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Pharmaceutical Nanotechnology

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Research Article

Nanostructured Etodolac Carriers in Transdermal Gel: Optimization and Characterization

Author(s): Poonam Patil* and Atul Shirkhedkar

Volume 11, Issue 3, 2023

Published on: 01 March, 2023

Page: [276 - 293] Pages: 18

DOI: 10.2174/2211738511666230111110340

Price: $65

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Abstract

Aims: To optimize, formulate, and evaluate a Nanostructured Lipid Carrier (NLC) based transdermal gel of Etodolac (ETD).

Objective: To avoid issues of conventional route ETD administration like first pass metabolism, gastric ulceration, hemorrhage, and being a class-II drug with less solubility. A transdermal gel of nanostructured lipid carrier for ETD has been developed. Formulation will execute faster onset of action, increased penetration, permeation with extended release of the drug for a longer duration.

Methods: A central composite 32 factorial design is used to plan experiments. NLCs are prepared by the method of melt emulsification and ultrasonication. Compritol 888ATO and Miglyol are used as solid and liquid lipid phases. Surfactant Pluronic F68 showed a significant effect on particle size, entrapment efficiency, and drug release. Particle size characterized using photon correlation spectroscopy and scanning electron microscopy. Cumulative drug release studied using an artificial diffusion cell and a dialysis membrane. A skin permeation study was performed using goat skin at 32°C ± 0.5°C. The efficacy of the NLC gel was verified using a pharmacodynamic study followed by stability study for 3 and 6 months.

Results: The optimized batch of ETD NLC found spherical with a 241.3 nm particle size with 0.392 PDI,-29 mV zeta potential. Entrapment efficiency and cumulative drug release were found to be 64.21 ± 1.23% and 70.12 ± 2.10% (after 12 hours), respectively. All batches followed zeroorder drug release kinetics and non-Fickian (Super Case II transport) with 0.1619 mg/cm2/hr transdermal flux. The NLC gel of ETD showed a quick onset and lengthened therapeutic activity until 24 hours compared to the micellar ETD gel.

Conclusion: Etodolac NLC batch successfully optimized using central composite design. The relationships between the components of the NLC-total lipid:drug and surfactant-and the outcomes- particle size,%entrapment and% drug release-were better understood by examining several contour plots. The results of the experimental and predicted formulations were found to be in good agreement with slight bias, demonstrating the reliability of the optimization process.

Keywords: Melt emulsification and ultrasonication, optimization, compritol 888ATO, zeta potential, carrageenan, surface response plot, nanostrucured lipid carrier (NLC), transdermal gel, carbopol.

