TOPICAL NANOEMULSION-BASED GEL OF ISOCONAZOLE NITRATE

Authors

  • Mowafaq M. Ghareeb Department of Pharmaceutics, College of Pharmacy, Baghdad University, Baghdad, Iraq
  • Mariam S. Mohammed Department of Pharmaceutics, College of Pharmacy, Mustansiriyah University, Baghdad, Iraq

DOI:

https://doi.org/10.32947/ajps.v23i4.1093

Keywords:

Nanoemulsion, Pseudoternary phase diagram, Isoconazole nitrate, Topical

Abstract

This study aimed to make an o/w
nanoemulsion of isoconazole the drug
nitrate (ISN) for topical use. Low
aqueous solubility is a characteristic
feature of the imidazole antifungal ISN.
Therefore, ISN nanoemulsion would increase dispersibility and decreases skin resistance by
enhancing the drug penetration to the first layers of skin (stratum corneum). The work
included constructing the pseudo-ternary phase diagrams by using the aqueous titration
method. The prepared o/w nanoemulsions were composed of oil, Smix (a mixture of
surfactant and co-surfactant) and deionized water (DW). ISN nanoemulsions were subjected
to characterization studies to choose the best formula. According to the characterization
studies, the optimal formula, designated NE14 contains 1% ISN, 66% Smix ((1:3) tween60:
propylene glycol:ethanol), 7% oleic acid, and 27% deionized water was reached. Formula
NE14 is characterized by having a polydispersity index of (0.146), pH (5.76), droplet size
(84.6 nm), percent transmittance (98.8%), viscosity (80m Pa.s) and a high release of
isoconazole propably due low viscosity. The droplet size of NE14 (84.6nm) was also
confirmed by an atomic force microscopy (AFM) research. The improved formula (ISN
NE14) was found to be a promising nanoemulsion formula for enhancing the topical
bioavailability of ISN and thus could increase its efficacy for the treatment of topical fungal
infections.

References

- B. V Mitkari, S. A. Korde, K. R. Mahadik, and C. R. Kokare, “Formulation and Evaluation of Topical Liposomal Gel for Fluconazole,” ndian J.Pharm. Educ. Res., vol. 44, no. 4, pp. 324–333, 2010.

- A. Hussain, V. K. Singh, O. P. Singh, K. Shafaat, S. Kumar, and F. J. Ahmad, “Formulation and optimization of nanoemulsion using antifungal lipid and surfactant for accentuated topical delivery of Amphotericin B,” Drug Deliv., vol. 23, no. 8, pp. 3101–3110, 2016, doi: 10.3109/10717544.2016.1153747. DOI: https://doi.org/10.3109/10717544.2016.1153747

- G. Coneac et al., “Development and Evaluation of New Microemulsion-Based Hydrogel Formulations for Topical Delivery of Fluconazole,” AAPS PharmSciTech, vol. 16, no. 4, pp. 889–904, 2015, doi: 10.1208/s12249-014-0275-8. DOI: https://doi.org/10.1208/s12249-014-0275-8

- Zainab H. Mahdi. Ibtihal Abdul kadhim Dakhil, “An Overview on the Recent Technologies and Advances in Drug Delivery of Poorly Water-Soluble Drugs,” Al Mustansiriyah J. Pharm. Sci., vol. 19, no. 4, 2019. DOI: https://doi.org/10.32947/ajps.v19i4.649

- M. Jaiswal, R. Dudhe, and P. K. Sharma, “Nanoemulsion: an advanced mode of drug delivery system,” 3 Biotech Springerlink, vol. 5, no. 2, pp. 123–127, 2015, doi: 10.1007/s13205-014-0214-0. DOI: https://doi.org/10.1007/s13205-014-0214-0

- A. Brayfield, BPharm, and MRPharmS, Martindale The Complete Drug Reference,Thirty-eighth Edition ,volume 3,Pharmaceutical Press. 2014.

