FORMULATION AND EVALUATION OF OXICONAZOLE MUCOADHESIVE NANOEMULSION BASED GEL FOR TREATMENT OF FUNGAL VAGINAL INFECTION

Authors

  • Abeer Khattab
  • Soha Ismail

Abstract

Objective: The aim of the present study was to formulate and evaluate nanoemulsion-based gel of oxiconazole nitrate (OXZ) for the treatment of vaginal infection.

Methods: The solubility of Oxiconazole nitrate in various oils, surfactant and co-surfactant, were done to identify the components of the nanoemulsion. Based on the solubility studies, isopropyl myristate (IPM) as oil, Cremophore EL as surfactant and ethanol as co-surfactant were selected for preparing nanoemulsion. Various nanoemulsions were prepared by using the spontaneous emulsification technique. The nanoemulsion area was determined by constructing of pseudo ternary phase diagrams. The formulated nanoemulsions were subjected to accelerated stability test. The nanoemulsion formulae that passed the stability test were characterized for its morphology, droplet size, conductivity and zeta potential. These optimized formulae were incorporated into the polymeric gel of carbopol 934 (CRB), hydroxypropyl methylcellulose (HPMC), sodium carboxymethylcellulose (NaCMC) and xanthum gum (XGUM), then evaluated for pH, viscosity, bio-adhesion properties, spreadability and drug content. The in vitro release and antifungal activity of the nanoemulsion gel formulae compared with the commercial available product, tinox® cream, was carried out to judge their efficiency.

Results: The optimal nanoemulsion formulae which composed of oil, surfactant: cosurfactant mixture (1:1 or 2:1), and water in ratio 5:45:50 showed the highest stability of nanoemulsion. All the nanoemulsion gel formulae showed higher release and antifungal activity than the marketed cream.

Conclusion: The Oxiconazole nitrate nanoemulsion-based gel could be successfully promising formulation for the topical treatment of fungal vaginal candidiasis.

Keywords: Nanoemulsion, Oxiconazole nitrate, Nanoemulsion-based gel, Vaginal candidiasis, Mucoadhesion

Downloads

Download data is not yet available.

References

Lanchares JL, Hernandez ML. Recurrent vaginal candidiasis changes in etiopathogenic patterns. Int J Gynecol Obstet 2000;71: S29–S35.

Ferrer J. Vaginal candidosis: epidemiological and etiological factors. Int J Gynecol Obstet 2000;71: S21–S27.

Sobel JD. Candidal vulvovaginitis. Clin Obstet Gynecol Mar 1993;1:153–65.

Horowitz BJ, Giaquinta D, Ito S. Pathogens in vulvovaginal candidiasis: implications for patient care. J Clin Pharmacol 1992;3:248–55.

Nencioni T, Pamparana F, Jacobellis M. Mycotic vulvovaginitis and topical cyclopiroxolamine. Minerva Ginecol 1988;12:719-22.

Matsui H, Sakanashi Y, Oyama TM, Oyama Y, Yokota S, Ishida S, et al. Imidazole antifungals, but not triazole antifungals, increase membrane Zn2+permeability in rat thymocytes possible contribution to their cytotoxicity. Toxicology 2008;2-3:142-50.

Fromtling RA: Overview of medically important antifungal azole derivatives. Clin Microbiol Rev 1988 Apr; 2:187-217.

Polak A. Antifungal activity of four antifungal drugs in the cutaneous retention time test. Sabouraudia 1984;22:501-3.

Ramelet AA, Walker-Nasir E. One daily application of oxiconazole nitrate cream is sufficient for treating dermatomycoses. Dermatologica 1987;175:293-5.

Gouveia DC, Jones DA, Silva C. Oxiconazole nitrate in the treatment of vaginal candidiasis: single dose versus 3-day treatment with econazole. Pharmatherapeutica 1984;10:682-5.

Gip L. Comparison of oxiconazole nitrate (Ro 13-8996) and econazole in dermatomycoses. Mykosen 1984;27:295-302.

Wagner W, Reckers-Czaschka R. Oxiconazole nitrate in dermatomycosis: a double-blind, randomized comparison with bifonazol. Mykosen 1987;30:484-92.