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[1]
Müller RH, Radtke M, Wissing SA. Nanostructured lipid matrices for improved microencapsulation of drugs. Int J Pharm 2002; 242(1-2): 121-8.
[http://dx.doi.org/10.1016/S0378-5173(02)00180-1] [PMID: 12176234]
[2]
Shidhaye S, Vaidya R, Sutar S, Patwardhan A, Kadam V. Solid lipid nanoparticles and nanostructured lipid carriers--innovative generations of solid lipid carriers. Curr Drug Deliv 2008; 5(4): 324-31.
[http://dx.doi.org/10.2174/156720108785915087] [PMID: 18855604]
[3]
M¨uller RH, Wissing SA, Kayser O. Solid lipid nanoparticles for parenteral drug delivery. Adv Drug Deliv Rev 2004; 56: 1257-72.
[4]
Shirkhedkar AA, Patil PS. Breakthroughs in transdermal nanostructured lipid carrier drug delivery systems. Int J Pharm Sci Res 2021; 12(3): 1352-66.
[5]
Müller RH, Radtke M, Wissing SA. Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) in cosmetic and dermatological preparations. Adv Drug Deliv Rev 2002; 54 (Suppl. 1): S131-55.
[http://dx.doi.org/10.1016/S0169-409X(02)00118-7] [PMID: 12460720]
[6]
Pardeike J, Hommoss A, Müller RH. Lipid nanoparticles (SLN, NLC) in cosmetic and pharmaceutical dermal products. Int J Pharm 2009; 366(1-2): 170-84.
[http://dx.doi.org/10.1016/j.ijpharm.2008.10.003] [PMID: 18992314]
[7]
Garcês A, Amaral MH, Sousa Lobo JM, Silva AC. Formulations based on solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) for cutaneous use: A review. Eur J Pharm Sci 2018; 112: 159-67.
[http://dx.doi.org/10.1016/j.ejps.2017.11.023] [PMID: 29183800]
[8]
Haider M, Abdin SM, Kamal L, Orive G. Nanostructured lipid carriers for delivery of chemotherapeutics: A review. Pharmaceutics 2020; 12(3): 288.
[http://dx.doi.org/10.3390/pharmaceutics12030288] [PMID: 32210127]
[9]
Kumar SS, Masilamani K, Srinivas SS, Ravichandiran V. Proceedings of the International Conference on Biotechnology and Pharmaceutical Sciences. Bangkok, Thailand. 2011.
[10]
Gill V, Nanda A. Preparation and characterization of etodolac bearing emulsomes. Int J App Pharm 2020; 5: 166-72.
[http://dx.doi.org/10.22159/ijap.2020v12i5.38842]
[11]
Salah S, Mahmoud AA, Kamel AO. Etodolac transdermal cubosomes for the treatment of rheumatoid arthritis: Ex vivo permeation and in vivo pharmacokinetic studies. Drug Deliv 2017; 24(1): 846-56.
[http://dx.doi.org/10.1080/10717544.2017.1326539] [PMID: 28535740]
[12]
Agis F, Berner KB. Transdermal delivery of drugs. CRS Press. ISBN-10: 0849364833. ISBN-13:978-0849364839 1986; 1: 5-57.
[13]
Mehnert W, Mäder K. Solid lipid nanoparticles. Adv Drug Deliv Rev 2012; 64: 83-101.
[http://dx.doi.org/10.1016/j.addr.2012.09.021] [PMID: 11311991]
[14]
Petersen S, Ulrich J. Role of emulsifiers in emulsion technology and emulsion crystallization. Chem Eng Technol 2013; 36(3): 398-402.
[http://dx.doi.org/10.1002/ceat.201200648]
[15]
Bhattacharyya SS, Rana DS, Bhattacharyya SN. Determination of heat of formation of associated systems by calorimetry. J Indian Chem Soc 1997; 74(2): 103-7.
[http://dx.doi.org/10.5281/zenodo.5875144]
[16]
Behrend O, Ax K, Schubert H. Influence of continuous phase viscosity on emulsification by ultrasound. Ultrason Sonochem 2000; 7(2): 77-85.
[http://dx.doi.org/10.1016/S1350-4177(99)00029-2] [PMID: 10769874]
[17]
Karbstein H, Schubert H. Developments in the continuous mechanical production of oil-in-water macro-emulsions. Chem Eng Process 1995; 34(3): 205-11.
[http://dx.doi.org/10.1016/0255-2701(94)04005-2]
[18]
Stang M, Karbstein H, Schubert H. Adsorption kinetics of emulsifiers at oil—water interfaces and their effect on mechanical emulsification. Chem Eng Process 1994; 33(5): 307-11.
[http://dx.doi.org/10.1016/0255-2701(94)02000-0]
[19]
