Transdermal Delivery of Ondansetron HCl from Thermoreversible Gel Containing Nanocomposite

Author(s): Rabinarayan Parhi* , Surya Santhosh Reddy , Suryakanta Swain .

Journal Name: Current Nanomaterials

Volume 4 , Issue 2 , 2019

Become EABM
Become Reviewer

Graphical Abstract:


Background: Application of thermoreversible gel can be a solution to the low residence time of the topical dosage forms such as normal gel, ointment and cream on the skin surface. Addition of another polymer and a nanocomposite can improve the poor mechanical strength and fast drug release of poloxamer 407 (POL 407) gel. Therefore, it is essential to add xanthan gum (XG) and graphene oxide (GO, thickness 1-2 nm, lateral dimension 1-5 µm) to POL 407 gel to enhance the mechanical strength and to sustain the drug release from the gel.

Methods: Thermal gel of ondansetron hydrochloride (OSH) containing nanocomposite was prepared by adopting cold method. Interaction between drug and polymers was studied using FTIR method, morphological investigation was carried out by optical and scanning electron microscopy method, and rheological study was performed employing rotational rheometer equipped with a cone/plate shear apparatus, gelation temperature by glass bottle method and ex vivo permeation study was performed with cylindrical glass diffusion cell. Skin irritation potential was measured using rat as a model animal.

Results: The FTIR spectrum of the selected gel showed that there is shifting of O-H stretching vibration of a hydroxyl group from 3408.72 to 3360.49 cm-1 and appearance of a new band at 1083.01 cm-1. The spectrum of the selected gel also showed the absence of characteristic peaks of GO at 1625.49 cm- 1. This result indicated that there may be an interaction between OSH and GO and hydrogen bonding between XG and POL 407. The gelation temperature was found to be decreased with the increase in GO content from 14.1±1.21°C 13±0.97°C. SEM micrograph demonstrated the uniform dispersion and intercalation of GO sheets in the gel. All the gel formulations showed a pseudo-plastic flow. Ex vivo permeation study (for 24 hr) exhibited highest (6991.425 µg) and lowest (2133.262 µg) amount of drug release, for OG1 and OG5, respectively. This is attributed to an increase in viscosity which led to a decrease in drug permeation across the abdominal skin of rats. The OG1 formulation (without GO) showed the highest flux of 76.66 µg/cm2/h, permeability coefficient (Kp) of 5.111× 10-3 cm/h and enhancement ratio of 3.277 compared to OG5 containing highest amount (9% w/w) of GO. The selected gel was found to be physically stable and there was minimum irritation score.

Conclusion: All the above results indicated that thermal gel containing nanocomposite sustained the drug release and can be considered as an alternative to the orally administered tablet of OSH.

Keywords: Transdermal delivery, Thermoreversible gel, nanocomposite, graphene oxide, stratum corneum, flux, physical stability.