Sharma G, Jain S, Tiwary K, Kayr G. once daily bioadhesive vaginal clotrimazole tablets: design and evaluation. Acta Pharm 2006;56:337-45.

Adnan A, Mohammad R, Farhan JA, Zeenat I, Roop KK, Aqil M, Sushama T. Nanoemulsion components screening and selection: a technical note. AAPS Pharm Sci Tech 2009;1:69-76.

AzeemA, Rizwan M. Nanoemulsion components screening and selection: A technical note. AAPS Pharm Sci Tech 2009;10:69-76.

Patel MR, Patel RB, Parikh JR, Solanki AB, Patel BG. Effect of formulation components on the in vitro permeation of microemulsion drug delivery system of fluconazole. AAPS PharmSci Tech 2009;10:917-23.

Kantarci G, Ozguney I, Karasulu HY, Arzik S, Guneri T. Comparison of different water/oil microemulsions containing diclofenac sodium Preparation, characterization, release rate, skin irritation studies. AAPS Pharm Sci Tech 2007;8:E91.

Mohamed MI. Optimization of chlorphenesin Emulgel Formulation. AAPS 2004;3:e26.

Yogeshwar G. Bachhav, Vandana B. Patravale. The microemulsion-based vaginal gel of clotrimazole: Formulation, in vitro evaluation, and stability studies. AAPS Pharm Sci Tech June 2009;2:476-81.

Ghada H. Formulation and In-vitro evaluation of nyatatin nanoemulsion-based gel for topical delivery. J Am Sci 2012;12:541-8.

Shafiq S, Shakeel F, Talegaonkar S, Ali J, Baboota S, Ahuja A, Khar RK, Ali M. Formulation development and optimization using nanoemulsion technique: A technical note. AAPS Pharm. Sci. Tech. 2007;2: E1-E6.

Sushama T, Mohd T and Raid MA. Design and development of o/w nanoemulsion for the transdermal delivery of ondansetron. Bulletin of pharmaceutical Research 2011;3:18-30.

Shakeel F, Baboota S, Ahuja A, Ali J, Aquil M, Shafiq S. Nanoemulsions a Vehicle for Transdermal Delivery of Aceclofenac. AAPS Pharm Sci Tech 2007;4: E1-E9.

Yashpal S, Tanuj H, Harsh K. Nanoemulsions: A pharmaceutical review. Nanoemulsions — Advances in Formulation, Characterization, and Applications in Drug Delivery. Int J Pharma Prof Res 2013;2:928-35.

Faiyaz S, Wafa R, Musa A. Investigation of true nanoemulsions for the transdermal potential of indomethacin: Characterization, rheological characteristics and ex vivo skin permeation studies. J Drug Target 2009;17:435-41.

Singh B, Kumar B, Jain SK, Shafaat K. Development and characterization of A nanoemulsion gel formulation for transdermal delivery of carvedilol. Int. J. Drug Dev Res Jan-March 2012;1:151-61.

Sripriya V, Jun S. Self-nano emulsifying drug delivery systems (SNEDDS) for oral delivery of protein drugs I. Formulation development Int J Pharm October 2008;1-2:2-9.

Pradhnya W, Swapnil W, Ashwini Y. Development of isotretinoin gel for the treatment of acne vulgaris. Research Journal of Pharmaceutical, Biological and Chemical Sciences January–March 2011;1:220-30.

Desai KG. Enhanced Skin Permeation of rofecoxib using topical microemulsion gel. Drug Dev Res 2004;63:33–40.

Bachhav YG, Patravale VB. The microemulsion based vaginal gel of fluconazole: Formulation, in vitro and in vivo evaluation. Int J Pharm 2009;365:175–9

Nakamura F, Ohta R, Machida Y, Nagai T. In vitro and in vivo nasal mucoadhesion of some water-soluble polymers. Int J Pharm 1996;134:173–81.

Shiva KY, Naveen KN, Sharada Goranti, Sambit KD. Development of intravaginal metronidazole gel for the treatment of bacterial vaginosis: Effect of Mucoadhesive natural polymers on the release of Metronidazole. Int J PharmTech Res 2010;3:1746-50.