Hill WJ, Hunter WG. A review of response surface methodology: A literature survey. Technometrics 1966; 8(4): 571-90.
[http://dx.doi.org/10.2307/1266632]
[20]
Thakkar H, Desai J, Parmar M. Application of Box-Behnken design for optimization of formulation parameters for nanostructured lipid carriers of candesartan cilexetil. Asian J Pharm 2014; 8(2): 81-9.
[http://dx.doi.org/10.4103/0973-8398.134921]
[21]
Joshi M, Patravale V. Nanostructured lipid carrier (NLC) based gel of celecoxib. Int J Pharm 2008; 346(1-2): 124-32.
[http://dx.doi.org/10.1016/j.ijpharm.2007.05.060] [PMID: 17651933]
[22]
Thatipamula R, Palem C, Gannu R, Mudragada S, Yamsani M. Formulation and in vitro characterization of domperidone loaded solid lipid nanoparticles and nanostructured lipid carriers. Daru 2011; 19(1): 23-32.
[PMID: 22615636]
[23]
Bhalekar MR, Pokharkar V, Madgulkar A, Patil N, Patil N. Preparation and evaluation of miconazole nitrate-loaded solid lipid nanoparticles for topical delivery. AAPS PharmSciTech 2009; 10(1): 289-96.
[http://dx.doi.org/10.1208/s12249-009-9199-0] [PMID: 19294517]
[24]
Khurana S, Bedi PMS, Jain NK. Development of nanostructured lipid carriers (NLC) for controlled delivery of meloxicam. Int J Biomed Nanosci Nanotechnol 2010; 1((2/3/4): 247-66.
[http://dx.doi.org/10.1504/IJBNN.2010.034654]
[25]
Gasco MR. Method of producing solid lipid microspheres having narrow size distribution. US Patent No. 5250236, 1993.
[26]
Gasco MR. Solid lipid nanospheres from warm micro emulsions. Pharm Technol Eur 1997; 9: 52-8.
[27]
Sanad RA, AbdelMalak NS, elBayoomy TS, Badawi AA. Formulation of a novel oxybenzone-loaded nanostructured lipid carriers (NLCs). AAPS PharmSciTech 2010; 11(4): 1684-94.
[http://dx.doi.org/10.1208/s12249-010-9553-2] [PMID: 21107771]
[28]
Seyfoddin A, Al-Kassas R. Development of solid lipid nanoparticles and nanostructured lipid carriers for improving ocular delivery of acyclovir. Drug Dev Ind Pharm 2013; 39(4): 508-19.
[http://dx.doi.org/10.3109/03639045.2012.665460] [PMID: 22424312]
[29]
Patel D, Dasgupta S, Dey S, Ramani YR, Ray S, Mazumder B. Nanostructured lipid carriers (NLC)-based gel for the topical delivery of aceclofenac: Preparation, characterization, and in vivo evaluation. Sci Pharm 2012; 80(3): 749-64.
[http://dx.doi.org/10.3797/scipharm.1202-12] [PMID: 23008819]
[30]
Iftime MM, Dobreci DL, Irimiciuc SA, Agop M, Petrescu T, Doroftei B. A theoretical mathematical model for assessing diclofenac release from chitosan-based formulations. Drug Deliv 2020; 27(1): 1125-33.
[http://dx.doi.org/10.1080/10717544.2020.1797242] [PMID: 32720542]
[31]
Pena LE, Osborne DW, Amann AH. Topical drug delivery formulation. Marcel Dekker 1990; pp. 381-8.
[32]
Phillips CR, Brasington RD. Osteoarthritis treatment update: Are NSAIDs still in the picture. J Musculoskelet Med 2010; 27(2) Available from: rheumatologynetwork.com/view/osteoarthritis-treatment-update-are-nsaids-still-picture
[33]
Rastogi V, Yadav P. Transdermal drug delivery system: An overview. Asian J Pharm 2012; 6(3): 161-70.
[http://dx.doi.org/10.4103/0973-8398.104828]
[34]
Sharma A, Saini S, Rana A. Transdermal drug delivery system: A review. Int J Res Pharm Biomed Sci 2013; 4: 286-92.
[35]
Tortora GJ, Grabowski SR. Principle of Anatomy and physiology. (10th ed.), Hoboken: John Wiley & Sons 2002.
[36]
Waugh A, Grant A. Ross and Wilson Anatomy and Physiology in health and illness. (10th ed.), Churchill Livingstone 2006.
[37]
Langer R. Transdermal drug delivery: past progress, current status, and future prospects. Adv Drug Deliv Rev 2004; 56(5): 557-8.
[http://dx.doi.org/10.1016/j.addr.2003.10.021] [PMID: 15019745]
[38]
