DEVELOPMENT AND CLINICAL EVALUATION OF TOPICAL HYDROQUINONE NIOSOMAL GEL FORMULATION FOR THE TREATMENT OF MELASMA

  • AMAL A. AMMAR Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Al-Azhar University, Egypt
  • HODA A. SALEM Department of Clinical Pharmacy, Faculty of Pharmacy, Al-Azhar University, Egypt and Tabuk University, Saudi Arabia
  • SHEREEN A. ELADAWY Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Al-Azhar University, Egypt
  • ZINAB I. ABD ELSAMAD Department of Dermatology and Venereology, Faculty of Medicine, Tanta University, Egypt
  • NEVEEN A. KOHAF Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Al-Azhar University, Egypt

Abstract

Objective: The goal of the present study was to develop niosomal gel as a nanocarrier for improved depigmentation effect of hydroquinone (HQ). As well as to evaluate the prepared niosomes for entrapment efficiency, transmission electron microscopy (TEM), zeta potential, and in vitro release study. As an ultimate point of the objectives was to evaluate the best-prepared niosomal gel formula clinically in well-diagnosed patients of melasma and the results were compared with a commercial product.


Methods: The effect of incorporation of co-surfactant such as Tween 20, Tween 40, and Tween 60 with Span 80, was studied to determine the highest entrapment efficiency and the desired release rate. Niosomes showed the highest entrapment efficiency was incorporated in different gelling agents like Carbopol 934 and Carboxymethylcellulose sodium (CMC Na) with different concentrations. Accelerated stability testing of HQ from niosomal gel formulations; the expiry date t90 was estimated. The best-prepared niosomal gel formula was studied clinically in patients of melasma and the results were compared with the commercial product (Clearique 2%)®Delta Pharma Company. 


Results: There was a significant increase in the clinical efficacy of the niosomal therapy and a highly significant decrease regarding to modified melasma area and severity index (MASI), duration to achieve improvement, side effects, and the recurrence of melasma in patients treated with niosomal gel compared to the commercial product.


Conclusion: The incorporation of hydroquinone in niosomal gel improves its therapeutic effect regarding clinical effect, duration of treatment, side effects, recurrence and patient compliance.

Keywords: Hydroquinone, Niosomes, Niosomal gel, Surfactants, Co-surfactants, In vitro drug release study, Depigmentation effect

