A co-additive nanoemulgel formulation of tretinoin and curcumin: Formulation and optimization

Parmita Phaugat Suchita Nishal Rohit Dutt Aparna Khansili   

Open Access   

Published:  Jun 16, 2022


Tretinoin (TRT), a natural all-trans retinoic acid occurring retinoid metabolite, belongs to the first generation of retinoids used to treat various skin ailments, like acne vulgaris and skin ageing and psoriasis. In this study, a combination of drugs using TRT and curcumin (CUR) nanoemulsion (NE) is fabricated, and is further added to a gel formulation to boost the efficacy and stability of the topical formulation. A high-energy sonication technique was used in the NE fabrication, and optimization was carried out using the Box–Behnken design. The TRT–CUR–NEs were found to have a mean particle size, zeta potential, and PDI of 77.6 ± 2.1 nm, −20.7 ± 4.4 mV, and 0.268 ± 0.029, respectively. The optimized formulation of TRT–CUR–NE has a % entrapment efficiency of 85.92% ± 2.6% and 88.31% ± 3.2% for TRT and CUR, respectively, and a % loading efficiency of 19.6% ± 1.2% and 18.7% ± 2.5%, respectively, for TRT and CUR, respectively. The in vitro release profile displayed % cumulative drug release of 28.64% ± 0.31%, 80.32% ± 0.42%, and 89.64% ± 0.97% after 24 hours for plain gel, TRT–CUR–NE, and TRT–CUR–nanoemulgel, respectively.

Keyword:     Tretinoin curcumin nanoemulsion nanoemulgel Box–Behnken design.


Phaugat P, Nishal S, Dutt R, Khansili A. A co-additive Nanoemulgel formulation of Tretinoin and Curcumin: Formulation and optimization. J Appl Pharm Sci, 2022. Online First.

Copyright: © The Author(s). This is an open-access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

HTML Full Text


Ahmad J, Gautam A, Komath S, Bano M, Garg A, Jain K. Topical nano-emulgel for skin disorders: formulation approach and characterization. Recent Pat Antiinfect Drug Discov, 2019; 14(1):36-48. https://doi.org/10.2174/1574891X14666181129115213

Algahtani MS, Ahmad MZ, Ahmad J. Nanoemulgel for improved topical delivery of retinyl palmitate: formulation design and stability evaluation. Nanomaterials, 2020; 10(5):848. https://doi.org/10.3390/nano10050848

Ali I, Shah LA. Rheological investigation of the viscoelastic thixotropic behavior of synthesized polyethylene glycol-modified polyacrylamide hydrogels using different accelerators. Polym Bull, 2021; 78(3):1275-91. https://doi.org/10.1007/s00289-020-03163-x

Aithal GC, Narayan R, Nayak UY. Nanoemulgel: a promising phase in drug delivery. Curr Pharm Des, 2020; 26(2):279-91. https://doi.org/10.2174/1381612826666191226100241

Artiga-Artigas M, Lanjari-Pérez Y, Martín-Belloso O. Curcuminloaded nanoemulsions stability as affected by the nature and concentration of surfactant. Food Chem, 2018; 266:466-74. https://doi.org/10.1016/j.foodchem.2018.06.043

Azami SJ, Teimouri A, Keshavarz H, Amani A, Esmaeili F, Hasanpour H, Elikaee S, Salehiniya H, Shojaee S. Curcumin nanoemulsion as a novel chemical for the treatment of acute and chronic toxoplasmosis in mice. Int J Nanomedicine, 2018; 13:7363. https://doi.org/10.2147/IJN.S181896

Batra H, Pawar S, Bahl D. Curcumin in combination with anticancer drugs: a nanomedicine review. Pharmacol Res, 2019; 139:91-105. https://doi.org/10.1016/j.phrs.2018.11.005

Beg S, Swain S, Rahman M, Hasnain MS, Imam SS. Application of design of experiments (DoE) in pharmaceutical product and process optimization. In: Pharmaceutical quality by design. Elsevier, pp 43-64, 2019. https://doi.org/10.1016/B978-0-12-815799-2.00003-4

Bhoop BS, Beg S, Raza K. Developing "optimized" drug products employing "designed" experiments. Chem Ind Digest, 2013; 23:70-6.