Abdallah MH. Transfersomes as a transdermal drug delivery system for enhancement the antifungal activity of nystatin. Int J Pharm Pharm Sci 2013; 5(4): 560-7.
[39]
Guinedi AS, Mortada ND, Mansour S, Hathout RM. Preparation and evaluation of reverse-phase evaporation and multilamellar niosomes as ophthalmic carriers of acetazolamide. Int J Pharm 2005; 306(1-2): 71-82.
[http://dx.doi.org/10.1016/j.ijpharm.2005.09.023] [PMID: 16263229]
[40]
Zhang ZH, Zhang YL, Zhou JP, Lv HX. Solid lipid nanoparticles modified with stearic acid-octaarginine for oral administration of insulin. Int J Nanomedicine 2012; 7: 3333-9.
[PMID: 22848162]
[41]
Tirumalesh C, Suram D, Dudhipala N, Banala N. Enhanced pharmacokinetic activity of Zotepine via nanostructured lipid carrier system in Wistar rats for oral application. Pharm Nanotechnol 2020; 8(2): 148-60.
[http://dx.doi.org/10.2174/2211738508666200225113359] [PMID: 32096755]
[42]
Kaur N, Sharma K, Bedi N. Topical nanostructured lipid carrier based hydrogel of mometasonefuroate for the treatment of psoriasis. Pharm Nanotechnol 2018; 6(2): 133-43.
[http://dx.doi.org/10.2174/2211738506666180523112513] [PMID: 29788899]
[43]
Ranpise HA, Gujar KN, Pawar SC, et al. Formulation, optimization, and evaluation of ketoconazole loaded nanostructured lipid carrier gel for topical delivery. Drug Deliv Lett 2020; 10(1): 61-71.
[http://dx.doi.org/10.2174/2210303109666190717155731]
[44]
Agarwal S. HariKumar SL, Negi P, Upadhyay N, Garg R. Quetiapine fumarate loaded nanostructured lipid carrier for enhancing oral bioavailability: design, development and pharmacokinetic assessment. Curr Drug Deliv 2021; 18(2): 184-98.
[http://dx.doi.org/10.2174/18755704MTA48NTcpw] [PMID: 32723273]
[45]
Gade S, Patel KK, Gupta C, et al. An ex vivo evaluation of moxifloxacin nanostructured lipid carrier enriched in situ gel for transcorneal permeation on goat cornea. J Pharm Sci 2019; 108(9): 2905-16.
[http://dx.doi.org/10.1016/j.xphs.2019.04.005] [PMID: 30978345]
[46]
Ranpise HA, Gujar KN, Mathure D, et al. Skin targeting of oxiconazole nitrate loaded nanostructured lipid- carrier gel for fungal infections. Pharm Nanotechnol 2018; 6(3): 192-200.
[http://dx.doi.org/10.2174/2211738506666180913125918] [PMID: 30210010]
[47]
Wairkar S, Patel D, Singh A. Nanostructured lipid carrier based dermal gel of cyclosporine for atopic dermatitis-in vitro and in vivo evaluation. J Drug Deliv Sci Technol 2022; 72: 103365.
[http://dx.doi.org/10.1016/j.jddst.2022.103365]
[48]
Patlolla RR, Chougule M, Patel AR, Jackson T, Tata PNV, Singh M. Formulation, characterization and pulmonary deposition of nebulized celecoxib encapsulated nanostructured lipid carriers. J Control Release 2010; 144(2): 233-41.
[http://dx.doi.org/10.1016/j.jconrel.2010.02.006] [PMID: 20153385]
[49]
Jain K, Sood S, Gowthamarajan K. Optimization of artemether-loaded NLC for intranasal delivery using central composite design. Drug Deliv 2015; 22(7): 940-54.
[http://dx.doi.org/10.3109/10717544.2014.885999] [PMID: 24512368]
[50]
Patwekar SL, Pedewad SR, Gattani S. Development and evaluation of nanostructured lipid carriers-based gel of isotretinoin. Particul Sci Technol 2018; 36(7): 832-43.
[http://dx.doi.org/10.1080/02726351.2017.1305026]
[51]
Sharma S, Sathasivam T, Rawat P, Pushpamalar J. Lycopene-loaded nanostructured lipid carrier from carboxymethyl oil palm empty fruit bunch cellulose for topical administration. Carbohydr Polymer Technol Appl 2021; 2: 100049.
[52]
Cunha S, Costa CP, Loureiro JA, et al. Double optimization of rivastigmine-loaded Nanostructured Lipid Carriers (NLC) for nose-to-brain delivery using the Quality by Design (QbD) approach: Formulation variables and instrumental parameters. Pharmaceutics 2020; 12(7): 599.