Rajabalaya R, Tor L-Q, David S. Formulation and in vitro evaluation of ondansetron hydrochloride matrix transdermal systems using ethyl cellulose/polyvinyl pyrrolidone polymer blends. Int Schol Sci Res Innov 2012; 12: 667-71.
Can AS, Erdal MS, Güngör S, Özsoy Y. Optimization and characterization of chitosan films for transdermal delivery of ondansetron. Molecules 2013; 18(5): 5455-71.
Takahashi K, Rytting JH. Novel approach to improve permeation of ondansetron across shed snake skin as a model membrane. J Pharm Pharmacol 2001; 53(6): 789-94.
Teodorescu F, Quéniat G, Foulon C, et al. Transdermal skin patch based on reduced graphene oxide: a new approach for photothermal triggered permeation of ondansetron across porcine skin. J Control Release 2017; 245: 137-46.
Pillai O, Panchagnula R. Transdermal delivery of insulin from poloxamer gel: ex vivo and in vivo skin permeation studies in rat using iontophoresis and chemical enhancers. J Control Release 2003; 89(1): 127-40.
Larrañeta E, Stewart S, Ervine M, Al-Kasasbeh R, Donnelly RF. Hydrogels for hydrophobic drug delivery. classification, synthesis and applications. J Funct Biomater 2018; 9(1): 13.
Peppas NA, Bures P, Leobandung W, Ichikawa H. Hydrogels in pharmaceutical formulations. Eur J Pharm Biopharm 2000; 50(1): 27-46.
Parhi R. Cross-linked hydrogel for pharmaceutical applications: a review. Adv Pharm Bull 2017; 7(4): 515-30.
Kashyap N, Kumar N, Kumar MNVR. Hydrogels for pharmaceutical and biomedical applications. Crit Rev Ther Drug Carrier Syst 2005; 22(2): 107-49.
Maia J, Ribeiro MP, Ventura C, Carvalho RA, Correia IJ, Gil MH. Ocular injectable formulation assessment for oxidized dextran-based hydrogels. Acta Biomater 2009; 5(6): 1948-55.
Escobar-Chávez JJ, López-Cervantes M, Naïk A, et al. Applications of thermo-reversible pluronic F-127 gels in pharmaceutical formulations. J Pharm Pharm Sci 2006; 9(3): 339-58.
Gong CY, Shi S, Dong PW, et al. Biodegradable in situ gel-forming controlled drug delivery system based on thermosensitive PCL-PEG-PCL hydrogel: part 1 synthesis, characterization, and acute toxicity evaluation. J Pharm Sci 2009; 98(12): 4684-94.
Parhi R, Suresh P, Pattnaik S. Transdermal delivery of diltiazem hydrochloride from poloxamer-hpmc gel: in vitro, ex vivo, and in vivo studies. Drug Deliv Lett 2015; 5: 163-72.
Dumortier G, Grossiord JL, Agnely F, Chaumeil JC. A review of poloxamer 407 pharmaceutical and pharmacological characteristics. Pharm Res 2006; 23(12): 2709-28.
Sehgal RR, Roohani-Esfahani SI, Zreiqat H, Banerjee R. Nanostructured gellan and xanthan hydrogel depot integrated within a baghdadite scaffold augments bone regeneration. J Tissue Eng Regen Med 2017; 11(4): 1195-211.
Rhim J-W. Effect of clay contents on mechanical and water vapor barrier properties of agar-based nanocomposite films. Carbohydr Polym 2011; 86: 691-9.
Gilani S, Mir S, Masood M, et al. Triple-component nanocomposite films prepared using a casting method: its potential in drug delivery. J Food Drug Anal 2018; 26(2): 887-902.
Camargo PHC, Satyanarayana KG, Wypych F. Nanocomposites: synthesis, structure, properties and new application opportunities. Mater Res 2009; 12: 1-39.
Anandhan S, Bandyopadhyay S. Polymer nanocomposites: from synthesis to applications Nanocomposites and Polymers with Analytical Methods, InTech Europe, University Campus, STeP Ri. Slavka Krautzeka, Croatia 2011; p. 328.
Jeon I-Y, Baek J-B. Nanocomposites derived from polymers and inorganic nanoparticles. Mater 2010; 3: 3654-74.
Shi Y, Jiang S, Zhou K, et al. Influence of g-C3N4 nanosheets on thermal stability and mechanical properties of biopolymer electrolyte nanocomposite films: a novel investigation. ACS Appl Mater Interfaces 2014; 6(1): 429-37.
Krolow MZ, Hartwig CA, Link GC, et al. Synthesis and characterisation of carbon nanocomposites Carbon Nanostructures. New York: Springer-Verlag Berlin Heidelberg 2013; p. 3347.
Chen S, Wu Q, Mishra C, et al. Thermal conductivity of isotopically modified graphene. Nat Mater 2012; 11(3): 203-7.
Justin R, Chen B. Characterisation and drug release performance of biodegradable chitosan-graphene oxide nanocomposites. Carbohydr Polym 2014; 103: 70-80.
Barahuie F, Saifullah B, Dorniani D, et al. Graphene oxide as a nanocarrier for controlled release and targeted delivery of an anticancer active agent, chlorogenic acid. Mater Sci Eng C 2017; 74: 177-85.
Sovizi MR, Fakhrpour G, Bagheri S, Bardajee GR. Non-isothermal dehydration kinetic study of a new swollen biopolymer silver nanocomposite hydrogel. J Therm Anal Calorim 2015; 121: 1383-91.
Giri A, Ghosh T, Panda AB, Pal S, Bandyopdhyay A. Tailoring carboxymethyl guargum hydrogel with nanosilica for sustained transdermal release of diclofenac sodium. Carbohydr Polym 2012; 87: 1532-8.
Mahdavinia GR, Hosseini R, Darvishi F, Sabzi M. The release of cefazolin from chitosan/polyvinyl alcohol/sepiolite nanocomposite hydrogel films. Iran Polym J 2016; 25: 933-43.
