YAKHAK HOEJI (약학회지)

The Pharmaceutical Society of Korea (대한약학회)
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Effects of Vehicles and Enhancers on the Permeation Properties of Tizanidine Hydrochloride through Strat-MMTM Artificial Membrane and Hairless Mouse Skin

용제와 투과촉진제가 Strat-MTM 인공막 및 무모마우스 피부를 통한 티자니딘염산염의 투과 특성에 미치는 영향

  • 박명신 (동덕여자대학교 약학대학) ;
  • 전인구 (동덕여자대학교 약학대학)
  • Received : 2016.01.15
  • Accepted : 2016.02.19
  • Published : 2016.02.29
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Abstract

This study was aimed to enhance the percutaneous absorption of tizanidine hydrochloride (TZ) across Strat-M$^{TM}$ artificial membrane and excised hairless mouse skin using various vehicles and chemical permeation enhancers. Solubility studies were performed using hydrophilic and lipophilic vehicles. To initially evaluate vehicle effects on skin permeation, Strat-M$^{TM}$ membrane was adopted using Franz-type diffusion cells loaded with 0.4 mg donor dose. Effects of fatty acids on the permeation of TZ from PG and PGMC were compared, and the effects of various hydrophilic vehicles in the presence of linoleic acid were studied using excised hairless mouse skin specimens. The mean solubility (mg/ml) of TZ in hydrophilic vehicles was higher: water > PG > DMSO > ethanol > PEG 200 > NMP > PEG 300 > PEG 400 > DGME, and solubilities in lipophilic vehicles such as PGMC, PGMC, IPM, Captex 200 and Captex 300 were much less than 1.0 mg/ml. Permeation rates through StratTM membrane from pure vehicles were in the rank order: PGMC ${\geq}$ LBF > DMSO ${\geq}$ NMP ${\geq}$ PGML ${\geq}$ PG ${\geq}$ PEG 200 ${\geq}$ DGME ${\geq}$ EtOH. However, permeation rates of TZ through hairless mouse skin from pure vehicles were very low, although PG showed the highest flux ($1.66{\pm}0.28{\mu}g/cm^2{\cdot}hr$). Therefore, PG was selected in further studies. Addition of enhancers (3 v/v%) into PG markedly increased the flux (${\mu}g/cm^2{\cdot}hr$): oleyl alcohol ($14.9{\pm}3.1$) ${\geq}$ oleic acid ($14.5{\pm}1.6$) ${\geq}$ linoleic acid ($13.7{\pm}1.3$) > capric acid ($4.4{\pm}0.6$) > caprylic acid ($2.1{\pm}0.4$). Among hydrophilic vehicles with linoleic acid, PG and DMSO revealed relatively higher permeation for TZ. Increase of donor dose in PG resulted in dose-dependent permeation fluxes. These results suggest that permeation properties of TZ from nonaqueous solutions are markedly different between Strat-$M^{TM}$ membrane and excised hairless mouse skin, and transdermal delivery of TZ would be feasible with a combination of PG and enhancers.