References

1. Jagannathan M, Sadagopan K, Ekkarakudy J, Anandan H. Clinico-epidemiological study of patients with melasma in a tertiary care hospital. A prospective study. Int J Sci Study 2017;4:117-20.
2. Achar A, Raithi SK. Melasma: a clinico-epidemiological study of 312 cases. Indian J Dermatol 2011;56:380-2.
3. Lyndle CB, Kraft JN, Lynde CW. Topical treatments for melasma and post-inflammatory hyperpigmentation. Skin Thera Lett 2006;11:1-6.
4. Anisha BP. Postinflammatory hyperpigmentation. Review of pathogenesis, prevention, and treatment. Pigment Int 2014;1:59-69.
5. Jiao J. Polyoxy ethylated nonionic surfactants and their applications in topical ocular drug delivery. Adv Drug Delivery Rev 2008;60:1663-73.
6. Madhav NV, Saini A. Niosomes a novel drug delivery system. Int J Res Pharm Chem 2011;1:498-511.
7. Nagalakshmi S, Damodharan N, Thanka J, Seethalakshmi S. Niosomes in ocular drug delivery system. A review of magic targeted drug delivery. Int J Pharm Sci Rev Res 2015;32:61-6.
8. Kumar BS, Krishna R, Lakshmi PS, Vasudev DT, Nair SC. Formulation and evaluation of niosomal suspension of cefixime. Asian J Pharm Clin Res 2017;10:194-201.
9. Kopermsuba P, Mayena V, Warin C. Potential use of niosomes for encapsulation of nisin and EDTA and their antibacterial activity enhancement. Food Res Int 2011;44:605–12.
10. Paul S, Mondol R, Ranjit S, Maiti S. Antiglaucomatic niosomal system: recent trend in ocular drug delivery research. Int J Pharm Pharm Sci 2010;2:15-8.
11. Draelos ZD. Skin lightening preparations and the hydroquinone controversy. Dermatol Ther 2007;20:308-13.
12. Céline C, Laurence C. Overview of skin whitening agents: drugs and cosmetic products. Cosmetics J 2016;3:1-16.
13. Sharma B, Sharma A. Future prospect of nanotechnology in development of anti-aging formulations. Int J Pharm Pharm Sci 2012;4:57-66.
14. Agarwal R, Katar OP, Vyas SP. Preparation and in vitro evaluation of liposomal/niosomal delivery systems for antipsoriatic drug dithranol. Int J Pharm 2001;228:43-52.
15. US Patent-Meybeck, United States patent: patent number 5279834;1994.
16. Manosroi A, Y Vongtrakfui P, Manosroi J, Sakai H, Sugawara F, Yuasa M, et al. Characterization of vesicles prepared with various non-ionic surfactants mixed with cholesterol. Colloid Surf B 2003;30:129-38.
17. Bansal S, Aggarwal G, Chandel P, Harikumar SL. Design and development of cefdinir niosomes for oral delivery. Pharm Bioallied Sci 2013;5:318–25.
18. Mokhtar M, Amour OA, Hammed MA, Megrab NA. Effect of some formulation parameters on flurbiprofen encapsulation and release rates of niosomes prepared from proniosomes. Int J Pharm 2008;361:104-11.
19. Akhilesh D, Prabhakara P. Development and investigation of niosomes of brimonidine tartrate and timolol maleate for the treatment of glaucoma. Int J PharmTech Res 2014;6:942-50.
20. Sezgin Bayinder Z, Yoksel N. Investigation of formulation variables and excipient interaction on the production of niosomes. AAPS PharmSciTech 2012;13:826–35.
21. Ruckmani K, Sankar V, Sivakumar M. Tissue distribution, pharmacokinetics and stability studies of zidovudine delivered by niosomes and proniosomes. J Biomed Nanotechnol 2010;6:43-51.
22. Abdallah AM. Controlled release formulations of certain anti-inflammatory drugs. M Sc Zagazig, University; 2005.
23. Larrucea E, Arellano A, Santoyo S, Ygartua P. Interaction of tenoxicam with cyclodextrins and its influence on the in vitro percutaneous penetration of the drug. Drug Dev Ind Pharm 2001;27:251-60.
24. Fergani AM. Topical permeation characteristics of diclofenac sodium from Na CMC gels in comparison with conventional gel formulation. Drug Dev Ind Pharm 2001;27:1083-97.
25. Shivhare UD, Jain KB, Mathur VB, Bhusari KP, Roy AA, Sharad. Formulation development and evaluation of diclofenac sodium gel using water-soluble polyacrylamide polymer. Digest J Nanomat Biostruct 2009;4:285-90.
26. Shinde U, Pokharkar S, Modani S. Design and evaluation of microemulsion gel system of nadifloxacin. Indian J Pharm Sci 2012;74:237–47.
27. Charyulu RN, Harish NM, Mohammed GA, Prabhu P, Amith KS, Subrahmanyam EV. Formulation and in vitro evaluation of in situ gels containing secnidazole for vaginitis. Yakugakuzasshi 2009;129:569-74.
28. Sammour OA, Marzouk MA, Ramadan AA, Shawky SM. In vitro permeation and pharmaco-dynamic properties of gel formulations containing tenoxicam entrapped noisome. J Life Med 2013;1:1-10.
29. Pandya AG, Hynan LS, Bhore R. Reliability assessment and validation of the melasma area and severity index (MASI) and a new modified MASI scoring method. J Am Acad Dermatol 2011;64:78-83.
30. Majid I, Haq I, Imran S, Keen A, Aziz K, Arif T. Proposing melasma severity index: a new, more practical, office-based scoring system for assessing the severity of melasma. Indian J Dermatol 2016;61:39-44.
31. Eilers S, Bach DQ, Gaber R, Blatt H, Guevara Y, Nitsche K, et al. Accuracy of self-report in assessing fitzpatrick skin phototypes I through VI. JAMA Dermatol 2013;149:1289-94.
32. Sachdeva S. Fitzpatrick skin typing. Applications in dermatology. Indian J Dermatol Venereol Leprol 2009;75:93-6.
33. Popli H, Nair MS. Niosomal delivery of tenoxicam. Ind J Pharm Sci 1996;58:163-6.
34. El-Megrab NA, Hanan M, El-Nahas HM, Balata GF. Formulation and evaluation of meloxicam gels for topical administration. Saudi Pharm J 2006;14:155-62.
35. Yogeshwar GB, Vandana BP. Formulation of meloxicam gel for topical application: in vitro and in vivo evaluation. Acta Pharm 2010;60:153–63.
36. Perez M, Luke J, Rossi A. Melasma in latin americans. J Drugs Dermatol 2011;10:517-23.
37. Katiyar S, Saify K, Rai M. A systemic review on melasma. Int J Curr Bio Med Sci 2011;1:63-8.
38. Gajjala S, Ali SY, Chowdary N, Harshini S. The comparative study of hydroquinone and kojic acid in the treatment of melasma. IOSR J Dental Med Sci 2016;15:1-5.
39. Haddad AL, Matos LF, Brunstein F, Ferreira LM. A clinical prospective, randomized, double-blind trial comparing skin whitening complex with hydroquinone vs. placebo in the treatment of melasma. Int J Dermatol 2003;42:153-6.
40. Samreen R, Iftikhar U, Rani Z, Hussain I. Comparison of efficacy and safety of topical hydroquinone 2% and oral tranexamic acid 500 mg in patients of melasma. J Pakistan Assoc Dermatol 2017;27:204-13.
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AMMAR, A. A., SALEM, H. A., ELADAWY, S. A., ELSAMAD, Z. I. A., & KOHAF, N. A. (2020). DEVELOPMENT AND CLINICAL EVALUATION OF TOPICAL HYDROQUINONE NIOSOMAL GEL FORMULATION FOR THE TREATMENT OF MELASMA. International Journal of Applied Pharmaceutics, 12(4), 228-236. https://doi.org/10.22159/ijap.2020v12i4.34304
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