Campani V, Biondi M, Mayol L, Cilurzo F, Pitaro M, De Rosa G. Development of nanoemulsions for topical delivery of vitamin K1. Int J Pharm, 2016; 511(1):170-7. https://doi.org/10.1016/j.ijpharm.2016.07.004

Chandrashekhar B, Anitha M, Ruparelia M, Vaidya P, Aamir R, Shah S, Thilak S, Aurangabadkar S, Pal S, Saraswat A, Sanmukhani JJ. Tretinoin nanogel 0.025% versus conventional gel 0.025% in patients with acne vulgaris: a randomized, active controlled, multicentre, parallel group, phase IV clinical trial. J Clin Diagn Res, 2015; 9(1):WC04. https://doi.org/10.7860/JCDR/2015/10663.5469

Chen H, Khemtong C, Yang X, Chang X, Gao J. Nanonization strategies for poorly water-soluble drugs. Drug Discov Today, 2011; 16(7- 8):354-60. https://doi.org/10.1016/j.drudis.2010.02.009

Chen J, Ma Y, Tao Y, Zhao X, Xiong Y, Chen Z, Tian Y. Formulation and evaluation of a topical liposomal gel containing a combination of zedoary turmeric oil and tretinoin for psoriasis activity. J Liposome Res, 2020; 31(2):1-15. https://doi.org/10.1080/08982104.2020.1748646

Costa P, Lobo JMS. Modeling and comparison of dissolution profiles. Eur J Pharm Sci, 2001; 13(2):123-33. https://doi.org/10.1016/S0928-0987(01)00095-1

Dhawan B, Aggarwal G, Harikumar S. Enhanced transdermal permeability of piroxicam through novel nanoemulgel formulation. Int J Pharm Investig, 2014; 4(2):65. https://doi.org/10.4103/2230-973X.133053

Diwan R, Khan S, Ravi PR. Comparative study of cilnidipine loaded PLGA nanoparticles: process optimization by DoE, physicochemical characterization and in vivo evaluation. Drug Deliv Transl Res, 2020; 10(5):1442-58. https://doi.org/10.1007/s13346-020-00732-5

Desam NR, Al-Rajab AJ. The importance of natural products in cosmetics. In: Bioactive natural products for pharmaceutical applications, Springer, pp 643-85, 2021. https://doi.org/10.1007/978-3-030-54027-2_19

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 J Pharm Sci, 2018; 4(1):18-28. https://doi.org/10.1016/j.fjps.2017.07.003

Gadkari P, Patil P, Saudagar R. Formulation, development and evaluation of topical nanoemulgel of tolnaftate. J drug deliv ther, 2019; 9(2- s):208-13.

Ghica MV, Hîrj?u M, Lupuleasa D, Dinu-Pîrvu CE. Flow and thixotropic parameters for rheological characterization of hydrogels. Molecules, 2016; 21(6):786. https://doi.org/10.3390/molecules21060786

Gillis JC, Goa KL. Tretinoin. Drugs, 1995; 50(5):897-923. Heng M. Topical curcumin: a review of mechanisms and uses in dermatology. Int J Dermatol Clin Res, 2017; 3(1):010-7. https://doi.org/10.2165/00003495-199550050-00008

Hussain Z, Thu HE, Ng SF, Khan S, Katas H. Nanoencapsulation, an efficient and promising approach to maximize wound healing efficacy of curcumin: a review of new trends and state-of-the-art. Colloids Surf B Biointerfaces, 2017; 150:223-41. https://doi.org/10.1016/j.colsurfb.2016.11.036

Jain K, Sood S, Gowthamarajan K. Optimization of artemetherloaded NLC for intranasal delivery using central composite design. Drug deliv, 2015; 22(7):940-54. https://doi.org/10.3109/10717544.2014.885999

Jaiswal M, Dudhe R, Sharma P. Nanoemulsion: an advanced mode of drug delivery system. Biotech, 2015; 5(2):123-7. https://doi.org/10.1007/s13205-014-0214-0

Karri VNR, Raman SK, Kuppusamy G, Mulukutla S, Ramaswamy S, Malayandi R. Terbinafine hydrochloride loaded nanoemulsion based gel for topical application. J Pharm Investig, 2015; 45(1):79-89. https://doi.org/10.1007/s40005-014-0149-9

Kim A, Weinkle SH. Cosmeceuticals using vitamin A and its derivatives plus new delivery methods for them. In: Cosmeceuticals, Karger Publishers, pp 26-37, 2021. https://doi.org/10.1159/000491843

Kohli K, Ali J, Ansari M, Raheman Z. Curcumin: a natural antiinflammatory agent. Indian J Pharmacol, 2005; 37(3):141. https://doi.org/10.4103/0253-7613.16209

Lai F, Pireddu R, Corrias F, Fadda AM, Valenti D, Pini E, Sinico C. Nanosuspension improves tretinoin photostability and delivery to the skin. Int J Pharm, 2013; 458(1):104-9. https://doi.org/10.1016/j.ijpharm.2013.10.007

Lokhandwala H, Deshpande A, Deshpande S. Kinetic modeling and dissolution profiles comparison: an overview. Int J Pharm Bio Sci, 2013; 4(1):728-73.