Thakur G, Singh A, Singh I. Formulation and evaluation of transdermal composite films of chitosan-montmorillonite for the delivery of curcumin. Int J Pharm Investig 2016; 6(1): 23-31.
Shaikh S, Birdi A, Qutubuddin S, Lakatosh E, Baskaran H. Controlled release in transdermal pressure sensitive adhesives using organosilicate nanocomposites. Ann Biomed Eng 2007; 35(12): 2130-7.
Biswal T, Samal R, Sahoo PK. Microwave-assisted preparation of poly(2-EHA-co-ST) copolymer and poly(2-EHA-co-ST)/MMT nanocomposite. J Appl Polym Sci 2012; 125: 1467-75.
da Costa Neto BP, da Mata ALML, Lopes MV, Rossi-Bergmann B, Ré MI. Preparation and evaluation of chitosan–hydrophobic silica composite microspheres: Role of hydrophobic silica in modifying their properties. Powder Technol 2014; 255: 109-19.
Gaur PK, Mishra S, Purohit S. Solid lipid nanoparticles of guggul lipid as drug carrier for transdermal drug delivery. BioMed Res Int 2013; 20132013750690
Medhi P, Olatunji O, Nayak A, et al. Lidocaine-loaded fish scale-nanocellulose biopolymer composite microneedles. AAPS PharmSciTech 2017; 18(5): 1488-94.
Schmolka IR. Artificial skin I. Preparation and properties of pluronic F-127 gels for treatment of burns. J Biomed Mater Res 1972; 6(6): 571-82.
Parhi R. Development and optimization of pluronic® F127 and HPMC based thermosensitive gel for the skin delivery of metoprolol succinate. J Drug Deliv Sci Technol 2016; 36: 23-33.
Agrawal V, Gupta V, Ramteke S, Trivedi P. Preparation and evaluation of tubular micelles of pluronic lecithin organogel for transdermal delivery of sumatriptan. AAPS PharmSciTech 2010; 11(4): 1718-25.
Parhi R, Suresh P. Formulation optimization and characterization of transdermal film of simvastatin by response surface methodology. Mater Sci Eng C 2016; 58: 331-41.
Prakash PR, Rao NGR, Soujanya C. Formulation, evaluation and antiinflamatory activity of topical etoricoxib gel. Asian J Pharm Clin Res 2010; 3: 126-9.
Joshi M, Patravale V. Formulation and evaluation of Nanostructured Lipid Carrier (NLC)-based gel of Valdecoxib. Drug Dev Ind Pharm 2006; 32(8): 911-8.
Wang D, Zhao J, Liu X, et al. Parenteral thermo-sensitive organogel for schizophrenia therapy, in vitro and in vivo evaluation. Eur J Pharm Sci 2014; 60: 40-8.
Moghimi HR, Makhmalzadeh BS, Manafi A. Enhancement effect of terpenes on silver sulphadiazine permeation through third-degree burn eschar. Burns 2009; 35(8): 1165-70.
Parhi R, Suresh P, Pattnaik S. Pluronic lecithin organogel (PLO) of diltiazem hydrochloride: effect of solvents/penetration enhancers on ex vivo permeation. Drug Deliv Transl Res 2016; 6(3): 243-53.
Bhatia A, Singh B, Raza K, Wadhwa S, Katare OP. Tamoxifen-loaded lecithin organogel (LO) for topical application: Development, optimization and characterization. Int J Pharm 2013; 444(1-2): 47-59.
Draize JH, Woodard G, Calvery HO. Methods for the study of irritation and toxicity of substances applied topically to the skin and mucous membranes. J Pharmacol Exp Ther 1944; 82: 377-90.
Parhi R, Panchamukhi T. RSM-based design and optimization of transdermal film of ondansetron HCl. J Pharm Innov 2019; 1-6.
Choudhary DR, Patel VA, Chhalotiya UK, Patel HV, Kundawala AJ. Natural polysaccharides as film former: a feasibility study for development of rapid dissolving films of ondansetron hydrochloride. Int J Pharm Pharm Sci 2012; 4(Suppl. 3): 78-85.
Anilkumar A, Murthy TE, Rani AP. Formulation of Ondansetron HCl Matrix Tablets with Microenvironmental pH Modifier for Improved Dissolution and Bioavailability under Hypochlorhydria. Asian J Pharm 2016; 10: 188.
Marcano DC, Kosynkin DV, Berlin JM, et al. Improved synthesis of graphene oxide. ACS Nano 2010; 4(8): 4806-14.
Gurunathan S, Han JW, Kim ES, Park JH, Kim J-H. Reduction of graphene oxide by resveratrol: a novel and simple biological method for the synthesis of an effective anticancer nanotherapeutic molecule. Int J Nanomedicine 2015; 10: 2951-69.
Vintiloiu A, Leroux JC. Organogels and their use in drug delivery--a review. J Control Release 2008; 125(3): 179-92.
Kramaric A, Resman A, Kofler B, Zmitek J. Thermoreversible gel as a liquid pharmaceutical carrier for a galenic formulation. European Patent CA2085690A1 1992.
Yong CS, Choi JS, Quan Q-Z, et al. Effect of sodium chloride on the gelation temperature, gel strength and bioadhesive force of poloxamer gels containing diclofenac sodium. Int J Pharm 2001; 226(1-2): 195-205.
Mukherjee A, Kang JH, Kuznetsov O, et al. Water-soluble graphite nanoplatelets formed by oleum exfoliation of graphite. Chem Mater 2011; 23: 9-13.
Kim S, Sergiienko R, Shibata E, Hayasaka Y, Nakamura T. Production of graphite nanosheets by low-current plasma discharge in liquid ethanol. Mater Trans 2010; 51: 1455-9.
Al-Kassas R, Wen J, Cheng AE-M, Kim AM-J, Liu SSM, Yu J. Transdermal delivery of propranolol hydrochloride through chitosan nanoparticles dispersed in mucoadhesive gel. Carbohydr Polym 2016; 153: 176-86.

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2019
Page: [137 - 147]
Pages: 11
DOI: 10.2174/2405461504666190530123120

Article Metrics

PDF: 5