Keywords

References

  1. Wagstaff, A. J. and Bryson, H. M. : Tizanidine. A review of its pharmacology, clinical efficacy and tolerability in the management of spasticity associated with cerebral and spinal disorders. Drugs 53, 435 (1997). https://doi.org/10.2165/00003495-199753030-00007
  2. Lawson, K. : Tizanidine: a therapeutic weapon for spasticity? Physiother. 84, 418 (1998). https://doi.org/10.1016/S0031-9406(05)65839-7
  3. Westfall, T. C. and Westfall, D. P. : Adrenergic agonists and antagonists. In: Brunton, L. L., ed. Goodmann and Gilman, The Pharmacological Basis of Therapeutics. New York, Mc Graw-Hill Medical Publishing Division, pp. 237-295 (2005).
  4. Shah, J., Wesnes, K. A., Kovelesky, R. A. and Henney, H. R. 3rd. : Effects of food on the single-dose pharmacokinetics/ pharmacodynamics of tizanidine capsules and tablets in healthy volunteers. Clin. Ther. 28, 1308 (2006). https://doi.org/10.1016/j.clinthera.2006.09.014
  5. Henney, H. R. and Shah, J. : Relative bioavailability of tizanidine 4-mg capsule and tablet formulations after a standardized highfat meal: a single-dose, randomized, open-label, crossover study in healthy subjects. Clin. Ther. 29, 661 (2007). https://doi.org/10.1016/j.clinthera.2007.04.012
  6. Henney, H. R. 3rd, Fitzpatrick, A., Stewart, J. and Runyan, J. D. : Relative bioavailability of tizanidine hydrochloride capsule formulation compared with capsule contents administered in applesauce: a single-dose, open-label, randomized, two-way, crossover study in fasted healthy adult subjects. Clin Ther. 30, 2263 (2008). https://doi.org/10.1016/j.clinthera.2008.12.014
  7. Momo, K., Homma, M., Osaka, Y., Inomata, S., Tanaka, M. and Kohda, Y. : Effects of mexiletine, a CYP1A2 inhibitor, on tizanidine pharmacokinetics and pharmacodynamics. J. Clin. Pharmacol. 50, 331 (2010). https://doi.org/10.1177/0091270009341961
  8. Shanker, G., Kumar, C. K., Gonugunta, C. S. R., Kumar, B. V. and Veerareddy, P. R. : Formulation and evaluation of bioadhesive buccal drug delivery of tizanidine hydrochloride tablets. AAPS PharmSciTech 10, 530 (2009). https://doi.org/10.1208/s12249-009-9241-2
  9. Vakhapova, V., Auriel, E. and Karni, A. : Nightly sublingual tizanidine HCl in multiple sclerosis: clinical efficacy and safety. Clin. Neuropharmacol. 33, 151 (2010). https://doi.org/10.1097/WNF.0b013e3181daad7d
  10. Pendekal, M. S. and Tegginamat, P. K. : Formulation and evaluation of a bioadhesive patch for buccal delivery of tizanidine, Acta Pharm. Sin. B 2, 318 (2012). https://doi.org/10.1016/j.apsb.2011.12.012
  11. Kulkarni, G. S. and Sateesh Babu, P. R. : Design and evaulation of tizanidine buccal mucoadhesive patches. J. Appl. Pharm. Sci. 2, 74 (2012).
  12. El-Mahrouk, G. M., El-Gazayerly, O. N., Aboelwafa, A. A. and Taha, M. S. : Chitosan lactate wafer as a platform for the buccal delivery of tizanidine HCl: In vitro and in vivo performance. Int. J. Pharm. 467, 100 (2014). https://doi.org/10.1016/j.ijpharm.2014.03.049
  13. Pulgamwar, G. V., Pentewar, R. S., Bharti, R. U., Bhosle, P. H., Kazi, S. N. and Inamdar, N. A. : Development and characterization of mucoadhesive drug delivery system of tizanidine hydrochloride, Asian J. Pharm. Tech. Innov. 3, 1 (2015).
  14. Patel, D., Naik, S. and Misra, A. : Improved transnasal transport and brain uptake of tizanidine HCl-loaded thiolated chitosan nanoparticles for alleviation of pain. J. Pharm. Sci. 101, 690 (2012). https://doi.org/10.1002/jps.22780
  15. Vitale, D. C., Piazza, C., Sinagra, T., Urso, V., Cardì, F., Drago, F. and Salomone, S. : Pharmacokinetic characterization of tizanidine nasal spray, a novel intranasal delivery method for the treatment of skeletal muscle spasm. Clin. Drug Investig. 33, 885 (2013). https://doi.org/10.1007/s40261-013-0137-2
  16. Mutalik, S., Parekha, H. S., Daviesa, N. M. and Udupa, N. : A combined approach of chemical enhancers and sonophoresis for the transdermal delivery of tizanidine hydrochloride. Drug Del. 16, 82 (2009). https://doi.org/10.1080/10717540802605053
  17. Trivedi, S. U., Sudhakar, C. K. and Jain, S. : Transdermal administration of tizanidine hydrochloride using elastic vesicles: characterization and in vitro permeation studies. Asian J. Pharm. Sci. Res. 3, 29 (2013).
