DESIGNING OF NOVEL TOPICAL IN SITU POLYMERIC FILM-FORMING SOLUTION SPRAY FORMULATION OF ANTIFUNGAL AGENT: IN VITRO ACTIVITY AND IN VIVO CHARACTERIZATION

Authors

  • Nabil Abdullah Department of Pharmaceutics sciences, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Mysuru, 570015, Karnataka, India https://orcid.org/0000-0002-0368-102X
  • Amit B Patil Department of Pharmaceutics sciences, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Mysuru, 570015, Karnataka, India

DOI:

https://doi.org/10.22159/ijap.2022v14i1.43581

Keywords:

In Situ Film, Voriconazole, Candida Albicans, In vitro & In vivo antifungal activity

Abstract

Objective: Voriconazole (VCZ) is a broad-spectrum antifungal medication that works by inhibiting fungal Cytochrome P450, preventing fungi growth. The current study aims at developing and characterizing an antifungal in situ film-forming polymeric solution spray containing VCZ for use in topical drug delivery systems.

Methods: Optimized VCZ in situ polymeric film formulation was evaluated for Fourier transform infrared spectroscopy (FTIR), differential scanning calorimeter (DSC), X-ray diffractometry (XRD), Scanning electron microscope (SEM), in vitro & in vivo, ex-vivo investigation using abdominal rat skin and stability studies. The in-vivo antifungal activity of the advanced in situ film was examined in albino Wistar rats.

Results: The optimized batch contained 22% Eudragit RS 100 (ERS) and 4% Sorbitol. Based on FTIR, XRD, SEM, and rheological studies. Formulation ingredients of VCZ loaded topical in situ polymeric film spray were observed to be compatible and showed no evidence of precipitation, deformation, or discoloration. Diffusion test (in vitro %), and ex-vivo drug diffusion % obtained 99.22%, and 97.45% respectively. The maximum inhibition zone was measured at 13±0.07 mm. The Wistar rat was employed as an animal model for skin irritation and antifungal studies. A study of short-term stability observed no significant modifications in the physical properties.

Conclusions: The findings of the optimized VCZ topical in situ polymeric film spray formulation were satisfactory, demonstrating comparable improvement in superficial antifungal treatment.

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References

Achkar JM, Fries BC. Candida infections of the genitourinary tract. Clinical Microbiology Reviews. 2010;23(2):253–73.

Jackson BE, Wilhelmus KR, Mitchell BM. Genetically regulated filamentation contributes to Candida albicans virulence during corneal infection. Microbial Pathogenesis. 2007;42(2–3):88–93.

Tran TTD, Tran PHL. Controlled Release Film Forming Systems in Drug Delivery: The Potential for Efficient Drug Delivery. Pharmaceutics [Internet]. 2019 Jun 20;11(6):290.

Kim Y, Beck-Broichsitter M, Banga AK. Design and evaluation of a poly(Lactide-co-glycolide)-based in situ film-forming system for topical delivery of trolamine salicylate. Pharmaceutics. 2019;11(8).

Frederiksen K, Guy RH, Petersson K. The potential of polymeric film-forming systems as sustained delivery platforms for topical drugs. Expert Opinion on Drug Delivery [Internet]. 2016 Mar 3;13(3):349–60.

Silva-Alvarez AF, Ferreira MP, Vicentini FTMC, Pedrazzi V, de Freitas O. A New Approach to Ex Vivo Permeation Studies in In-Situ Film-Forming Systems. AAPS PharmSciTech [Internet]. 2020 Oct 7;21(7):257.

Felton LA. Mechanisms of polymeric film formation. International Journal of Pharmaceutics [Internet]. 2013;457(2):423–7.

Umar AK, Butarbutar M, Sriwidodo S, Wathoni N. Film-forming sprays for topical drug delivery. Drug Design, Development and Therapy. 2020;14:2909–25.

Psimadas D, Georgoulias P, Valotassiou V, Loudos G. Impact of Antinucleants on Transdermal Delivery of Testosterone from a Spray. Journal of pharmaceutical sciences. 2012;101(7):2271–80.

Riyaz Ali M. Osmani PKK. 32 Full Factorial Design for Development and Characterization of Nanosponges Based Intravaginal in situ Gelling System for Vulvovaginal Candidiasis. RSC Advances. 2016;11(23).

Fukuda IM, Pinto CFF, Moreira CDS, Saviano AM, Lourenço FR. Design of experiments (DoE) applied to pharmaceutical and analytical quality by design (QbD). Brazilian Journal of Pharmaceutical Sciences. 2018;54(Special Issue):1–16.