- S. Veraldi, “Isoconazole nitrate: a unique broad-spectrum antimicrobial azole effective in the treatment of dermatomycoses, both as monotherapy and in combination with corticosteroids,” Blackwell Verlag GmbH, vol. 56, no. 1, pp. 3–15, 2013, doi: 10.1111/myc.12054. DOI: https://doi.org/10.1111/myc.12054

- M. S. P. Desai, R.R. Patlolla, “Interaction of nanoparticles and cell-penetrating peptides with skin for transdermal drug delivery,” Molec. Membr. Biol., vol. 27, 2010. DOI: https://doi.org/10.3109/09687688.2010.522203

- J. Kaewbanjong, T. Amnuaikit, and P. Boonme, “Formulation and Characterization of Clotrimazole Microemulsions and Microemulsion-Based Gels,” Int. J. Nanosci., vol. 13, no. 4, pp. 1–6, 2014, doi: 10.1142/S0219581X14400055. DOI: https://doi.org/10.1142/S0219581X14400055

- M. Saleem and M. Ghareeb, “Nanoemulsion as a new advanced technology of drug delivery system,” NeuroQuantology, vol. 20, no. 11, pp. 2831–2836, 2022, doi: 10.14704/NQ.2022.20.11.NQ66291.

- S. R. Botros, A. K. Hussein, and H. F. Mansour, “A Novel Nanoemulsion Intermediate Gel as a Promising Approach for Delivery of Itraconazole: Design, In Vitro and Ex Vivo Appraisal,” AAPS PharmSciTech, vol. 21, no. 7, pp. 12–14, 2020, doi: 10.1208/s12249-020-01830-w. DOI: https://doi.org/10.1208/s12249-020-01830-w

- J. Dykes, R. Marks, and U. Tauber, “The retention of isoconazole in the skin after once or twice daily application of 1 " o isoconazole nitrate cream ( Travogen ® ) over a 14-day period,” Clin. Exp. Dermatotogy, vol. 11, pp. 365–370, 1986. DOI: https://doi.org/10.1111/j.1365-2230.1986.tb00476.x

- A. Antunes, S. Araújo, S. Bezerra, and S. Storpirtis, “Determination of the melting temperature , heat of fusion , and purity analysis of different samples of zidovudine ( AZT ) using DSC,” Brazilian J. Pharm. Sci., vol. 46, no. 1, p. :37–43, 2010. DOI: https://doi.org/10.1590/S1984-82502010000100005

- A. N. Wannas and N. K. Maraie, “Preparation and in-vitro evaluation of cilostazol self-emulsifying drug delivery system,” Al Mustansiriyah J. Pharm. Sci., vol. 20, no. 1, 2020. DOI: https://doi.org/10.32947/ajps.v20i1.682

- R. Pathak, R. Prasad, and M. Misra, “Role of mucoadhesive polymers in enhancing delivery of nimodipine microemulsion to brain via intranasal route,” Acta Pharm. Sin. B, vol. 4, no. 2, pp. 151–160, 2014, doi: 10.1016/j.apsb.2014.02.002. DOI: https://doi.org/10.1016/j.apsb.2014.02.002

- S. Asadinezhad, F. Khodaiyan, M. Salami, H. Hosseini, and B. Ghanbarzadeh, “Effect of different parameters on orange oil nanoemulsion particle size: combination of low energy and high energy methods,” J. Food Meas. Charact., vol. 13, no. 4, pp. 2501–2509, 2019, doi: 10.1007/s11694-019-00170-z. DOI: https://doi.org/10.1007/s11694-019-00170-z

- M. Ghareeb and A. J. Neamah, “FORMULATION AND CHARACTERIZATION OF NIMODIPINE NANOEMULSION AS,” Int. J. Pharm. Sci. Res., vol. 8, no. 2, pp. 591–602, 2017, doi: 10.13040/IJPSR.0975-8232.8(2).591-02. DOI: https://doi.org/10.13040/IJPSR.0975-8232.8(2).591-02

- S. K. Sah, A. Badola, and S. Mukhopadhyay, “Development and evaluation of tioconazole loaded emulgel,” Int. J. Appl. Pharm., vol. 9, no. 5, pp. 83–90, 2017, doi: 10.22159/ijap.2017v9i5.20046. DOI: https://doi.org/10.22159/ijap.2017v9i5.20046

- M. N. Formulation, E. Asian, P. Koteswari, S. R. Krishna, V. Prabhakar, and R. Lakshmi, “FORMULATION AND PREPARATION OF FELODIPINE NANOEMULSIONS,” Asian J. Pharm. Clin. Res., vol. 4, no. 1, pp. 116–117, 2011.

