Journal of Pharmaceutical Investigation

The Korean Society of Pharmaceutical Sciences and Technology (한국약제학회)
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Transdermal Delivery and Analgesic Effects of Lidocaine Hydrogel by Phonophoresis

초음파를 이용한 리도카인 수용성겔의 경피흡수 및 진통효과

  • Published : 2007.06.21
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Abstract

To investigate the permeability of lidocaine, percutaneous absorption studies were performed using excised hairless mouse skin and the penetration of lidocaine via the skin was determined. To increase the skin permeation of lidocine, the effects of $Labrasol^{(R)}$, $Labrafil^{(R)}$, $Labrafac^{(R)}$ and $Transcutol^{(R)}$ were investigated. The skin permeation of lidocaine was increased when $Labrasol^{(R)}$ and $Transcutol^{(R)}$ were used as permeation enhancer. To evaluate the influence of ultrasound, various factors such as application modes (continuous mode and pulsed mode), frequency (1.0 and 3.0 MHz) and intensity (1.0, 1.5 and 2.0 w/$cm^2$) were investigated with lidocaine hydrogel. The pronounced effect of ultrasound on the skin permeation of lidocaine was observed at all ultrasound energy levels. The influence of frequency having an effect on skin permeation rate was higher in the case of using 1 MHz, 2.0 w/$cm^2$ and continuous treatment. As the intensity of ultrasound increased, the permeation of lidocaine was accelerated. The in vivo anesthetic effects were evaluated by two aspects as mechanical threshold and electrical threshold. Six healthy volunteers consented to the randomized, double-blind, and cross-over designed study in each group. In each subject, 3 groups were adapted such as K group (ultrasound with gel base only), L group (lidocaine gel) and B group (ultrasound with lidocaine gel). In conclusion, lidocaine was potent anesthetic which could be block pain threshold effectively. And ultrasound could accelerate the skin penetration of lidocaine. The phonophoretic delivery system could be a good candidate for lidocaine as a local anaesthetic to improve the skin permeation and in vivo anaesthetic effect.

