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

Abstract

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.


Citation:

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.

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Reference

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

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