- Y. Sohn et al., “Development of self-microemulsifying bilayer tablets for pH-independent fast release of candesartan cilexetil,” Pharmazie, vol. 67, no. 11, pp. 917–924, 2012, doi: 10.1691/ph.2012.2003.

- S. M. Alshahrani, “Anti-inflammatory Studies of Ostrich Oil Based Nanoemulsion,” J. Oleo Sci., vol. 208, no. 3, pp. 203–208, 2019. DOI: https://doi.org/10.5650/jos.ess18213

- L. Pratiwi, A. Fudholi, R. Martien, and S. Pramono, “Design and optimization of self-nanoemulsifying drug delivery systems (SNEDDS) of ethyl acetate fraction from mangosteen peel (garcinia mangostana, L.),” Int. J. PharmTech Res., vol. 9, no. 6, pp. 380–387, 2016. DOI: https://doi.org/10.5530/jyp.2017.9.68

- H. K. Alkufi and H. J. Kassab, “Formulation and evaluation of sustained release sumatriptan mucoadhesive intranasal in-situ gel,” Iraqi J. Pharm. Sci., vol. 28, no. 2, pp. 95–104, 2019, doi: 10.31351/vol28iss2pp95-104. DOI: https://doi.org/10.31351/vol28iss2pp95-104

- Mowafaq M. Ghareeb, “Formulation and characterization of rizatriptan benzoate as intranasal nanoemulgel,” Int. J. Drug Deliv. Technol., vol. 12, no. 2, pp. 546-552., 2022.

- M. Asikoglu, G. Ertan, and G. Cosar, “The Release of Isoconazole Nitrate from Different Suppository Bases: In‐vitro Dissolution, Physicochemical and Microbiological Studies,” J. Pharm. Pharmacol., vol. 47, no. 9, pp. 713–716, 1995, doi: 10.1111/j.2042-7158.1995.tb06728.x. DOI: https://doi.org/10.1111/j.2042-7158.1995.tb06728.x

- M. Bayanati, A. G. Khosroshahi, M. Alvandi, and M. M. Mahboobian, “Fabrication of a Thermosensitive in Situ Gel Nanoemulsion for Nose to Brain Delivery of Temozolomide,” J. Nanomater., vol. 2021, 2021, doi: 10.1155/2021/1546798. DOI: https://doi.org/10.1155/2021/1546798

- O. Samia, R. Hanan, and E. T. Kamal, “Carbamazepine Mucoadhesive Nanoemulgel (MNEG) as brain targeting delivery system via the olfactory mucosa,” Drug Deliv., vol. 19, no. 1, pp. 58–67, 2012, doi: 10.3109/10717544.2011.644349. DOI: https://doi.org/10.3109/10717544.2011.644349

- D. M. Mostafa et al., “Transdermal fennel essential oil nanoemulsions with promising hepatic dysfunction healing effect: in vitro and in vivo study,” Pharm. Dev. Technol., vol. 24, no. 6, pp. 729–738, 2019, doi: 10.1080/10837450.2019.1584633. DOI: https://doi.org/10.1080/10837450.2019.1584633

- R. Kaur and M. Ajitha, “Transdermal delivery of fluvastatin loaded nanoemulsion gel: Preparation, characterization and in vivo anti-osteoporosis activity,” Eur. J. Pharm. Sci., vol. 136, pp. 1–10, 2019, doi: 10.1016/j.ejps.2019.104956. DOI: https://doi.org/10.1016/j.ejps.2019.104956

- N. Laothaweerungsawat, W. Neimkhum, S. Anuchapreeda, J. Sirithunyalug, and W. Chaiyana, “Transdermal delivery enhancement of carvacrol from Origanum vulgare L. essential oil by microemulsion,” Int. J. Pharm., vol. 579, pp. 1–15, 2020, doi: 10.1016/j.ijpharm.2020.119052. DOI: https://doi.org/10.1016/j.ijpharm.2020.119052

