Development and optimization of nanoemulsion gel for topical delivery of imiquimod

doi:10.5246/jcps.2018.01.004

Abstract

Abstract:

In the present study, we aimed to formulate, optimize and characterize nanoemulsion-based gel of imiquimod for its topical administration and to improve the drug permeation. Nanoemulsions were prepared by the aqueous phase titration method and spontaneously formed by mixing specific fractions of oil phase:S_mix:water. The nanoemulsion formulations were optimized by response surface methodology (RSM) using mixture design, Scheffe model. The formulated nanoemulsion was incorporated into 0.5% Carbopol 934 (w/v) to enhance convenience in superficial application of the drug. The nanoemulsions were characterizedin terms of droplet size, zeta potential, TEM, DSC and in vitro drug permeation. The vesicle size was 113.6 nm with polydispersity index of 0.251. The zeta potential was 34 mV. The spherical droplet shape was confirmed by TEM analysis. The drug permeation from the diffusion membrane was 73.67% in 6 h for the optimized formulation. An optimized nanoemulsion gel formulation of imiquimod was successfully developed with improved permeation using experimental design technique. The developed formulation could be further explored as a potential alternate to currently available topical formulations for the treatment of genital warts.

Key words: Imiquimod, Condyloma acuminata, Human papilloma virus, Genital warts, Nanoemulsions

CLC Number:

R944

Supporting:

Gurvinder Kaur, Tanurajvir Kaur, Deepak N. Kapoor. Development and optimization of nanoemulsion gel for topical delivery of imiquimod[J]. Journal of Chinese Pharmaceutical Sciences, 2018, 27(1): 31-39.

References

[1] Shafiq-un-Nabi, S.; Shakeel, F.; Talegaonkar, S.; Ali, J.; Baboota, S.; Ahuja, A.; Khar, R.K.; Ali, M. Formulation Development and Optimization using Nanoemulsion Technique: A Technical Note. AAPS. PharmSciTech. 2007, 8, 1-6.

[2] Azeem, A.; Rizwan, M.; Ahmad, F.Z.; Iqbal, Z.; Khar, R.K.; Aqil, M.; Talegaonkar, S. Nanoemulsion Components Screening and Selection: A Technical Note. AAPS. PharmSciTech. 2009, 10, 69-76.

[3] Debnath, S.; Satayanarayana Kumar, G.V. Nanoemulsion: A Method to Improve the Solubility of Lipophilic Drugs. Int. J. Pharm. Sci. 2011, 2, 72-84.

[4] Devarajan, V.; Ravichandran, V. Nanoemulsions: As Modified Drug Delivery Tool. Int. J. Comp. Pharm. 2011, 2, 1-6.

[5] Maali, A.; Mosavian, M.T.H. Preparation and Application of Nanoemulsions in the Last Decade (2000-2010). J. Disper. Sci. Technol. 2013, 34, 92-105.

[6] Rapose, A. Human PapillomaVirus and Genital Cancer. Ind. J. Derm.Venereol Leprol. 2009, 75, 236-244.

[7] Tchernev, G. Sexually Transmitted Papillomavirus Infections: Epidemiology, Pathogenesis, Clinic, Morphology, Important Differential Diagnostic Aspects, Current Diagnostic and Treatment Options. An. Bras. Derma. 2009, 84, 377-389.

[8] Sharma, S. Vaccines Against Human Papilloma Virus and Cervical Cancer: An Overview. Ind. J. Community Med. 2008, 33, 143-146.

[9] Gall, S.A. Female Genital Warts: Global Trends and Treatments. Inf. Dis. Obs. Gyne. 2001, 9, 149-154.

[10] Kodner, C.M.; Nastraty, S. Management of Genital Warts. Am. Fam. Physician. 2004, 70, 2335-2342.

[11] Tarbet, E.B.; Larson, D.; Anderson, B.J.; Bailey, K.W.; Wong, M.; Smee, D.F. Evaluation of Imiquimod for Topical Treatment of Vaccinia Virus Cutaneous Infections in Immunosuppressed Hairless Mice. Antiviral Res. 2011, 90, 126-133.

[12] Vidal, D.; Alomar, A. Mode of Action and Clinical Use of Imiquimod. Expert Rev Dermatol. 2008, 3, 151-159.

[13] Homhuan, A. Maturation of Dendritic Cells Induced by Nano-liposomes Containing Imiquimod. Asian Biomed. 2008, 2, 233-239.

[14] Lacarrubba, F.; Nasc, M.R.; Micali, G. Advances in the Use of Topical Imiquimod to Treat Dermatologic Disorders. Ther. Clin. Risk Manag. 2008, 4, 87-97.

[15] Lee, W.; Shen, S.; Al-Suwayeh, S.A.; Yang, H.; Yuan, C.; Fang, J. Laser-Assisted Topical Drug Delivery by Using a Low-fluence Fractional Laser: Imiquimod and Macro-molecules. J. Controlled Release. 2011, 153, 240-248.

[16] Tyring, S.K.; Arany, I.; Stanley, M.A.; Tomai, M.A.; Miller, R.L.; Smith, M.H.; Dermott, D.J.; Slade, H.B. A Randomized, Controlled, Molecular Study of Condyloma acuminata Clearance During Treatment with Imiquimod. J. Infect. Dis. 1998, 178, 551-555.

[17] Kapil, R.; Dhawan, S.; Singh, B. Development and Validation of a Spectrofluorimetric Method for the Estimation of Rivastigmine in Formulations. Ind. J. Pharm. Sci. 2009, 71, 581-585.

[18] Kumar, S.H.; Singh, V. J. Nanoemulsification: A Novel Targeted Drug Delivery Tool. Drug Deliv. Ther. 2012, 2, 40-45.

[19] Patel, R.P.; Joshi, J.R. An Overview on Nanoemulsion: A Novel Approach. Int. J. Pharm. Sci. Res. 2012, 3, 4640-4650.

[20] Shakeel, F.; Baboota, S.; Ahuja, A.; Javed, A.; Shafiq, S. Accelerated Stability Testing of Celecoxib Nanoemulsion containing Cremophor-EL. Afri. J. Pharm. Pharmacol. 2008, 2, 179-183.

[21] Gupta, P.K.; Pandit, J.K.; Kumar, A.; Swaroop, P.; Gupta, S. Pharmaceutical Nanotechnology Novel Nanoemulsion-High Energy Emulsification Preparation, Evaluation and Application. Pharm. Res. 2010, 3, 117-138.

[22] Zheng, W.; Zhao, L.; Wei, Y.M.; Ye, Y.; Xiao, S.H. Preparation and In vitro Evaluation of Nanoemulsion System for the Transdermal Delivery of Granisetron Hydrochloride. Chem. Pharm. Bull. 2010, 58, 1015-1019.
[23] Modi, J.D.; Patel, J.K. Nanoemulsion-Based Gel Formulation of Aceclofenac for Topical Delivery. Int. J. Pharm. Sci. Res. 2011, 1, 6-12.