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Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry

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ISSN (Print): 1871-5230
ISSN (Online): 1875-614X

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Research Article

Development of Betamethasone Dipropionate-Loaded Nanostructured Lipid Carriers for Topical and Transdermal Delivery

Author(s): Pierre A. Hanna, Mamdouh M. Ghorab* and Shadeed Gad

Volume 18, Issue 1, 2019

Page: [26 - 44] Pages: 19

DOI: 10.2174/1871523017666181115104159

Abstract

Introduction: Betamethasone dipropionate is a highly effective corticosteroid anti-inflammatory. However, the main drawback of its topical use is the limited skin penetration into deeper skin layers. Also, its systemic use has shown many side effects.

Objective: The goal of this research was to formulate betamethasone dipropionate in nanostructured lipid carriers (NLC) formulae that contain oleic acid to aid its penetration to deeper skin layers and to aid absorption to local regions upon topical application.

Methods: NLC formulae were prepared by high shear homogenization then sonication. Formulae were characterized for their particle size, size distribution, electric potential, occlusion factor, entrapment efficiency, drug loading, transmission electron microscopy, in vitro drug release, and ex vivo skin penetration. Compatibility of ingredients with drug was tested using differential scanning calorimetry. Formulae were shown to have appropriate characteristics. NLC formulae were superior to traditional topical formulation in drug release.

Results: Upon testing ex vivo skin penetration, betamethasone dipropionate prepared in NLC formulae was shown to penetrate more efficiently into skin layers than when formulated as a traditional cream. NLC formulation that contained higher percentage of oleic acid showed higher penetration and higher amount of drug to pass through skin.

Conclusion: In general, NLC with lower oleic acid percentage was shown to deliver betamethasone dipropionate more efficiently into deeper skin layers while that of a higher oleic acid percentage was shown to deliver the drug more efficiently into deeper skin layers and through the skin, transdermally.

Keywords: Absorption, betamethasone dipropionate, NLC, oleic acid, skin penetration, transdermal.

