PREPARATION AND EVALUATION OF FENTANYL TRANSDREMAL PATCHES USING LIDOCAINE AS A MODEL DRUG AND AZELAIC ACID AS A PENETRATION ENHANCER

Authors

  • Nawal A. Rajab Department of pharmaceutics, collage of pharmacy, university of Baghdad
  • Alaa A. Abdul Rassol Department of pharmaceutics, collage of pharmacy, university of Baghdad.
  • Shereen M. Assaf Department of pharmaceutics, collage of pharmacy, university of Baghdad.
  • Al-sayed A. Sallam Department of pharmaceutics, collage of pharmacy, university of Baghdad.

Keywords:

Azelaic acid, Permeation enhancer, Fentanyl and Transdermal patches

Abstract

Transdermal drug delivery offers numerous advantages over the conventional routs of administration; however, poor permeation of most drug across the skin barrier constitutes a major limitation of this rout.

Objective: The possibility of utilizing azelaic acid as penetration enhancer was investigated. And then development of a new transdermal controlled-release device using of non-medicated and lidocaine transdermal patches and then testing the feasibility of loading fentanyl patch.

Methods: DSC, FTIR, X-ray diffraction analysis and skin permeability measurements were done for both skin sample untreated and treated with azelaic acid to prove the possibility of utilizing it as permeation enhancer.

Multilayered lidocaine transdermal patches were prepared by solvent/evaporation casting technique using Eudragit® E100 as transdermal adhesive polymer, and ethyl vinyl acetate as impermeable backing layer. The flexibility of films required for a good compliance and optimum transdermal adhesion of the Eudragit E films was achieved by employing triethyl citrate or dibutylphthalate at concentration of 25% (w/w) of polymer. A physicochemical interaction between azelaic acid and Eudragit E100 (cationic polymer) has been evaluated using FTIR and DSC. Lidocaine as well as fentanyl bilayerd transdermal patches containing triethylcitrate at concentration of 25% (w/w) of Eudragit E100 with and without azelaic acid were selected for further permeation studies

Results: The obtained results indicated that fluorescien permeation through epidermal human skin treated with overnight exposure to saturated aqueous solution of azelaic acid was increased by 8.6 folds while, its permeation through rat skin was increased by 10.89 folds. Additional analysis by FTIR, X-ray diffraction, SEM, and DSC showed that azelaic acid disrupted stratum corneum lipid, which supported its action as promising penetration enhancer.Plasticizers as triethyl citrate or dibutylphthalate at concentration of 25% (w/w) of polymer reduced Tg of Eudragit E100 polymer to about 15.50C and 26.20C respectively. A physicochemical interaction between azelaic acid and Eudragit E100 was proven by FTIR study which indicated the present of ionic bonding between them, while DSC showed that azelaic acid may act as non-traditional plasticizer through its reduction in Tg by 7.30 C.The results of permeation studies indicated that the presence of azelaic acid was significantly increased (P < 0.05) the drug flux as the concentration of azelaic acid increased. As well as; fentanyl transdermal permeability studies revealed similar behavior to lidocaine as drug flux increased by 4.82 folds at AZ concentration of 2mg/cm2.

Conclusion: the overall obtained data revealed the feasibility of preparing a controlled release fentanyl transdermal patches containing azelaic acid as penetration enhancer.

Downloads

Download data is not yet available.

References

Sonia Dhiman, Thakor G S, Ashish K R, Transdermal patches:arecent approach to new drug delivery system. Int J of Pharmacy and Pharm Sci 2011;3 (5):0975-1491.

Martindale. the Extra pharmacopoeia,.33ed 2002:1110.

Arun Raj R, Formulation evaluation and in vitro permeation studies of transdermal nifedipine from matrix type patches. Int J of Pharmacy and Pharm Sci 2014;6 (1):0975-1491.

Mohammad Wais, Abudus Samad, Iram Nazish, Anubha Khale, Mohd Agil, Mohib Khan, Formulation development ex-vivo and in-vivo evaluation of nanoemulsion for transdermal delivery of glibenclamide. Int J of Pharmacy and Pharm Sci 2013;5 (4):0975-1491.

Peter N, Bennett, Marris J. Brown, Clinical Pharmacology, 10thed. J Churchill Livingstone 2008:274.

Kligman AM, Christophers E. Preparation of isolated sheets of human sratum corneum. J Arch Dermatol 1963;88:702-5.

Wagner Ky, Cho J, Choi HK. Enhancement of percutaneous absorption of ketoprofen:effect of vehicles and adhesive matrix. Int J Pharm 1998;169:95-104.

Yui N, Okuhara M, Okano M, and Sakurai Y. Change in water structure in the stratum corneum of hairless rat skin by subcutaneous enhancers and its effect on indomethacin permeation. J Drug Deliv Syst 1992;7:1199-203.