Ma Q, Zhang J, Lu B, Lin H, Sarkar R, Wu T, Li X. Nanoemulgel for improved topical delivery of desonide: formulation design and characterization. AAPS Pharm Sci Tech, 2021; 22(5):1-14. https://doi.org/10.1208/s12249-021-02035-5

Md S, Alhakamy NA, Aldawsari HM, Kotta S, Ahmad J, Akhter S, Shoaib Alam M, Khan MA, Awan Z, Sivakumar PM. Improved analgesic and anti-inflammatory effect of diclofenac sodium by topical nanoemulgel: formulation development-in vitro and in vivo studies. J Chem, 2020; 2020. https://doi.org/10.1155/2020/4071818

Ojha B, Jain VK, Gupta S, Talegaonkar S, Jain K. Nanoemulgel: a promising novel formulation for treatment of skin ailments. Polym Bull, 2021:1-25. https://doi.org/10.1007/s00289-021-03729-3

Rahman SA, Abdelmalak NS, Badawi A, Elbayoumy T, Sabry N, Ramly AE. Formulation of tretinoin-loaded topical proniosomes for treatment of acne: in-vitro characterization, skin irritation test and comparative clinical study. Drug Deliv, 2015; 22(6):731-9. https://doi.org/10.3109/10717544.2014.896428

Sahu S, Katiyar SS, Kushwah V, Jain S. Active natural oil-based nanoemulsion containing tacrolimus for synergistic antipsoriatic efficacy. Nanomedicine, 2018; 13(16):1985-98. https://doi.org/10.2217/nnm-2018-0135

Samaha D, Shehayeb R, Kyriacos S. Modeling and comparison of dissolution profiles of diltiazem modified-release formulations. Dissolution Technol, 2009; 16(2):41-6. https://doi.org/10.14227/DT160209P41

Saani SM, Abdolalizadeh J, Heris SZ. Ultrasonic/sonochemical synthesis and evaluation of nanostructured oil in water emulsions for topical delivery of protein drugs. Ultrason Sonochem, 2019; 55:86-95. https://doi.org/10.1016/j.ultsonch.2019.03.018

Schreiner TB, Santamaria-Echart A, Ribeiro A, Peres AM, Dias MM, Pinho SP, Barreiro MF. Formulation and optimization of nanoemulsions using the natural surfactant saponin from quillaja bark. Molecules, 2020; 25(7):1538. https://doi.org/10.3390/molecules25071538

Singh B, Saini S, Lohan S, Beg S. Systematic development of nanocarriers employing quality by design paradigms. In: Nanotechnologybased approaches for targeting and delivery of drugs and genes, Elsevier, pp 110-48, 2017. https://doi.org/10.1016/B978-0-12-809717-5.00003-8

Thakur A, Walia MK, Kumar S. Nanoemulsion in enhancement of bioavailability of poorly soluble drugs: a review. Pharmacophore, 2013; 4(1):15-25.

Voorhees J. Clinical effects of long-term therapy with topical tretinoin and cellular mode of action. J Int Med Res, 1990; 18:26C-8C.

Waghule T, Gorantla S, Rapalli VK, Shah P, Dubey SK, Saha RN, Singhvi G. Emerging trends in topical delivery of Curcumin through lipid nanocarriers: effectiveness in skin disorders. AAPS Pharm Sci Tech, 2020; 21(7):1-12. https://doi.org/10.1208/s12249-020-01831-9

Yeo E, Chieng CJY, Choudhury H, Pandey M, Gorain B. Tocotrienols-rich naringenin nanoemulgel for the management of diabetic wound: fabrication, characterization and comparative in vitro evaluations. Curr Res Pharmacolo Drug Dis, 2021; 2:100019. https://doi.org/10.1016/j.crphar.2021.100019

Zhang Z, McClements DJ. Overview of nanoemulsion properties: stability, rheology, and appearance. In: Nanoemulsions, Elsevier, pp 21-49, 2018. https://doi.org/10.1016/B978-0-12-811838-2.00002-3

Article Metrics

1 Absract views 0 PDF Downloads 1 Total views

   Abstract      Pdf Download

Related Search

By author names

Citiaion Alert By Google Scholar

Name Required
Email Required Invalid Email Address

Comment required