Nabil Abdullah, Amit B Patil. Application of DoE in polymers screening and optimization of in situ topical film-forming solution for spray formulation. International Journal of Research in Pharmaceutical Sciences. 2020;11(Special Issue 4):2499–515.

Frederiksen K, Guy RH, Petersson K. Formulation considerations in the design of topical, polymeric film-forming systems for sustained drug delivery to the skin. European Journal of Pharmaceutics and Biopharmaceutics [Internet]. 2015;91:9–15.

Ranade S, Bajaj A, Londhe V, Babul N, Kao D. Fabrication of topical metered dose film forming sprays for pain management. European Journal of Pharmaceutical Sciences [Internet]. 2017;100:132–41.

Das T, Venkatesh MP, Pramod Kumar TM, Koland M. SLN based alendronate in situ gel as an implantable drug delivery system – A full factorial design approach. Journal of Drug Delivery Science and Technology. 2020;55:1–26.

Pratiwi L, Sari R, Apridamayanti P. Original Article DESIGN AND Characterization of Nanospray With Self-Nanoemulsifying Drug Delivery System Using Sinergistic Combination of Melastoma Malabathricum L . Fraction and Gentamicin. 2021;13(2).

Zurdo Schroeder I, Franke P, Schaefer UF, Lehr CM. Development and characterization of film forming polymeric solutions for skin drug delivery. European Journal of Pharmaceutics and Biopharmaceutics. 2007;65(1):111–21.

Bansal G, Garg VK, Jha KK. Formulation and evaluation of polymeric thin films of zolmitriptan. Journal of Pharmacy Research |. 2018;12(2):168.

Anter HM, Hashim IIA, Awadin W, Meshali MM. Novel anti-inflammatory film as a delivery system for the external medication with bioactive phytochemical “Apocynin.” Drug Design, Development and Therapy. 2018;12(November):2981–3001.

Anter HM, Hashim IIA, Awadin W, Meshali MM. Novel anti-inflammatory film as a delivery system for the external medication with bioactive phytochemical “Apocynin.” Drug Design, Development and Therapy. 2018;12:2981–3001.

Edwards A, Qi S, Liu F, Brown MB, McAuley WJ. Rationalising polymer selection for supersaturated film forming systems produced by an aerosol spray for the transdermal delivery of methylphenidate. European Journal of Pharmaceutics and Biopharmaceutics. 2017;114:164–74.

Zhang L, Alfano J, Race D, Davé RN. Zero-order release of poorly water-soluble drug from polymeric films made via aqueous slurry casting. European Journal of Pharmaceutical Sciences [Internet]. 2018;117(January):245–54.

Mundada A, Satturwar P, Fulzele S, Joshi S, Dorle A. Characterization and evaluation of novel film forming polymer for drug delivery. Iranian journal of pharmaceutical research : IJPR [Internet]. 2011;10(1):35–42.

Jantrawut P, Chaiwarit T, Jantanasakulwong K, Brachais CH, Chambin O. Effect of plasticizer type on tensile property and in vitro indomethacin release of thin films based on low-methoxyl pectin. Polymers. 2017;9(7).

Huang J, Deng Y, Ren J, Chen G, Wang G, Wang F, et al. Novel in situ forming hydrogel based on xanthan and chitosan re-gelifying in liquids for local drug delivery. Carbohydrate Polymers [Internet]. 2018;186(January):54–63.

Padula C, Nicoli S, Pescina S, Santi P. Thin polymeric films for the topical delivery of propranolol. Colloids and Surfaces B: Biointerfaces [Internet]. 2019;174:582–6.

Vij NN, Saudagar RB. Formulation, development and evaluation of film-forming gel for prolonged dermal delivery of terbinafine hydrochloride. International Journal of Pharma Sciences and Research (IJPSR). 2014;5(9):537–54.

Ammar HO, Ghorab M, Mahmoud AA, Makram TS, Ghoneim AM. Rapid pain relief using transdermal film forming polymeric solution of ketorolac. Pharmaceutical Development and Technology. 2013;18(5):1005–16.

Barot BS, Parejiya PB, Patel HK, Gohel MC, Shelat PK. Microemulsion-based gel of terbinafine for the treatment of onychomycosis: Optimization of formulation using D-optimal design. AAPS PharmSciTech. 2012;13(1):184–92.