- J. D. da Silva, M. V. Gomes, L. M. Cabral, and V. P. de Sousa, “Evaluation of the in vitro release and permeation of Cordia verbenacea DC essential oil from topical dosage forms,” J. Drug Deliv. Sci. Technol., vol. 53, pp. 1–32, 2019, doi: 10.1016/j.jddst.2019.101173. DOI: https://doi.org/10.1016/j.jddst.2019.101173

- P. Wavikar and P. Vavia, “Nanolipidgel for Enhanced Skin Deposition and Improved Antifungal Activity,” AAPS PharmSciTech, vol. 14, no. 1, pp. 222–233, 2013, doi: 10.1208/s12249-012-9908-y. DOI: https://doi.org/10.1208/s12249-012-9908-y

- K. G. A. S. K. SINGH*, “Review of Nanoemulsion Formulation and Characterization Techniques,” Indian J Pharm Sci, vol. 80, no. 5, pp. 781–789, 2018. DOI: https://doi.org/10.4172/pharmaceutical-sciences.1000422

- M. Oćwieja, M. Morga, and Z. Adamczyk, “Self-assembled silver nanoparticles monolayers on mica-AFM, SEM, and electrokinetic characteristics,” J Nanopart Res, vol. 15, no. 3, p. :1460, 2013, doi: 10.1007/s11051-013-1460-5. DOI: https://doi.org/10.1007/s11051-013-1460-5

- S. T. Nasser, A. A. Abdulrassol, and M. M. Ghareeb, “Design, preparation, and in-vitro evaluation of novel ocular antifungal nanoemulsion using posaconazole as a model drug,” Int. J. Drug Deliv. Technol., vol. 11, no. 3, pp. 1058–1064, 2021, doi: 10.25258/ijddt.11.3.71.

- V. Kumar, S. Mahant, R. Rao, and S. Nanda, “Emulgel based topical delivery system for loratadine,” ADMET DMPK, vol. 2, no. 4, pp. 254–271, 2014, doi: 10.5599/admet.2.4.64. DOI: https://doi.org/10.5599/admet.2.4.64

- S. Liu et al., “Transdermal delivery of relatively high molecular weight drugs using novel self-dissolving microneedle arrays fabricated from hyaluronic acid and their characteristics and safety after application to the skin,” Eur. J. Pharm. Biopharm., vol. 86, no. 2, pp. 267–276, 2014, doi: 10.1016/j.ejpb.2013.10.001. DOI: https://doi.org/10.1016/j.ejpb.2013.10.001

- M. Kazi, M. Al-swairi, A. Ahmad, and M. Raish, “Evaluation of Self-Nanoemulsifying Drug Delivery Systems ( SNEDDS ) for Poorly Water-Soluble Talinolol : Preparation , in vitro and in vivo Assessment,” Front. Pharmacol., vol. 10, no. May, pp. 1–13, 2019, doi: 10.3389/fphar.2019.00459. DOI: https://doi.org/10.3389/fphar.2019.00459

- M. Hanifah and M. Jufri, “Formulation and stability testing of nanoemulsion lotion containing centella asiatica extract,” J. Young Pharm., vol. 10, no. 4, pp. 404–408, 2018, doi: 10.5530/jyp.2018.10.89. DOI: https://doi.org/10.5530/jyp.2018.10.89

- S. Alam et al., “Microemulsion as a potential transdermal carrier for poorly water soluble antifungal drug itraconazole,” J. Dispers. Sci. Technol., vol. 31, no. 1, pp. 84–94, 2010, doi: 10.1080/01932690903107265. DOI: https://doi.org/10.1080/01932690903107265

- M. H. F. Sakeena, S. M. Elrashid, A. S. Munavvar, and M. N. Azmin, “Effects of Oil and Drug Concentrations on Droplets Size of Palm Oil Esters (POEs) Nanoemulsion,” J. Oleo Sci., vol. 60, no. 4, pp. 155–158, 2011, doi: 10.5650/jos.60.155. DOI: https://doi.org/10.5650/jos.60.155