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References

  1. Kundu S. and Achar S., Reated Articles., Links., Principles of office anesthesia part II. Topical anesthesia. Am Fam Physician., 66(1), 99-102 (2002)
  2. Machet L. and Boucaud A., Phonophoresis effciency, mechanisms and skin tolerance, Science Direct, 243(1-2) 1-15 (2002)
  3. Jae-Hong Kim., Byung-chul Shin., Ho-Suk Choi., Sung-Soo Kim and Young-Do Park., Effect of Ionic Enhancers in the Iontophoresis of Lidocaine, J. Kor. Pharm. Sci., 29(3) 171-177 (1999)
  4. James E.F., Reynolds(Ed.)., The Royal Pharmaceutical Society of Great Britain, Martindale(30TH), The Pharmaceutical press, London, England, pp. 1010-1014 (1993)
  5. Stratford AF., Zoutman DE. and Davidson Js., Related Articles., Links., Effect of lidocaine and epinephrine on Staphylococcus aureus in a guinea pig model of surgical wound infection, Plast Reconstr Surg., 110(5), 1275-9 (2002) https://doi.org/10.1097/00006534-200210000-00010
  6. Williams AR., Related Articles., Links., Phonophoresis : an in vivo evaluation tsing three anaesthetic preparations, Ultrasonics., 28(3), 137-41(1990) https://doi.org/10.1016/0041-624X(90)90075-Y
  7. McElnay JC., Matthews MP., Harland R. and McCaferty DF., Related Articles., Links., The effect of ultrasound on the percutaneous absorption of lignocaine, Br J Clin Pharmacol., 20(4) 421-4 (1985) https://doi.org/10.1111/j.1365-2125.1985.tb05089.x
  8. Bronaugh RL, Maibach HI : Percutaneous absorption. Marcel Dekker, New York, 1-12 (1989)
  9. Schaefer H, Zesch A, Stuttgen G : Skin permeability. Springer-Verlag, New York (1982)
  10. Yong C.S., Rhee J.D. and Choi H.G., Factors affecting percutaneous absorption, The J.S.B.R., 2, 49-67 (2000)
  11. Riviere J.E. and Heit M.C., Electrically-assisted transdermal drug delivery, Pharm. Res., 14, 687-697 (1997) https://doi.org/10.1023/A:1012129801406
  12. Burnette RR : Iontophoresis in transdermal drug delivery. J Hadgraft and RH Cuy(eds.). Marcel Dekker, New York, 247-291 (1989)
  13. Ahn H.A., Transdermal delivery of cationic drug, isopropamide through rat skin by iontophoresis, Thesis of Pharm. Seoul Nati. Univ., (1991)
  14. Tyle P. and Agrawala P., Drug delivery by phonophoresis, Pharmaceutical Research, 6(5), 355-359 (1989) https://doi.org/10.1023/A:1015967012253
  15. Mitragotri S., Blankschtein D. and langer R., Transdermal drug delivery using low-frequency sonophoresis, Pharm. Res., 13, 411-420 (1996) https://doi.org/10.1023/A:1016096626810
  16. Bommannan, D., Okuyama H., Stauffer P., Guy R.H. and Sonophoresis. I. The use of high-frequency ultrasound to enhance transdermal drug delivery, Pharmaceutical Research,. 4(9), 559-564 (1992)
  17. Hoogland R., Ultrasound therapy, Instrument Manual. Enraf Nonius, Amsterdam, 14-17 (1991)
  18. Meidan VM., Walmsley AD., Socker MF. and Irwin WJ., Ultrasound-enhanced diffusion into coupling gel during phonophoresis of 5-fluorouracil, Int J Pharm., 185(2), 205-13 (1999) https://doi.org/10.1016/S0378-5173(99)00168-4
  19. Asano J., Suisha F., Takada M., Kawasaki N. and Miyazaki S., Effect of pulsed output ultrasund on the transdermal absorption of indomethacin from an ointment in rats, Biol pharm Bull., 20(3), 288-91 (1997) https://doi.org/10.1248/bpb.20.288
  20. Ueda H., Ogihara M., Sugibayashi K. and Morimoto Y., Difference in the enhancing effects of ultrasound on the skin permeation of polar and non-polar drugs, Chem pharm bull,. 44(10), 1973-6 (1996) https://doi.org/10.1248/cpb.44.1973
  21. Bare AC, McAnaw MB., Pritchard AE., Struebing JG., Smutok MA., Christie DS., Domenech MA., Bare MA., Bloodworth ML. and Seal La., Phonophoretic delivery of 10% hydrocortisone through the epidermis of humans as determined by serum cortisol concentrations, Phys Ther., 76(7), 738-45 (1996) https://doi.org/10.1093/ptj/76.7.738
  22. Franklin ME., Smith ST., Chenier TC. and Franklin RC., Effect of phonophoresis with dexamethasone on adrenal function, J Orthop sports Phys Ther,. 22(3),103-7 (1995) https://doi.org/10.1016/S8756-3282(98)00015-5