Elnaggar YSR, Talaat SM, Bahey-El-Din M, Abdallah OY. Novel lecithin-integrated liquid crystalline nanogels for enhanced cutaneous targeting of terconazole: Development, in vitro and in vivo studies. International Journal of Nanomedicine. 2016;11:5531–47.

Campus B, Vishwavidyalaya GK. Original Article Effect of Polymeric Blend on Ex-Vivo Permeation Studies of Aceclofenac Loaded Film Forming Gel. 2021;13(4):1–6.

Patel DP, Setty CM, Mistry GN, Patel SL, Patel TJ, Mistry PC, et al. Development and evaluation of ethyl cellulose-based transdermal films of furosemide for improved in vitro skin permeation. AAPS PharmSciTech. 2009;10(2):437–42.

Plga-lpt-ck P, Kumar JR. Development and Antifugal Activity of Itraconazole Loaded Ethosomal Gel in Rat Animal Model. journal of pharmaceutical sciences and research. 2019;(August):5–11.

Paradkar M, Thakkar V, Soni T, Gandhi T, Gohel M. Formulation and evaluation of clotrimazole transdermal spray. Drug Development and Industrial Pharmacy [Internet]. 2015;41(10):1718–25.

Kelidari HR, Babaei R, Nabili M, Shokohi T, Saeedi M, Gholami S, et al. Improved delivery of voriconazole to Aspergillus fumigatus through solid lipid nanoparticles as an effective carrier. Colloids and Surfaces A: Physicochemical and Engineering Aspects [Internet]. 2018;558(August):338–42.

Hussain A, Samad A, Singh SK, Ahsan MN, Haque MW, Faruk A, et al. Nanoemulsion gel-based topical delivery of an antifungal drug: In vitro activity and in vivo evaluation. Drug Delivery. 2016;23(2):652–67.

Elmataeeshy ME, Sokar MS, Bahey-El-Din M, Shaker DS. Enhanced transdermal permeability of Terbinafine through novel nanoemulgel formulation; Development, in vitro and in vivo characterization. Future Journal of Pharmaceutical Sciences. 2018;4(1):18–28.

Bajaj A, Malhotra G, Madan M, Amrutiya N, Bakshi A. A novel metered dose transdermal spray formulation for oxybutynin. Indian Journal of Pharmaceutical Sciences [Internet]. 2008;70(6):733.

Geh KJ, Stelzl A, Gröne A, Wagner L, Förster B, Winter G. Development of a sprayable hydrogel formulation for the skin application of therapeutic antibodies. European Journal of Pharmaceutics and Biopharmaceutics [Internet]. 2019;142(June 2019):123–32.

Rutthapol Sritharadol, Titpawan Nakpheng, Paul Wan Sia Heng and Teerapol

Srichana “Development of a topical mupirocin spray for antibacterial and wound-healing applications,” Drug Development and Industrial Pharmacy, vol. 43, no. 10, pp. 1715–1728, 2017.

Gohel MC, Nagori SA. Fabrication of modified transport fluconazole transdermal spray containing ethyl cellulose and eudragit® RS100 as film formers. AAPS PharmSciTech. 2009;10(2):684–91.

Amanda F. Silva, Alvarez, Maíra P. Ferreira, Fabiana T. M. C. Vicentini, Vinicius Pedrazzi and Osvaldo de Freitas, “A New Approach to Ex Vivo Permeation Studies in In-Situ Film-Forming Systems,” AAPS PharmSciTech, vol. 21, no. 7, p. 257, Oct. 2020.

A. Bakshi, A. Bajaj, G. Malhotra, M. Madan and N. Amrutiyai, “A novel metered dose transdermal spray formulation for oxybutynin,” Indian Journal of Pharmaceutical Sciences, vol. 70, no. 6, p. 733, 2008.

Dhaval P. Patel et al., “Development and evaluation of ethyl cellulose-based transdermal films of furosemide for improved in vitro skin permeation,” AAPS PharmSciTech, vol. 10, no. 2, pp. 437–442, 2009.

Published

12-11-2021

How to Cite

Abdullah, N., & Patil, A. B. (2021). DESIGNING OF NOVEL TOPICAL IN SITU POLYMERIC FILM-FORMING SOLUTION SPRAY FORMULATION OF ANTIFUNGAL AGENT: IN VITRO ACTIVITY AND IN VIVO CHARACTERIZATION. International Journal of Applied Pharmaceutics, 14(1). https://doi.org/10.22159/ijap.2022v14i1.43581

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