- N. A. Jassem and N. A. Rajab, “Formulation and in Vitro Evaluation of Azilsartan Medoxomil Nanosuspension,” Int. J. Pharm. Pharm. Sci., vol. 9, no. 7, p. 110, 2017, doi: 10.22159/ijpps.2017v9i7.18917. DOI: https://doi.org/10.22159/ijpps.2017v9i7.18917

- S. A. A. Radwan, A. N. ElMeshad, and R. A. Shoukri, “Microemulsion loaded hydrogel as a promising vehicle for dermal delivery of the antifungal sertaconazole: design, optimization and ex vivo evaluation,” Drug Dev. Ind. Pharm., vol. 43, no. 8, pp. 1351–1365, 2017, doi: 10.1080/03639045.2017.1318899. DOI: https://doi.org/10.1080/03639045.2017.1318899

- Sita V G and P. Vavia, “Bromocriptine Nanoemulsion-Loaded Transdermal Gel: Optimization Using Factorial Design, In Vitro and In Vivo Evaluation,” AAPS PharmSciTech, vol. 21, no. 3, 2020, doi: 10.1208/s12249-020-1620-8. DOI: https://doi.org/10.1208/s12249-020-1620-8

- R. A. Dahash and N. A. Rajab, “Formulation and investigation of lacidipine as a nanoemulsions,” Iraqi J. Pharm. Sci., vol. 29, no. 1, pp. 41–54, 2020, doi: 10.31351/VOL29ISS1PP41-54. DOI: https://doi.org/10.31351/vol29iss1pp41-54

- N. A. Sadoon and M. M. Ghareeb, “Formulation and Characterization of Isradipine as Oral Nanoemulsion,” Iraqi J Pharm Sci, vol. 29, no. 1, pp. 143–153, 2020. DOI: https://doi.org/10.31351/vol29iss1pp143-153

- A. Ivancic, F. Macaev, F. Aksakal, V. Boldescu, S. Pogrebnoi, and G. Duca, “Preparation of alginate-chitosan-cyclodextrin micro- and nanoparticles loaded with anti-tuberculosis compounds,” Beilstein J. Nanotechnol., vol. 7, no. 1, pp. 1208–1218, 2016, doi: 10.3762/bjnano.7.112. DOI: https://doi.org/10.3762/bjnano.7.112

- C. Preetz, A. Hauser, G. Hause, A. Kramer, and K. Mäder, “Application of atomic force microscopy and ultrasonic resonator technology on nanoscale: Distinction of nanoemulsions from nanocapsules,” Eur. J. Pharm. Sci., vol. 39, no. 1–3, pp. 141–151, 2010, doi: 10.1016/j.ejps.2009.11.009. DOI: https://doi.org/10.1016/j.ejps.2009.11.009

- V. Ghosh, A. Mukherjee, and N. Chandrasekaran, “Ultrasonic emulsification of food-grade nanoemulsion formulation and evaluation of its bactericidal activity,” Ultrason. Sonochem., vol. 20, no. 1, pp. 338–344, 2013, doi: 10.1016/j.ultsonch.2012.08.010. DOI: https://doi.org/10.1016/j.ultsonch.2012.08.010

- A. Zarnke et al., “Physical and chemical characterization of McIntyre Powder: An aluminum dust inhaled by miners to combat silicosis,” J. Occup. Environ. Hyg., vol. 16, no. 11, pp. 745–756, 2019, doi: 10.1080/15459624.2019.1657581. DOI: https://doi.org/10.1080/15459624.2019.1657581

- D. I. Nesseem, “Formulation and evaluation of itraconazole via liquid crystal for topical delivery system,” J. Pharm. Biomed. Anal., vol. 26, no. 3, pp. 387–399, 2001, doi: 10.1016/S0731-7085(01)00414-9. DOI: https://doi.org/10.1016/S0731-7085(01)00414-9

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2023-10-09

How to Cite

Mowafaq M. Ghareeb, & Mariam S. Mohammed. (2023). TOPICAL NANOEMULSION-BASED GEL OF ISOCONAZOLE NITRATE . Al Mustansiriyah Journal of Pharmaceutical Sciences, 23(4), 378–396. https://doi.org/10.32947/ajps.v23i4.1093

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Vol. 23 No. 4 (2023): (Volume23,Issue4,Year2023)

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