Chudasama A, Patel V, Nivsarcar M, Vasu K, Shishoo C. Investigation of microemulsion system for transdermal delivery of itraconazole. J Adv Pharm Technol Res 2011;2:30-8.

Faiyaz S, Sanjula B, Alka A, Javed A, Mohammed A, Sheikh S. Nanoemulsions as vehicles for transdermal delivery of aceclofenac. AAPS Pharm Sci Tech 2007;8:4.

Kommuru TR, Gurley B, Khan MA, Reddy IK. Self emulsifying drug delivery systems) (SEDDS) of coenzyme Q10: Formulation development and bioavailability assessment. Int J Pharm 2001;2:233-46.

Lawrence MJ. Surfactant systems (SEDDS): microemulsions and vehicles as vehicles for drug delivery. Eur J Drug Metab Pharmacokinet 1994;3:2257-69.

Lawrence MJ, Rees GD. Microemulsion-based media as novel drug delivery systems. Adv Drug Deliv Rev 2000;1:89-121.

Chhabra G, Chuttani K, Mishra AK, Pathak K. Design and development of nanoemulsion drug delivery system of amlodipine besilate for improvement of oral bioavailability. Drug Dev Ind Pharam 2011;8:907-16.

Aboofazeli R, Lawrence CB, Wicks SR, Lawrence MJ. The investigation into formation and characterization of phospholipid microemulsions III. Pseudo-trnary phase diagrams and either an alkanoic acid, amine alkane diol, polyethylene glyol alkyl ether or alcohol as cosurfactant. Int J Pharm 1994;1:63-72.

Ghosh PK, Murthy RSR. Microemulsions: a potential drug delivery system. Curr Drug Delivery 2006;2:167-80.

Kreilgaard M. Influence of microemulsions on cutanteous drug delivery. Adv Drug Delivery 2002;54: S77-98.

Hua L, Weisan P, Jiayu L, Ying Z. Preparation, evaluation, and NMR characterization of vinpocetine microemulsion for transdermal delivery. Drug Dev Ind Pharm 2004;6:657-66.

Gao ZG, Choi HG, Shin HJ, Park KM, Lim SJ, Hwang KJ, et al. Physicochemical characterization and evaluation of microemulsion system for oral delivery of cyclosporine A. Int J Pharm 1998;161:75-86.

Mruali RP, Rashim BP, Jolly RP. Effect of formulation components on the in vitro permeation of microemulsion drug delivery system of fluconazole. AAPS Pharm Sci Tech 2009;10:917-23.

Gulam M, Khan, Zeenat I, Bansal T, Talegaonkar S. Preparation and characterization of oil in water nano-reservoir systems for improved oral delivery of atorvastatin. Curr Nanosci 2009;13:428-40.

Hasse A, Keipert S. Development and characterization of microemulsions for ocular application. Eur J Pharm Biopharm 1997;43:179-83.

Farhan JA, Mohd AA, Zeenate IK, Roop KK, Mushir A. Development and in vitro evaluation of an acid-buffering bioadhesive vaginal gel for mixed vaginal infection. Acta Pharm 2008;58:407-19.

Mortazavi SA, Smart JD. Factors influencing gel-strengthening at the mucoadhesive-mucus interface. J Pharm Pharmacol 1994;46:86-90.

Mortazavi SA. Investigation of various parameters influencing the duration of mucoadhesion of some polymers containing discs. Daur 2002;10:98-104.

Anita P, Jayvadan P. Mucoadhesive microemulsion based prolonged release vaginal gel for the anti-fungal drug. Am J PharmTech Res 2012;2:4.

Published

01-03-2016

How to Cite

Khattab, A., and S. Ismail. “FORMULATION AND EVALUATION OF OXICONAZOLE MUCOADHESIVE NANOEMULSION BASED GEL FOR TREATMENT OF FUNGAL VAGINAL INFECTION”. International Journal of Pharmacy and Pharmaceutical Sciences, vol. 8, no. 3, Mar. 2016, pp. 33-40, https://www.innovareacademics.in/journals/index.php/ijpps/article/view/9885.

Issue

Section

Original Article(s)