Optimized Ciclopirox-Based Eudragit RLPO Nail Lacquer: Effect of Endopeptidase Enzyme as Permeation Enhancer on Transungual Drug Delivery and Efficiency Against Onychomycosis
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The aims of our investigation were to develop and optimize ciclopirox (CPX) nail lacquer using nonbiodegradable Eudragit RLPO (E-RLPO) as a film former and to assess its penetration efficiency across the human nail plate. Preliminary trials such as hydration enhancement factor (HEF), a retained drug in the nail plate, and SEM were studied to select the optimized permeation enhancer to be incorporated in the optimized lacquer formulation. A 33 full factorial design was built up to study the effect of three different factors, concentration of E-RLPO (10, 20, and 30%), Tween 80 (0.25, 0.5, and 1%), and triacetin (0, 10, and 30% of polymer weight). The studied responses were the drying time, water resistance, viscosity, and drug release up to 4 h. An ex vivo permeation study for the optimized formulations was carried out. The preliminary study aided the selection of 5% papain (endopeptidase enzyme) as a penetration enhancer; it showed the highest HEF of 15.27%, the highest amount of drug retained in the nail plate (886.2 μg/g). An ex vivo permeation study guided the selection of F4B (flux value of 3.79 μg/cm2/h) as optimized formulation. The optimized lacquer formula showed threefold increases in the permeation than the marketed CPX lacquer (Batrafen®). Confocal laser scanning microscopy revealed the higher intensity of the Rhodamine B dye across the nail plate in the case of the formula containing papain than the marketed formula without papain. Conclusively, an efficient and stable nail lacquer was developed for potential transungual delivery of CPX to target the drug to the nail bed and ensure efficiency against onychomycosis.
Key Wordsciclopirox nail lacquer transungual delivery confocal laser spectroscopy papain
The authors are thankful to Röhm GMbH Chemische Fabrik, Germany, for providing the gift sample of E-RLPO. The authors would like also to acknowledge the National Organization for Drug Control and Research for providing all necessary facilities during project work.
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no conflict of interest.
- 3.Indr Š, Vitalis B. Effect of film-forming polymers on release of naftifine hydrochloride from nail lacquers. Int J Polym Sci. 2017;2017:1–7.Google Scholar
- 6.Westerberg DP, Voyack MJ. Onychomycosis: current trends in diagnosis and management. Am Fam Physician (Review). 2013;88(11):762–70.Google Scholar
- 11.Rajendra VB, Baro A, Kumari A, Dhamecha DL, Lahoti SR, Shelke SD. Transungual drug delivery: an overview. J Appl Pharm Sci. 2012;2(1):203–9.Google Scholar
- 13.Saner MV, Kulkarni AD, Pardeshi CV. Insights into drug delivery across the nail plate barrier. J DrugTargtet. 2014;22(9):769–89.Google Scholar
- 19.Shireesh KR, Chandra SB, Vishnu P, Prasad MV. Ungual drug delivery systems of ketoconazole nail lacquer. Int J Appl Pharm. 2010;2:17–9.Google Scholar
- 20.Crawford F, Hollis S. Topical treatments for fungal infections of the skin and nails of the foot. Cochrane Database Syst Rev 2007, Issue 3. Art. No.: CD001434. doi: https://doi.org/10.1002/14651858.CD001434.pub2.
- 22.Monika J, Vijay S, Kamla P. Matrix based system of isotretinoin as nail lacquer to enhance transungual delivery across human nail plate. Int J Pharm. 2014;478(1):268–77.Google Scholar
- 23.Noha IE, Rehab NS, Ghada A. Terbinafine hydrochloride trans-ungual delivery via nanovesicular systems: in vitro characterization and ex vivo evaluation. AAPS PharmSciTech. 2016;18(2):551–61.Google Scholar
- 24.Gardner HA. Physical examination of paints, varnishes, lacquers and colors. Bethesda: Gardner Laboratory, Inc.; 1956.Google Scholar
- 25.Noha MZ, Gehanne AA, Nahed DM, Seham SA. Enhanced bioavailability of metoclopramide HCl by intranasal administration of a mucoadhesivein situ gel with modulated rheological and mucociliary transport properties. Eur J Pharm Biopharm. 2007;32:296–307.Google Scholar
- 26.Biji P, David BL. A novel transungual formulation (nail patch) for delivery of ciclopirox olamine into the nail and the nail folds. Int J pharm Med Biol Sci. 2014;3(2):152–64.Google Scholar
- 31.Bhagat S, Agarwal M, Roy V. Serratiopeptidase: a systematic review of the existing evidence. In J Surg. 2010;11:209–17.Google Scholar
- 34.Nida A, Hemlata S, Kamla P. Onychomycosis: potential of nail lacquers in transungual delivery of antifungals. Scientifica. 2016;2016:1–12.Google Scholar
- 36.Rajan RS, Jasmina K, Arunabha N. Studies on the effect of plasticizer on in vitro release and ex vivo permeation from Eudragit E 100 based chlorpheniramine maleate matrix type transdermal delivery system. J Excipients Food Chem. 2010;1(2):1–12.Google Scholar
- 37.Schlossman M. Techniques for evaluation of nail enamel. J Soc Cosmet Chem. 1981;32:43–52.Google Scholar
- 38.Sharma PP. Cosmetics—formulation, manufacturing and quality control. 2008; 4th edition Vandana publications (India) Pvt. Ltd., New Delhi.Google Scholar
- 39.Sinko PJ. Physical pharmacy and pharmaceutical sciences. 5th ed. New Delhi: Wolters Kluwer (India) Pvt. Ltd; 2006.Google Scholar
- 41.ASTM (2016) D3924-16, standard specification for standard environment for conditioning and testing paint varnish lacquer, and related materials, Varnish, ASTM International, West Conshohocken, PA, www.astm.org.
- 44.Balsam MS, Edward S. Nail lacquer and remover. In: Balsam MS, Sagarine E, Strianse J, Gershon SD, Rieger MM, editors. Cosmetic science and technology. 2nd edition. Wiley-Interscience, a division of John Wiley and Sons Inc, New York; (1972) Volume 2, chapter (29): p. 521–541.Google Scholar
- 52.Quaddir MA, Reza MS, Haider SS. Effect of polyethylene glycols on release of diclofenac sodium from directly compressed carnauba wax matrix tablets. J Bang Acad Sci. 2002;26(1):1–8.Google Scholar
- 54.Ye Z, Rombout P, Remon JP, Vervaet C, Van den Mooter G. Correlation between the permeability of metoprolol tartrate through plasticized isolated ethylcellulose/hydroxypropyl methylcellulose films and drug release from reservoir pellets. Eur J Pharm Biopharm. 2007;67:485–90.CrossRefPubMedGoogle Scholar
- 58.22Seattone MF, Perini G, Rijli P, Rodriguez L, Cini M. Effect of different polymer-plasticizer combinations on in vitro release of theophylline from coated pellets. Int J Pharm. 1995;126:83–8.Google Scholar