[PMID: 32605177]
[53]
Kumarm N, Gupta GD, Arora D. DoE directed optimization, development and characterization of resveratrol loaded nlc system for the nose to brain delivery in the management of glioblastoma multiforme. Drug Develop Indust Pharm 2020; 46: 227-35.
[54]
Velmurugan R, Selvamuthukumar S. Development and optimization of ifosfamide nanostructured lipid carriers for oral delivery using response surface methodology. Appl Nanosci 2016; 6(2): 159-73.
[http://dx.doi.org/10.1007/s13204-015-0434-6]
[55]
Brito Raj S, Chandrasekhar KB, Reddy KB. Formulation, in vitro and in vivo pharmacokinetic evaluation of simvastatin nanostructured lipid carrier loaded transdermal drug delivery system. Fut J Pharm Sci 2019; 5(1): 9.
[http://dx.doi.org/10.1186/s43094-019-0008-7]
[56]
Patel RJ, Patel ZP. Formulation optimization and evaluation of nanostructured lipid carriers containing valsartan. Inter J Pharm Sci Nanotechnol 2013; 6(2): 2077-86.
[http://dx.doi.org/10.37285/ijpsn.2013.6.2.10]
[57]
Han F, Yin R, Che X, et al. Nanostructured lipid carriers (NLC) based topical gel of flurbiprofen: Design, characterization and in vivo evaluation. Int J Pharm 2012; 439(1-2): 349-57.
[http://dx.doi.org/10.1016/j.ijpharm.2012.08.040] [PMID: 22989987]
[58]
Uprit S, Kumar Sahu R, Roy A, Pare A. Preparation and characterization of minoxidil loaded nanostructured lipid carrier gel for effective treatment of alopecia. Saudi Pharm J 2013; 21(4): 379-85.
[http://dx.doi.org/10.1016/j.jsps.2012.11.005] [PMID: 24227958]
[59]
Mendes IT, Ruela ALM, Carvalho FC, Freitas JTJ, Bonfilio R, Pereira GR. Development and characterization of nanostructured lipid carrier-based gels for the transdermal delivery of donepezil. Colloids Surf B Biointerfaces 2019; 177: 274-81.
[http://dx.doi.org/10.1016/j.colsurfb.2019.02.007] [PMID: 30763792]
[60]
Sachan AK, Gupta A, Arora M. Formulation & characterization of nanostructured lipid carrier (NLC) based gel for topical delivery of etoricoxib. J Drug Deliv Ther 2016; 6(2): 4-13.
[http://dx.doi.org/10.22270/jddt.v6i2.1222]
[61]
Gaba B, Fazil M, Khan S, Ali A, Baboota S, Ali J. Nanostructured lipid carrier system for topical delivery of terbinafine hydrochloride. Bull Fac Pharm Cairo Univ 2015; 53(2): 147-59.
[http://dx.doi.org/10.1016/j.bfopcu.2015.10.001]
[62]
Motawea A, Borg T, Abd El-Gawad AEGH. Topical phenytoin nanostructured lipid carriers: Design and development. Drug Dev Ind Pharm 2018; 44(1): 144-57.
[http://dx.doi.org/10.1080/03639045.2017.1386204] [PMID: 28956451]
[63]
Otarola JJ, Cobo Solis AK, Farias ME, Garrido M, Mariano Correa N, Molina PG. Piroxicam-loaded nanostructured lipid carriers gel: Design and characterization by square wave voltammetry. Colloids Surf A Physicochem Eng Asp 2020; 606: 125396.
[http://dx.doi.org/10.1016/j.colsurfa.2020.125396]
[64]
Mahant S, Rao R, Souto EB, Nanda S. Analytical tools and evaluation strategies for nanostructured lipid carrier-based topical delivery systems. Expert Opin Drug Deliv 2020; 17(7): 963-92.
[http://dx.doi.org/10.1080/17425247.2020.1772750] [PMID: 32441158]
[65]
Gujjar S, Madhavi BLR, Karki R. Formulation and evaluation of topical gel containing nanostructured lipid carriers dispersion of an antifungal drug. ACTA Pharmaceutica Sciencia 2019; 57(4): 57-75.
[http://dx.doi.org/10.23893/1307-2080.APS.05724]
[66]
Yuan H, Wang LL, Du YZ, You J, Hu FQ, Zeng S. Preparation and characteristics of nanostructured lipid carriers for control-releasing progesterone by melt-emulsification. Colloids Surf B Biointerfaces 2007; 60(2): 174-9.
[http://dx.doi.org/10.1016/j.colsurfb.2007.06.011] [PMID: 17656075]

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