  18. Sandhya Rani, G., Supraja, N. and Ratnakar, A. : Formulation and evaluation of tizanidine hydrochloride transdermal patches. Int. J. Adv. Pharm. 4, 64 (2014).
  19. Nagadevi, B., Kumar, K. S., Venkanna, P. and Prabhakar, D. : Formulation and characterisation of tizanidine hydrochloride loaded ethosomes patch. Int. J. Pharm. Pharm. Sci. 6, 199 (2014).
  20. Abdel Azim, A. M., El-Ashmoony, M., Swealem, A. M. and Shoukry, R. A. : Transdermal films containing tizanidine: in vitro and in vivo evaluation. J. Drug Del. Sci. Tech. 24, 92 (2014). https://doi.org/10.1016/S1773-2247(14)50013-5
  21. Uchida, T., Kadhum, W. R., Kanai, S., Todo, H., Oshizaka, T. and Sugibayashi, K. : Prediction of skin permeation by chemical compounds using the artificial membrane, $Strat-M^{TM}$. Eur. J. Pharm. Sci. 67, 113 (2015). https://doi.org/10.1016/j.ejps.2014.11.002
  22. Gwak, H. S. and Chun, I. K. : Effect of vehicles and penetration enhancers on the in vitro percutaneous absorption of tenoxicam through hairless mouse skin. Int. J. Pharm. 236, 57 (2002). https://doi.org/10.1016/S0378-5173(02)00009-1
  23. Lee, J. H. and Chun, I. K. : Effects of various vehicles and fatty acids on the skin permeation of lornoxicam. J. Pharm. Invest. 42, 235 (2012). https://doi.org/10.1007/s40005-012-0035-2
  24. Qi, M. L., Wang, P. and Wang, L. : Validated liquid chromatography method for assay of tizanidine in drug substance and formulated products. Anal. Chim. Acta 478, 171 (2003). https://doi.org/10.1016/S0003-2670(02)01525-8
  25. Kaul, N., Dhaneshwar, S. R., Agrawal, H., Kakad, A. and Patil, B. : Application of HPLC and HPTLC for the simulataneous determination of tizanidine and rofecoxib in pharmaceutical dosage form. J. Pharm. Biomed. Anal. 37, 27 (2005). https://doi.org/10.1016/j.jpba.2004.09.036
  26. Gandhimathi, M., Ravi, T. K. and Varghese, S. J. : Simultaneous LC determination of tizanidine and rofecoxib in tablets. J. Pharm. Biomed. Anal. 37, 183 (2005). https://doi.org/10.1016/j.jpba.2004.09.039
  27. Hatanaka, T., Inuma, M., Sugibayashi, K. and Morimoto, Y. : Prediction of skin permeability of drugs. I. Comparison with artificial membrane. Chem. Pharm. Bull. 38, 3452 (1990). https://doi.org/10.1248/cpb.38.3452
  28. Ansari, M., Kasemipour, M. and Akalamli, M. : The study of drug permation through natural membrane. Int. J. Pharm. 327, 6 (2006). https://doi.org/10.1016/j.ijpharm.2006.07.034
  29. Kano, S., Todo, H., Sugie, K., Fujimoto, H., Nakada, K., Tokudome, Y., Hashimoto, F. and Sugibayashi, H. : Utilization of reconstructed cultured human skin models as an alternative skin for permeation studies of chemical compounds. Alter. Animal Test Exp. 15, 61 (2010).
  30. Miki, R., Ichitsuka, Y., Yamada, T., Kimura, S., Egawa, Y., Seki, T., Juni, K., Ueda, H. and Morimoto, Y. : Development of a membrane impregnated with a poly(dimethylsiloxane)/ poly(ethylene glycol) copolymer for a high-throughput screening of the permeability of drugs, cosmetics, and other chemicals across the human skin. Eur. J. Pharm. Sci. 66, 41 (2015). https://doi.org/10.1016/j.ejps.2014.09.024
  31. Sri Janani, N., Bharath Kumar, G., Balakrishna, P., Sruthi, D., Srujan Kumar, M. and Mantry, S. : A review on Strat-M membrane. Int. J. Innov. Pharm. Sci. Res. 2, 962 (2014).
  32. Barry, B. W. : Dermatological Formulations, Marcel Dekker, New York, pp. 1-48 (1983).
  33. Golden, G. M., McKie, J. E. and Potts, R. O. : Role of stratum corneum lipid fluidity in transdermal drug flux. J. Pharm. Sci. 76, 25 (1987). https://doi.org/10.1002/jps.2600760108
  34. Komata, Y., Kaneko, A. and Fujie, T. : In vitro percutaneous absorption of thiamine disulfide through rat skin from a mixture of propylene glycol and fatty acid or its analog. Chem. Pharm. Bull. 40, 2173 (1992). https://doi.org/10.1248/cpb.40.2173
  35. Moffat, A. C., Osselton, M. D. and Widdop, B. Clarke's Analysis of Drugs and Poisons, 2nd Vol., 3rd ed., London, Pharmaceutical Press (2006).
  36. Jeans, C. W. and Heard, C. M. : A therapeutic dose of primaquine can be delivered across excised human skin from simple transdermal patches. Int. J. Pharm. 189, 1 (1999). https://doi.org/10.1016/S0378-5173(99)00215-X