ENHANCED TRANSDERMAL PERMEABILITY OF DICLOFENAC DIETHYLAMINE USING NANOEMULSION VEHICLE
Abstract
The transdermal delivery of Diclofenac diethylamine has attracted considerable interest in recent years due to a lot of significant properties. Transdermal delivery system exhibits very poor permeation through the skin. Thus, an attempt was made to enhance the transdermal permeability of drug using nanoemulsion as vehicle. The main objective of this study was to develop a potential of nanoemulsion formulation for transdermal delivery of Diclofenac diethylamine for inflammatory disease. Transdermal patches were prepared using solvent evaporation technique. In this investigation, the transdermal patches (control) and nanoemulsion containing transdermal patches were prepared, compared and characterized for different physicochemical parameters (moisture content, moisture uptake folding endurance, in-vitro drug release). The optimized batch was also subjected for in-vivo anti-inflammatory study, pharmacokinetics (Cmax, Tmax and AUC) study and skin irritation study. The physical evaluation indicated that the prepared batches were smooth, flexible and translucent. The transdermal patch having 1:5 ratio of polyvinyl pyrrolidone and ethyl cellulose, exhibited a 1.7 fold increase in skin permeation compare to Diclofenac diethylamine patch. Nanoemulsion containing transdermal patch showed a significant increase in permeation parameters such as steady state flux (Jss); 0.061 mgcm-2hr-1 and permeability coefficient (Kp); 0.025 cmhr-1, when compared to the control. The mean Cmax of drug for optimized transdermal patch (TD) and nanoemulsion transdermal patch (NETD) was 2.56µg/ml and 3.42µg/ml, respectively. The in-vivo studies revealed a constant plasma concentration of drug for long period. Thus, results indicated that the nanoemulsion containing transdermal patches can be a promising tool for enhancing the percutaneous delivery of Diclofenac diethylamine.
Keywords:
Nanoemulsion, Transdermal, Diclofenac diethylamine, In-vivo, PharmacokineticReferences
2. Monkhouse DC, Huq AS. Transdermal drug delivery–problems and Promises. Drug Dev. Ind. Pharm. 1988; 14: 183-203.
3. Brown MB, Martin GP, Jones SA, Akomeah FK. Dermal and transdermal drug delivery systems current and future prospects. Drug Del. 2006; 13: 175-187.
4. Kong M, Chen XG, Kweon Dk, Park HJ. Investigation on skin permeation of Hyaluronic acid based nanoemulsion as transdermal carrier. Carbohydrate Polymers. 2011; 86: 837-843.
5. Küchler S, Radowski MR, Blaschke T, Dathe M, Plendl J, Haag R. Nanoparticles for skin penetration enhancement – A comparison of adendritic core - multi shell-nano transporter and solid lipid nanoparticles. Eur. J. Pharm. Biopharm. 2009; 71: 243–250.
6. Kong M, Park HJ. Stability investigation of hyaluronic acid based nanoemulsion and its potential as transdermal carrier. Carbohydr. Polym. 2011; 83: 1303-1310.
7. Kogan A, Garti N. Microemulsions as transdermal drug delivery vehicles. Adv. Colloid. Interface. Sci. 2006; 123: 369-385.
8. Elena P, Paola S, Maria RG. Transdermal permeation of apomorphine through hairless mouse skin from microemulsions. Int. J. Pharm. 2001; 226: 47-51.
9. Gan TJ. Diclofenac: an update on its mechanism of action and safety profile. Curr. Med. Res. Opin. 2010; 26: 1715-1731.
10. Niethard FU, Gold MS, Solomon GS, Liu JM, Unkauf M, Albrecht HH, Elkik F. Efficacy of topical Diclofenac Diethylamine gel in osteoarthritis of the knee. J. Rheumatol. 2005; 32: 2384-2392.
11. Kulkarni RV, Wagh YJ, Setty CM, Sa B. Development and characterization of sodium alginate-hydroxypropyl methylcellulose polyester multilayered hydrogel membranes for drug delivery through skin. Polym. Plast. Technol. Eng. 2011; 50: 490-497.
12. Minghetti P, Cilurzo F, Casiraghi A, Montanari L, Fini A. Ex vivo study of transdermal permeation of four diclofenac salts from different vehicles. J. Pharm. Sci. 2007; 96: 814-823.
13. Arora P, Mukherjee B. Design, development, physicochemical, and In vitro and In vivo evaluation of transdermal patches containing diclofenac diethyl ammonium salt. J. Pharm. Sci. 2002; 91: 2089-2096.
14. Amnuaikit C, Ikeuchi I, Ogawara K, Higaki K, Kimura T. Skin permeation of propranolol from polymeric film containing terpene enhancers for transdermal use. Int. J. Pharm. 2005; 289: 167-178.
15. Ubaidulla U, Reddy MVS, Ruckmani K, Ahmed FJ, Khar RK. Transdermal therapeutics system of carvedilol: Effect of hydrophilic and hydrophobic matrix on in vitro and in vivo characteristics, AAPS Pharm. Sci. Tech. 2007; 8: E13–E20.
16. Baichwal RW. Advances in drug delivery systems, MSR Foundation: Bombay. 1983:136-147.
17. Sadhana P, Gupta SP, Jain SK. Effective and controlled transdermal delivery of metoprolol tartarate. Indian J. Pharm. Sci. 2005; 67: 346-350.
18. Nashwa A, El-Gendy, Nirmeen A, Sabry, Mai EA, Emad O, Manal M. Transdermal patch incorporating salbutamol sulphate: In vitro and clinical characterization. Drug Discov. Ther. 2008; 2: 200-210.
19. Panchaxari DM, Pampana S, Pal T, Devabhaktuni B, Aravapalli AK. Design and characterization of diclofenac diethylamine transdermal patch using silicone and acrylic adhesives combination. DARU J. Pharm. Sci. 2013; 21: 1-14.
20. Johnson ME, Blankschtein D, Langer R. Evaluation of solute permeation through the stratum corneum: Lateral bilayer diffusion as the primary transport mechanism. J. Pharm. Sci. 1997; 86: 1162-1172.
21. Winter CA. Anti-inflammatory testing methods: comparative evaluation of indomethacin and other agents. In: Garattini S, Dukes MNG, eds. International Symposium on Nonsteroidal Anti-inflammatory Drugs, Amsterdem, Excerpta Medica Foundation. 1964:190–202.
22. Draize J, Woodard G, Calvery H. Methods for the study of irritation and toxicity of substances applied topically to the skin and mucous membranes. J. Pharmacol. Exp. Ther. 1944; 82: 377-390.
23. Sevastre AS, Popescu F, Berbecaru A, Croitoru O, Baniceru M. Pharmacokinetic evaluation after percutaneous administration of some non steroidal anti inflamatory drug preparations using animal experiments. Ther. Pharmacol. Clin Toxicol. 2009; XIII: 161-166.
Published
Abstract Display: 313 
PDF Downloads: 351 
