Sitem ŞAHİN, Gülengül DUMAN, Ece GENÇ, Alper YAMAN, Elif Çiğdem ALTUNOK

Application of Tramadol Hydrogel as a Transdermal Drug Delivery with Sonophoresis Device to Rats

Transdermal drug delivery offers an appealing alternative to injections and oral medications. However, applications of transdermal drug delivery are constrained to only a few drugs due to low skin permeability. Application of low‐frequency ultrasound enhances skin permeability, a phenomenon called as low‐frequency sonophoresis. The skin consists of two important layers called epidermis and dermis, which are on the fatty layer called hypodermis (subcutaneous tissue). The epidermis is the outermost layer of the skin. It consists mainly of cells called “keratinocytes”. This is caused by the evolution of cells formed in the lower layer and their accumulation on top of each other. At the top is the stratum corneum epidermidis layer from almost completely dead cells. Stratum corneum acts as a primary barrier to drug delivery, transdermal drug delivery technique precedes to conventional drug delivery process. In this study, tramadol hydrogel is an opioid-like analgesic with much less adverse impact was carried out to rat skin. The tramadol hydrogel was applied on rat skin by using a novel developed sonophoretic device. There were 4 groups of Sprague Dawley male rats that were examined to evaluate analgesia. The first group was control group, the second was intraperitoneal (i.p.) application group, the third was tramadol hydrogel without sonophoresis application and the last group was tramadol hydrogel with sonophoresis application. It was shown that tramadol used with sonophoresis increased analgesic effect three-fold than tramadol hydrogel group 30 minutes later. Hotplate analgesia meter was used and the efficacy was measured on 16 rats. Tramadol dosage was 28 mg per kilogram for each rat. Low frequency sonophoresis device transducer was adjusted to 40 kilohertz (kHz) frequency for up to 60 minutes. Measurements were carried out at 0, 10, 20, 30, 40 and 60 minutes. There was a statistically significant difference between tramadol hydrogel and tramadol hydrogel with sonophoresis groups (p<0.05, by Kruskal Wallis test). Moreover, the developed sonophoretic device application was successful and application low frequency 40 kHz was safe. Neither burn nor erythematous streaks were observed on rat skin by using low frequency sonophoresis. The administration of tramadol hydrogel and tramadol hydrogel with sonophoresis groups were examined, the absorption of tramadol increased by 2-3 times transdermally.

Keywords:

Tramadol hydrogel hot plate analgesia test, sonophoresis device, transdermal drug delivery, Spraque Dawley rats, low frequency,

PDF

___

Ankier, S. I. (1974). New hot plate tests to quantify antinociceptive and narcotic antagonist activities. European journal of pharmacology, 27(1), 1-4.
Bamigbade, T. A., Langford, R. M. (1998). The clinical use of tramadol hydrochloride. Pain Reviews, 5, 155-182.
Bartek, M. J., Labudde, J. A. and Maibach, H. I. (1972). Skin permeability in vivo: comparison in rat, rabbit, pig and man. Journal of Investigative Dermatology, 58(3), 114-123. https://doi.org/10.1111/1523-1747.ep12538909
Bird, R. B., Stewart, W. E., Lightfoot, E. N. (1960). Transport phenomena, 11, 5.
Bommannan, D., Menon, G. K., Okuyama, H., Elias, P. M., Guy, R. H. (1992). Sonophoresis. II. Examination of the mechanism(s) of ultrasound-enhanced transdermal drug delivery. Pharmaceutical Research, 9(8),1043-1047.
Bouhadir, K. H., Lee, K. Y., Alsberg, E., Damm, K. L., Anderson, K. W., Mooney, D. J. (2001). Degradation of partially oxidized alginate and its potential application for tissue engineering. Biotechnology Progress, 17(5), 945-950. https://doi.org/10.1021/bp010070p
Chaturvedi, M., Kumar, M. and Pathak, K. (2011). A review on mucoadhesive polymer used in nasal drug delivery system. Journal of Advanced Pharmaceutical Technology & Research, 2(4), 215. Doi: 10.4103/2231-4040.90876
Fernyhough, J. C.,Schmandle J. J., Weigel, M. C., Edwards, C. C., Levine A. M. et al. (1992). Chronic donor site pain complicating bone graft harvesting from the posterior iliac crest for spinal fusion. Spine, 17(12), 1474-1480. Doi: 10.1097/00007632-199212000-00006
Guvendiren, M., Lu, H. D. and Burdick, J. A. (2012). Shear-thinning hydrogels for biomedical applications. Soft Matter, 8(2), 260-272. Doi: 10.1039/C1SM06513K
Guy, R. H. (Ed.) and Hadgraft J. (Ed.) (2003).Transdermal drug delivery. 2nd Ed., Marcel Dekker, New York, US, Basel, CH.
Hama, A., Sagen, J. (2007). Altered antinociceptive efficacy of tramadol over time in rats with painful peripheral neuropathy. European Journal of Pharmacology, 559(1), 32-37. https://doi.org/10.1016/j.ejphar.2006.11.047
Hussain, T., Ranjha, N. M., Shahzad, Y. (2011). Swelling and controlled release of tramadol hydrochloride from a pH-sensitive hydrogel. Designed Monomers and Polymers, 14(3), 233-249. https://doi.org/10.1163/138577211X557521
Husseini, G. A., Rosa, M. A. D., Richardson, E. S., Christensen, D. A., Pitt, W. G. (2005). The role of cavitation in acoustically activated drug delivery. Journal of Controlled Release, 107(2), 253-261. https://doi.org/10.1016/j.jconrel.2005.06.015