Bhatia KS, Gao S, and Singh J. Effect of penetration enhancers and iontophoresis on FT-IR spectroscopy and LHRH permeability through porcine skin. J Control Rel 1997;47:81-9.

Krishnaiah YSR, Satyanarayana V, and Karthikeyan RS. Effect of the solvents system on the in vitro permeation of nicardipine hydrochloride through exised rat epidermis. J Pharm Pharmaceut 2002;5(2):124-30.

Goodman M, Barry BW. Differential scanning calorimetry of human stratum corneum:effects of penetration enhancers Azone and dimethyl sulphoxide. J Anal Proc 1986;23:397-8.

Lopez O, Cocera M, Campos L, de la Maza A, Coderch L, Parra JL. Use of wide and small angle X-ray diffraction to study the modifications in the stratum corneum induced by octyl glucoside. J Physicochem Eng Asp 200;162:123-30.

Kitagawa S, Sawada M, Hirata H. Fluorescence analysis with diphenylhexatriene and its ionic derivatives of the fluidity of liposomes constituted from stratum-corneum lipids-contribution of each lipid component and effects of long-chain unsaturated fatty-acids. Int J Pharm 1993;98:203-8.

Chun Y, Peter J. Ludovice, Mark R. Transdermal delivery enhanced by maganin pore-forming peptide. J Control Rel 2007;122(3):375-83.

Arora P, Mukherjee B. Design, development, physicochemical and in vitro and in vivo evaluation of transdermal patches containing diclofenac diethylammonium salt. J Pharm Sci 2002;91:2076-89.

Abu-Huwaiji R. Development and in vitro/ in vivo testing of mucoadhesive buccal patches releasing fentanyl citrate. Ph.D. Thesis, Faculty of Pharmacy-Jordan University of Science and Technology (2004).

Gristina P, Gaia C, Sara N, et al. Bioadhesive film for the transdermal delivery of lidocaine:in vitro and in vivo behavior. J Control Rel 2003;88:277-85.

Al-Akayleh F. Investigation of drug-excipient interaction phenomena in relation to enhancement of transdermal drug delivery. Ph.D. Thesis, Faculty of Pharmacy-University of Baghdad (2004).

Claudia L-Salva, Pereira J, Ramalho A, et al. Films based on chitosan polyelectrolyte complexes for skin drug delivery:development and characterization. J Memb Sci 2008;320:268-79.

Laboratory 3:Thermal transitions in polymeric materials. Polymer Characterization Lab. J Spring 00-3.

British Pharmacopeias, 2007.

Roy SD, Gutierrez M, Flynn GL, Gary WC. Controlled transdermal delivery of fentanyl:characterization of pressure-sensitive adhesive for matrix patch design. J Pharm Sci 1996;85(5):491-5.

Claudia S, Lippold BC. An attempt to clarify the mechanism of the penetration enhancing effect of lipophilic vehicle with differential scanning calorimetry (DSC). J Pharm Pharmcol 1995;47:276-81.

Takeuchi Y, Yasukawa H, Yamaoka Y, et al. Effects of fatty-acids, fatty amines and propylene-glycol on rat stratum-corneum lipids and proteins in vitro measured by Fourier-transform infrared attenuated total reflection (FT-IR/ATR) spectroscopy. J Chem Pharm Bull 1992;40:1887-92.

Potts RO, Golden GM, Francoeur ML, et al. Mechanism and enhancement of solute transport across the stratum-corneum. J Control Rel 1991;15:249-60.

Yeagle PL. Cholesterol and the cell-membrane. J Biochim Biophys Acta 1985;822:267-87.

Pappinen S, Hermansson M, Kuntsche J, et al. Comparison of rat epidermal keratinocyte organotypic culture (ROC) with intact human skin:lipid composition and thermal phase behaviour of stratum corneum. J Biochim Biophys Acta-Biomembranes 2008;1778:824-34.

Rohm Pharm Information Sheets. Rohm Pharm GmbH, Weiterstadt;info. J EudragitE 100.

Barry WB. Novel mechanisms and devices to enable successful transdermal delivery system. Eur J Pharm 2001;14:101-14.

Yamashita F, Koyama Y, Kitano M, Hashida. Analysis of in vivo skin penetration enhancement by oleic acid based on two-layer diffusion model with polar and nonpolar routes in the stratum corneum. Int J Pharm 1995;117:173-9.

Published

01-07-2014

How to Cite

Rajab, N. A., A. A. A. Rassol, S. M. Assaf, and A.- sayed A. Sallam. “PREPARATION AND EVALUATION OF FENTANYL TRANSDREMAL PATCHES USING LIDOCAINE AS A MODEL DRUG AND AZELAIC ACID AS A PENETRATION ENHANCER”. International Journal of Pharmacy and Pharmaceutical Sciences, vol. 6, no. 7, July 2014, pp. 615-20, https://www.innovareacademics.in/journals/index.php/ijpps/article/view/1999.

Issue

Section

Original Article(s)