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[1]
Fouad, S.A.; Basalious, E.B.; El-Nabarawi, M.A.; Tayel, S.A. Microemulsion and poloxamer microemulsion-based gel for sustained transdermal delivery of diclofenac epolamine using in-skin drug depot: In vitro/in vivo evaluation. Int. J. Pharm., 2013, 453(2), 569-578.
[2]
Yuan, Y.; Li, S.M.; Yu, L.M.; Deng, P.; Zhong, D.F. Physicochemical properties and evaluation of microemulsion systems for transdermal delivery of meloxicam. Chem. Res. Chin. Univ., 2007, 23(1), 81-86.
[3]
Müller, R.H.; Olbrich, C. Solid lipid nanoparticles: Phagocytic uptake, in vitro cytotoxicity and in vitro biodegradation. Die Pharmbit, 1999, 61(6), 462-467.
[4]
Weyhersn, H.; Ehlers, S.; Hahn, H.; Souto, E.B.; Müller, R.H. Solid Lipid Nanoparticles (SLN)- effects of lipid composition on in vitro degradation and in vivo toxicity. Pharmazie, 2006, 61(6), 539-544.
[5]
Müller, R.H.; Mäder, K.; Gohla, S. Solid Lipid Nanoparticles (SLN) for controlled drug delivery- A review of the state of the art. Eur. J. Pharm. Biopharm., 2000, 50(1), 161-177.
[6]
Radtke, M.; Müller, R.H. Nanostructured lipid carriers (NLC): The new generation of lipid drug carriers. New Drugs, 2001, 2I, 48-52.
[7]
O’Driscoll, C.M. Lipid based formulation for intestinal lymphatic delivery. Eur. J. Pharm. Sci., 2002, 15(5), 405-415.
[8]
Sweetman, S.C. In: Martindale: The Complete Drug Reference; Sweetman, S.C., Ed; 36th ed., Pharmaceutical Press, 2009; pp. 1490-1546.
[9]
Doktorovová, S.; Araújo, J.; Garcia, M.L.; Rakovsky, E.; Souto, E.B. Formulating fluticasone propionate in novel PEG-containing nanostructured lipid carriers (PEG-NLC). Colloids Surf. B Biointerfaces, 2010, 75(2), 538-542.
[10]
Chen, C.C.; Tsai, T.H.; Huang, Z.R.; Fang, J.Y. Effects of lipophilic emulsifiers on the oral administration of lovastatin from nanostructured lipid carriers: Physicochemical characterization and pharmacokinetics. Eur. J. Pharm. Biopharm., 2010, 74(3), 474-482.
[11]
Gonzalez-Mira, E.; Egea, M.A.; Garcia, M.L.; Souto, E.B. Design and ocular tolerance of flurbiprofen loaded ultrasound-engineered NLC. Colloids Surf. B Biointerfaces, 2010, 81(2), 412-421.
[12]
Nayak, A.P.; Tiyaboonchai, W.; Patankar, S.; Madhusudhan, B.; Souto, E.B. Curcuminoids-loaded lipid nanoparticles: Novel approach towards malaria treatment. Colloids Surf. B Biointerfaces, 2010, 81(2), 263-273.
[13]
Park, J.Y.; Lee, K.; Choi, S.A.; Jeong, M.J.; Kim, B.; Lee, J.S.; Oh, Y.K. Sonication-assisted homogenization system for improved lipid extraction from Chlorella vulgaris. Renew. Energy, 2015, 79, 3-8.
[14]
de Vringer, T. Topical preparation containing a suspension of solid lipid particles. European Patent 91200664,, 1992.
[15]
Wissing, S.A.; Lippacher, A.; Müller, R.H. Investigations on the occlusive properties of Solid Lipid Nanoparticles (SLNTM). J. Cosmet. Sci., 2001, 52(2), 313-323.
[16]
Shen, H.; Zhong, M. Preparation and evaluation of Self-Microemulsifying Drug Delivery Systems (SMEDDS) containing atorvastatin. J. Pharm. Pharmacol., 2006, 58(9), 1183-1191.
[17]
Kumbhar, D.D.; Pokharkar, V.B. Engineering of a nanostructured lipid carrier for the poorly water-soluble drug, bicalutamide: Physicochemical investigations. Colloids Surf. A Physicochem. Eng. Asp., 2013, 416, 32-42.
[18]
Higuchi, T.; Connors, K.A. Phase-solubility techniques. Adv. Anal. Chem. Inst, 1965, 4, 117-212.
[19]
Jouyban, A. Handbook of solubility data for pharmaceuticals, 1st ed; CRC Press: Taylor and Francis: Boca Raton, 2010.
[20]
Zou, J.J.; Dai, L.; Ding, L.; Xiao, D.W.; Bin, Z.Y.; Fan, H.W.; Liu, L.; Wang, G.J. Determination of betamethasone and betamethasone 17-monopropionate in human plasma by liquid chromatography- positive/negative electrospray ionization tandem mass spectrometry. J. Chromatogr. B, 2008, 873(2), 159-164.
[21]
Simon, A.; Vinícius Borges, R.A.; Cabral, L.M.; Pereira de Sousa, V. Development and validation of a discriminative dissolution test for betamethasone sodium phosphate and betamethasone dipropionate intramuscular injectable suspension. AAPS PharmSciTech, 2013, 14(1), 425-434.
[22]
Zhang, X.; Liu, J.; Qiao, H.; Liu, H.; Ni, J.; Zhang, W.; Shi, Y. Formulation optimization of dihydroartemisinin nanostructured lipid carrier using response surface methodology. Powder Technol., 2010, 197(1-2), 120-128.
[23]
Larrucea, E.; Arellano, A.; Santoyo, S.; Ygartua, P. Combined effect of oleic acid and propylene glycol on the percutaneous penetration of tenoxicam and its retention in the skin. Eur. J. Pharm. Biopharm., 2001, 52(2), 113-119.
[24]
Silva, L.A.D.; Taveira, S.F.; Lima, E.M.; Marreto, R.N. In vitro skin penetration of clobetasol from lipid nanoparticles: Drug extraction and quantitation in different skin layers. Braz. J. Pharm. Sci., 2012, 48(4), 811-817.
[25]
Vitorino, C.; Almeida, J.; Gonçalves, L.M.; Almeida, A.J.; Sousa, J.J.; Pais, A.A. Co-encapsulating nanostructured lipid carriers for transdermal application: From experimental design to the molecular detail. J. Control. Release, 2013, 167(3), 301-314.
[26]
Patidar, A.; Thakur, D.S.; Kumar, P.; Verma, J. A review on novel lipid based nanocarriers. Int. J. Pharm. Pharm. Sci., 2010, 2(4), 30-35.
[27]
Han, F.; Li, S.; Yin, R.; Liu, H.; Xu, L. Effect of surfactants on the formulation and characterization of a new type of colloidal drug delivery system: Nanostructured lipid carriers. Colloids Surf. A, 2008, 315(1-3), 210-216.
[28]
Malmsten, M. In: Surfactants and Polymers in Drug Delivery; Malmsten M, Ed.; 1st ed, CRC Press: New York, 2002, pp. 164-203.
[29]
Boyadjiev, C. In: Theoretical Chemical Engineering, Modeling and Simulation; Boyadjiev, C. Ed.; 1st ed., Springer Verlag Berlin Heidelberg: New York, 2010; pp. 127-186.
[30]
Wissing, S.A.; Lippacher, A.; Müller, R.H. Investigations on the occlusive properties of Solid Lipid Nanoparticles (SLNTM). J. Cosmet. Sci., 2001, 52, 313-323.
[31]
Mollet, H.; Grubenmann, A. In: Formulation Technology: Emulsions, Suspensions, Solid Form; Mollet, H.; Grubenmann, A.; Ed.; 1st ed., Wiley-VCH Verlag GmbH: Federal Republic of Germany, 2004; pp. 90- 104.
[32]
Puglia, C.; Frasca, G.; Musumeci, T.; Rizza, L.; Puglisi, G.; Bonina, F.; Chiechio, S. Curcumin loaded nlc induces histone hypoacetylation in the CNS after intraperitoneal administration in mice. Eur. J. Pharm. Biopharm., 2012, 81(2), 288-293.
[33]
Swidan, S.A.; Ghonaim, H.M.; Samy, A.M.; Ghorab, M.M. Comparative study of solid lipid nanoparticles and nanostructured lipid carriers for in vitro paclitaxel delivery. J. Chem. Pharm. Res., 2016, 8(5), 482-493.
[34]
Bunjes, H.; Unruh, T. Characterization of lipid nanoparticles by differential scanning calorimetry, X-ray and neutron scattering. Adv. Drug Deliv. Rev., 2007, 59(6), 379-402.
[35]
Motwani, S.K.; Chopra, S.; Talegoankar, S.; Konchan, K.; Ahed, F.J.; Khar, R.K. Chitosan-sodium alginate nanoparticles as submicroscopic reservoirs for ocular delivery: formulation, optimization and in vitro characterization. Eur. J. Pharm. Biopharm., 2008, 68(3), 513-525.
[36]
Gwak, H.S.; Chun, I.K. Effect of vehicles and penetration enhancers on the in vitro percutaneous absorption of tenoxicam through hairless mouse skin. Int. J. Pharm., 2002, 236(1-2), 57-64.

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