Generic placeholder image

Current Drug Therapy

Editor-in-Chief

ISSN (Print): 1574-8855
ISSN (Online): 2212-3903

Research Article

Formulation Development and Evaluation of Apremilast Nanoemulgel for Enhancing Permeability

Author(s): Neelam Patel*, Sunita Chaudhary and Ankit Chaudhary

Volume 18, Issue 2, 2023

Published on: 23 January, 2023

Page: [132 - 150] Pages: 19

DOI: 10.2174/1574885518666230103152130

Price: $65

Abstract

Background: Oral apremilast, a selective phosphodiesterase-4 inhibitor, is effective in the treatment of moderate to severe plaque psoriasis and acute psoriatic arthritic disease. According to BCS categorization, it is a class IV medication, which denotes low solubility and lesser permeability through the skin.

Objective: The objective of the research is to develop a nanoemulsion that will increase apremilast’s skin permeability. Utilizing a simplex lattice design, an optimised nanoemulsion has been developed, and then transformed into a gel form and created as a nanoemulgel.

Methods: The nanoemulsion was developed by selecting the oil, surfactant, co-surfactant, and cosolvent, in that order, based on the solubility study, and was then evaluated based on various criteria. Different grades and concentrations of carbopol polymer were used to make nanoemulgel, which was then tested for physicochemical parameters like pH, viscosity, spreadability, extrudability, percentage of drug content, percentage of drug diffusion, skin permeation, and skin retention. For skin irritancy tests, male Wistar albino rats weighing between 200 and 250 g were used to find out how likely it was that apremilast-loaded nanoemulgel would cause skin irritation.

Results: The nanoemulsion formulation A5 containing 10% Captex 355 and 40% Smix in a 3:1 ratio of Cremophore RH 40: Labrafil showed the smallest particle size and greatest drug diffusion. In comparison to other formulations of emulgel, the 0.75 % concentration of carbopol 940 produced the best results.

Conclusion: A stable nanoemulgel system with apremilast loaded was created, and a number of process factors were assessed. The optimised batch produced repeatable results when evaluated, exhibited no skin irritation, and was shown to be stable after three months at ambient conditions of temperature and humidity.

Keywords: Nanoemulgel, apremilast, carbopol, psoriasis, simple lattice design, skin permeation.

