono M, Inoue M, et al. Characterization and quality control of pharmaceutical cocrystals. Chem Pharm Bull. 64:1421.

  17. Bhanu P, Sundararajan R. Spectrophotometric determination of luliconazole in bulk and pharmaceutical dosage form. Res J Pharm Technol. 2020;13(2):928–32.

    Article  Google Scholar 

  18. Losev E, Boldyreva E. The effect of amino acid backbone length on molecular packing: Crystalline tartrates of glycine, β-alanine, γ-aminobutyric acid (GABA) and dl-α-aminobutyric acid (AABA). Acta Crystallogr C Struct Chem. 2018;74(2):177–85.

    Article  PubMed  CAS  Google Scholar 

  19. Suhail M, Wu PC, Minhas MU. Development and characterization of pH-sensitive chondroitin sulfate-co-poly(acrylic acid) hydrogels for controlled release of diclofenac sodium. J Saudi Chem Soc. 2021;25(4).

  20. Pralhad T, Rajendrakumar K. Study of freeze-dried quercetin-cyclodextrin binary systems by DSC, FT-IR, X-ray diffraction and SEM analysis. J Pharm Biomed Anal. 2004;34(2):333–9.

    Article  PubMed  CAS  Google Scholar 

  21. Arunkumar N, Deecaraman M, Rani C, Mohanraj KP, Venkates Kumar K. Preparation and solid state characterization of atorvastatin nanosuspensions for enhanced solubility and dissolution. Int J Pharmtech Res. CODEN. Vol. 1.

  22. Weng J, Wong SN, Xu X, Xuan B, Wang C, Chen R, et al. Cocrystal Engineering of itraconazole with suberic acid via rotary evaporation and spray drying. Cryst Growth Des. 2019;19(5):2736–45.

    Article  CAS  Google Scholar 

  23. Kumar M, Shanthi N, Kumar Mahato A. Qualitative and quantitative methods for determination of drug luliconazole. International journal of research in advent technology [Internet]. 2018;6(10). Available from: http://www.ijrat.org

  24. Schultheiss N, Newman A. Pharmaceutical cocrystals and their physicochemical properties. Cryst Growth Des. 2009;9:2950–67.

  25. Sugandha K, Kaity S, Mukherjee S, Isaac J, Ghosh A. Solubility enhancement of ezetimibe by a cocrystal engineering technique. Cryst Growth Des. 2014;14(9):4475–86.

    Article  CAS  Google Scholar 

  26. Chatur VM, Dhole SN. Development and characterization of niosomal gel for topical delivery of luliconazole. International journal of pharmaceutical research and allied sciences. 2022;11(1):99–107.

    Article  CAS  Google Scholar 

  27. Al-Akayleh F, Mohammed Ali HH, Ghareeb MM, Al-Remawi M. Therapeutic deep eutectic system of capric acid and menthol: Characterization and pharmaceutical application. J Drug Deliv Sci Technol. 2019;1:53.

    Google Scholar 

  28. Guimarães TF, Lanchote AD, Da Costa JS, Viçosa AL, De Freitas LAP. A multivariate approach applied to quality on particle engineering of spray-dried mannitol. Adv Powder Technol. 2015;26(4):1094–101.

    Article  Google Scholar 

  29. Kumar M, Shanthi N, Mahato AK, Soni S, Rajnikanth PS. Preparation of luliconazole nanocrystals loaded hydrogel for improvement of dissolution and antifungal activity. Heliyon. 2019;5(5): e01688.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

I owe my humble thanks to Bioderma Laboratoire for providing gift sample of luliconazole. I owe my deepest gratitude to Mr. Krupal Shanishchara for continuous support and guidance towards this research project.

Funding

The Department of Technical Education, Government of Gujarat, India, provided the financial assistance (minor research grant) provided under the SSIP (Student Startup & Innovation Policy) scheme and KS Patel Centre for Entrepreneurship, RK University for this project.

Author information

Authors and Affiliations

  1. School of Pharmacy, RK University, Kasturbadham, Rajkot, Gujarat- 360020, India

    Meet Aghara & Kiran Dudhat

Authors
  1. Meet Aghara
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kiran Dudhat
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All the authors have contributed to the research work and preparation of the final manuscript.

Corresponding author

Correspondence to Kiran Dudhat.

Ethics declarations

Ethics Approval

No animal or human subjects were used during the preparation of this manuscript.

Consent for Publication

Nil.

Conflict of Interest

The authors declare no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Aghara, M., Dudhat, K. Solubility and Dissolution Enhancement of Luliconazole by a Cocrystal Engineering Technique with Different Coformers. J Pharm Innov 18, 1701–1712 (2023). https://doi.org/10.1007/s12247-023-09751-4

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12247-023-09751-4

Keywords

Search

Navigation