  23. Ciccone CD., Leggin BG. and Callamaro JJ., Effects of ultrasoumd and trolamine salicylate phonophoresis on delayde-onset muscle soreness. Phys Ther,. 71(9) 666-75 (1991) https://doi.org/10.1093/ptj/71.9.666a
  24. K.H.Chung, Y.I.Kim and J.H.Yang, Phonphoretic Delivery of Piroxicam., J.Kor.Pharm. sci., 32(4), 259-265(2002)
  25. K.S. Song, Y.I. Kim and J.H. Yang., Transdermal Delivery of Triamcinolone acetonide Gel by Ultrasound, J. Kor. Pharm. Sci., 32(2), 87-93 (2002)
  26. J.H.Yang, D.K.Kim, M.Y.Yun, T.Y.Kim and S.C.Shin., Transdermal Delivery System of Triamcinolone acetonide from a gel using Phonophoresis., Arch. Pharm. Res. 29(5), 412-417(2006) https://doi.org/10.1007/BF02968592
  27. Boucaud, A., Garrigue M.A., Machet L., Vallant L. and patat F., Effect of sonication parameters on transdermal delivery of insulin to hairless rats, J. Control. Release., 81, 113-119 (2002) https://doi.org/10.1016/S0168-3659(02)00054-8
  28. Boucaud A., Montharu J., Machet L., Arbeille B., Machet M. C., Sourmac M., Mavon A., Patat F. and Vaillant L., In vitro study of low-frequency ultrasound-enhanced transdermal trasport of fentanyl and caffeine across human and hairless rat skin, Int. J . Pharm., 228, 69-77 (2001) https://doi.org/10.1016/S0378-5173(01)00820-1
  29. Mitragotri S. and Kost J., Transdermal delivery of heparin and low-molecular weight heparin using low frequency ultrasound, Pharm.Res. 18, 1151-1156 (2001) https://doi.org/10.1023/A:1010979010907
  30. Barry B. W., Dermatological Formulations, Marcel Dekker, New York, 49-94 (1983)
  31. Hanne Gottrup, Jesper Nielsen, Lars Arendt-Nielsen and Troels S. Jensen, The realtionshop between sensory thresholds and mechanical hyperalgesia in nerve injury, pain, 75, 321-329 (1998) https://doi.org/10.1016/S0304-3959(98)00011-6
  32. Holger Holthusen., Stefan Irsfeld., Peter Lipfert. and Effect of pre- or post-traumatically applied i. v. lidocaine on primary and secondary hyperalgesia after experimantal heat trauma in humans, pain,. 88, 295-302 (2000) https://doi.org/10.1016/S0304-3959(00)00338-9
  33. Eva Kosek., Jan Ekholm. and Per Hansson., Modulation of pressure pain thresholds during and following isometric contraction in patients with fibromyalgia and in healthy controls, pain,. 64, 415-423 (1996) https://doi.org/10.1016/0304-3959(95)00112-3
  34. Johnson M. I., Hajela V.K., Ashton C.H. and Thompson J.W., The effects of auricular transcutaneous electrical nerve stimulation (TENS) on experimental pain thresholdl and autonomic function in healthy subjects, pain,. 46(3), 337-342 (1991) https://doi.org/10.1016/0304-3959(91)90116-F
  35. Rieb L. and Pomeranz B., Alterations in electrical pain thresholds by use of acupuncture- like transcutaneous electrical nerve stimulation in pain - free subjects, physical Therapy., 72(9), 658-667 (1992) https://doi.org/10.1093/ptj/72.9.658
  36. Parfilt K., Martinadale, 3rd edit., Pharmacentical Press, London, UK, 1281-1298 (1999)
  37. Turner W.M. Lidocaine and psychotic reactions, Ann In tern Med, 97, 149-150, (1982)
  38. Curley R.K. An unusual cutaneous reaction to lignocaine, Br Dent J 162. 113-114, (1987) https://doi.org/10.1038/sj.bdj.4806032
  39. Nussbaum E.L., Therapeutic ultrasound, Physical Agents Theory and Practice for The Physical Therapist Assistant, Yeongmun Publishing Company, Seoul, 95-102 (1996)
  40. Cameron M.H. and Monroe L.G., Relative transmission of ultrasound by media customarily used for phonophoresis, Phys. Ther., 72, 142-148 (1992) https://doi.org/10.1093/ptj/72.2.142
  41. Dinno M.A., Dyson M., Young S.R., Mortimer A.J., Hart J. and Crum L.A., The significance of membrane changes in the safe and effective use of therapeutic and diagnostic ultrasound, Phys. Med. Biol., 34(11), 1543-1552 (1989) https://doi.org/10.1088/0031-9155/34/11/003
  42. Prithriruj P., Practical management of pain Vol. 2, Year book medical publishers Inc. Chicago, (1986)
  43. Thomson I, Addition of hyaluronate to lignocaine with adrenaline for retrobulbar anaesthesia in the surgery of senile cataract. Br J Ophthalomol, 72, 700-702, (1988) https://doi.org/10.1136/bjo.72.9.700