Graphical Abstract
[1]
Pradhan M, Singh D, Singh MR. Novel colloidal carriers for psoriasis: Current issues, mechanistic insight and novel delivery approaches. J Control Release 2013; 170(3): 380-95.
[http://dx.doi.org/10.1016/j.jconrel.2013.05.020] [PMID: 23770117]
[2]
Puig L, Julià A, Marsal S. The pathogenesis and genetics of psoriasis. Actas Dermo-Sifiliográficas (English Edition) 2014; 105(6): 535-45.
[http://dx.doi.org/10.1016/j.adengl.2014.05.013] [PMID: 23369832]
[3]
Kaltwasser JP, Nash P, Gladman D, et al. Efficacy and safety of leflunomide in the treatment of psoriatic arthritis and psoriasis: A multinational, double-blind, randomized, placebo-controlled clinical trial. Arthritis Rheum 2004; 50(6): 1939-50.
[http://dx.doi.org/10.1002/art.20253] [PMID: 15188371]
[4]
Dogra S, Afra TP, Razmi TM. Apremilast in psoriasis and beyond: Big hopes on a small molecule. Indian Dermatol Online J 2019; 10(1): 1-12.
[http://dx.doi.org/10.4103/idoj.IDOJ_437_18] [PMID: 30775293]
[5]
Butler T, Maravent S, Boisselle J, Valdes J, Fellner C. A review of 2014 cancer drug approvals, with a look at 2015 and beyond. P&T 2015; 40(3): 191-205.
[PMID: 25798040]
[6]
Ighani A, Georgakopoulos JR, Zhou LL, Walsh S, Shear N, Yeung J. Efficacy and safety of Apremilast monotherapy for moderate to severe psoriasis: Retrospective study. J Cutan Med Surg 2018; 22(3): 290-6.
[http://dx.doi.org/10.1177/1203475418755982] [PMID: 29373924]
[7]
Abdulrahim H, Thistleton S, Adebajo AO, Shaw T, Edwards C, Wells A. Apremilast: A PDE4 inhibitor for the treatment of psoriatic arthritis. Expert Opin Pharmacother 2015; 16(7): 1099-108.
[http://dx.doi.org/10.1517/14656566.2015.1034107] [PMID: 25864487]
[8]
Edwards CJ, Blanco FJ, Crowley J, et al. Apremilast, an oral phosphodiesterase 4 inhibitor, in patients with psoriatic arthritis and current skin involvement: A phase III, randomised, controlled trial (PALACE 3). Ann Rheum Dis 2016; 75(6): 1065-73.
[http://dx.doi.org/10.1136/annrheumdis-2015-207963] [PMID: 26792812]
[9]
Bakshi H, Nagpal M, Singh M, Dhingra GA, Aggarwal G. Treatment of psoriasis: A comprehensive review of entire therapies. Curr Drug Saf 2020; 15(2): 82-104.
[http://dx.doi.org/10.2174/22123911MTAziOTU84] [PMID: 31994468]
[10]
Nastiti C, Ponto T, Abd E, Grice J, Benson H, Roberts M. Topical nano and microemulsions for skin delivery. Pharmaceutics 2017; 9(4): 37.
[http://dx.doi.org/10.3390/pharmaceutics9040037] [PMID: 28934172]
[11]
Patel MR, Patel RB, Parikh JR, Patel BG. Novel microemulsion-based gel formulation of tazarotene for therapy of acne. Pharm Dev Technol 2016; 21(8): 921-32.
[http://dx.doi.org/10.3109/10837450.2015.1081610] [PMID: 26334480]
[12]
Mu H, Holm R, Müllertz A. Lipid-based formulations for oral administration of poorly water-soluble drugs. Int J Pharm 2013; 453(1): 215-24.
[http://dx.doi.org/10.1016/j.ijpharm.2013.03.054] [PMID: 23578826]
[13]
Münch S, Wohlrab J, Neubert RHH. Dermal and transdermal delivery of pharmaceutically relevant macromolecules. Eur J Pharm Biopharm 2017; 119: 235-42.
[http://dx.doi.org/10.1016/j.ejpb.2017.06.019] [PMID: 28647443]
[14]
Kulkarni P, Deshpande A. Analytical methods for determination of Apremilast from bulk, dosage form and biological fluids: A critical review. Crit Rev Anal Chem 2021; 51(3): 258-67.
[http://dx.doi.org/10.1080/10408347.2020.1718481] [PMID: 32024370]
[15]
Singh G, Pai RS. Trans -resveratrol self-nano-emulsifying drug delivery system (SNEDDS) with enhanced bioavailability potential: Optimization, pharmacokinetics and in situ single pass intestinal perfusion (SPIP) studies. Drug Deliv 2015; 22(4): 522-30.
[http://dx.doi.org/10.3109/10717544.2014.885616] [PMID: 24512464]
[16]
Pund S, Thakur R, More U, Joshi A. Lipid based nanoemulsifying resveratrol for improved physicochemical characteristics, in vitro cytotoxicity and in vivo antiangiogenic efficacy. Colloids Surf B Biointerfaces 2014; 120: 110-7.
[http://dx.doi.org/10.1016/j.colsurfb.2014.05.016] [PMID: 24905685]
[17]
Amra K, Momin M. Formulation evaluation of ketoconazole microemulsion‐loaded hydrogel with nigella oil as a penetration enhancer. J Cosmet Dermatol 2019; 18(6): 1742-50.
[http://dx.doi.org/10.1111/jocd.12945] [PMID: 30980617]
[18]
Espitia PJP, Fuenmayor CA, Otoni CG. Nanoemulsions: Synthesis, characterization, and application in bio-based active food packaging. Compr Rev Food Sci Food Saf 2019; 18(1): 264-85.
[http://dx.doi.org/10.1111/1541-4337.12405] [PMID: 33337016]
[19]
Oza N, Sagar S, Khodakiya A. Use of simplex lattice design in development of oral self-nanoemulsifying drug delivery system containing rosuvastatin calcium. Int J Appl Pharm 2020; 12(3): 40-7.
[http://dx.doi.org/10.22159/ijap.2020v12i3.34358]
[20]
Tandel H, Upadhay M, Raval K, Nayani A. Preparation and evaluation of cilnidipine microemulsion. J Pharm Bioallied Sci 2012; 4(5) (Suppl. 1): 114.
[http://dx.doi.org/10.4103/0975-7406.94162] [PMID: 23066184]
[21]
Date AA, Nagarsenker MS. Design and evaluation of microemulsions for improved parenteral delivery of propofol. AAPS PharmSciTech 2008; 9(1): 138-45.
[http://dx.doi.org/10.1208/s12249-007-9023-7] [PMID: 18446474]
[22]
Barot BS, Parejiya PB, Patel HK, Gohel MC, Shelat PK. Microemulsion-based gel of terbinafine for the treatment of onychomycosis: Optimization of formulation using D-optimal design. AAPS PharmSciTech 2012; 13(1): 184-92.
[http://dx.doi.org/10.1208/s12249-011-9742-7] [PMID: 22187363]
[23]
Choudhury H, Gorain B, Pandey M, et al. Recent update on nanoemulgel as topical drug delivery system. J Pharm Sci 2017; 106(7): 1736-51.
[http://dx.doi.org/10.1016/j.xphs.2017.03.042] [PMID: 28412398]
[24]
Butani D, Yewale C, Misra A. Amphotericin B topical microemulsion: Formulation, characterization and evaluation. Colloids Surf B Biointerfaces 2014; 116: 351-8.
[http://dx.doi.org/10.1016/j.colsurfb.2014.01.014] [PMID: 24521698]
[25]
Pople PV, Singh KK. Development and evaluation of topical formulation containing solid lipid nanoparticles of vitamin A. AAPS PharmSciTech 2006; 7(4): E63-9.
[http://dx.doi.org/10.1208/pt070491] [PMID: 17285742]
[26]
Abu-Elyazid S, Kassem A, Samy A, Gomaa M. Evaluation of skin permeation and pharmacological effects of tenoxicam nanoemulsión in topical formulations. Asian J PharmHealth Sci 2011; 1(3): 99-105.
[27]
van der Fits L, Mourits S, Voerman JSA, et al. Imiquimod-induced psoriasis-like skin inflammation in mice is mediated via the IL-23/IL-17 axis. J Immunol 2009; 182(9): 5836-45.
[http://dx.doi.org/10.4049/jimmunol.0802999] [PMID: 19380832]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy