Journal of Pharmaceutical Investigation

The Korean Society of Pharmaceutical Sciences and Technology (한국약제학회)
권호 표지
DOI QR코드

DOI QR Code

Buccal Transport of Paclitaxel using Ethanol and Glyceryl Monooleate

  • Published : 2007.10.21
Download PDF
⟨ Previous Next ⟩

Abstract

Paclitaxel (PTX) is an antineoplastic agent approved for the treatment of ovarian and breast carcinomas. However, the use of paclitaxel as an anticancer drug is limited by its extremely poor water solubility (below $0.3\;{\mu}g/mL$). Furthermore, it has very low bioavailability when administered orally because paclitaxel is a substrate of P-glycoprotein (P-gp) efflux pump. In this study, buccal delivery of PTX was investigated as one of the alternatives for PTX delivery. Ethanol and glyceryl monooleate (GMO) were selected as permeation enhancing agents to increase solubility and permeation across buccal mucosa of PTX. At the different concentrations of ethanol solution ($30{\sim}70\;w/w\;%$), PTX permeation was studied, followed effects of GMO in the concentration range of $2.5{\sim}25%$ with ethanol vesicle. The transbuccal ability of PTX was evaluated in vitro using Franz diffusion cells mounted with rabbit buccal mucosa. As a result, incorporation of PTX into ethanol vesicle with GMO significantly enhanced the PTX permeation in rabbit buccal mucosa. Particularly, the mixtures of ethanol:water:GMO at the ratio of 50:47.5:2.5 showed the most excellent enhancing ability. The results showed a promising possibility for buccal delivery of PTX.

Keywords

References

  1. M.C. Wani, H.L. Tayler, M.E. Wall, P. Coggom and A.T. McPhail, Plant antitumor agents. Part VI. The isolation and structure of tazeol, a novel antileukemic and antitumor agent from Taxus brevifolia, J. Am. Chem. Soc., 93, 2325-2327 (1971) https://doi.org/10.1021/ja00738a045
  2. E. Rowinsky and R.C. Donehower, Paclitaxel (Taxol), N. Engl. J. Med., 332, 1004-1014 (1995) https://doi.org/10.1056/NEJM199504133321507
  3. N. Kumar, Taxol-induced polymerization of purified tubulin. Mechanism of action, J. Biol. Chem., 256, 10435-10441 (1981)
  4. J.J. Mnafedi and S.B. Horwitz, An antimitotic agent with a new mechanism of action, Pharmacal. Ther., 25, 83-125 (1984) https://doi.org/10.1016/0163-7258(84)90025-1
  5. Feng and G. Huang, Effects of emulsifiers on the controlled release of paclitaxel $(Taxol^{TM})$ from nanospheres of biodegradable polymers, J. Controlled Rel., 71, 53-69 (2001) https://doi.org/10.1016/S0168-3659(00)00364-3
  6. K.W. Garren, E.M. Top, A J. Repta, Buccal absorption, simultaneous diffusion and metabolism of an aminopeptidase substrate in the hamster cheek pouch, Pharm. Res., 6, 966-970 (1989) https://doi.org/10.1023/A:1015949614437
  7. A Relnhold and P.M. Haus, Evaluation of laminated mucoadhesive patches for buccal drug delivery, Int. J. Pharm., 49, 231-237 (1989) https://doi.org/10.1016/0378-5173(89)90347-5
  8. D. Harris and J.R. Robinson, Drug delivery via the mucous membrane of the oral cavity, J. Pharm. Sci., 81, 1-8 (1992) https://doi.org/10.1002/jps.2600810102
  9. S.P. Vyas and C.P. Jain, Bioadhesive polymer grafted starch microspheres bearing isosorbide dinitrate for buccal administration, J. Microencapsulation, 9, 457-464 (1992) https://doi.org/10.3109/02652049209040484
  10. B. Valenzuela, A Nacher, P. Ruiz-Carretero, A. Martin- Villodre, G. Lopez-Carballo and D. Barettino, Profile of p-glycoprotein distribution in the rat and its possible influence on the salbutamol intestinal absorption process, J. Pharm. Sci., 93, 1641-1648 (2004) https://doi.org/10.1002/jps.20071
  11. C.L. Cummins, D. Imbert, L.Z. Benet and C. Cullander, Assessment of enzymetic and transporter activity in the porcine buccal mucosa, AAPS Annual Meeting Proceed., Abstract 1167 (1998)
  12. T. Kai, Y.H.W. Mak, R.O. Potts and R.H. Guy, Mechanism of percutaneous penetration enhancement: effect of n-alkanols on the permeability barrier of hairless mouse skin, J. Control. Release, 12, 103-112 (1990) https://doi.org/10.1016/0168-3659(90)90086-9
  13. O. Pillai, Y. Nair and R. Panchagnula, Transdermal iontophoresis of insulin: Iv. Influence of chemical enhancers, Int. J. Pharm., 269, 109-120 (2004) https://doi.org/10.1016/j.ijpharm.2003.09.032
  14. P.B. Geraghty, D. Attwood, J.H. Collett and Y. Dandiker, The in vitro release of some antimuscarinic drugs from monooleinl water lyotropic liquid crystalline gels, Pharm. Res., 13, 1265-1271 (1996) https://doi.org/10.1023/A:1016036908947
  15. A. Ganem-Quintanar, D. Quintanar-Guerrero and P. Boo, Monoolein: a review of the pharmaceutical applications, Drug. Dev. Ind. Pharm., 26, 809-820 (2000) https://doi.org/10.1081/DDC-100101304
  16. R. He, D.Q.M. Craig, Characterization of the effects of drug addition on the structure of glyceryl monooleinlwater gel systems using low frequency dielectric spectroscopy, J. Pharm. Sci., 88, 635-639 (1999) https://doi.org/10.1021/js980251u
  17. K.B. Bhatia, S. Gao, T.P. Freeman and J. Singh, Effect of penetration enhancers and iontophoresis on the ultrastructure and cholecystokinin-8 permeability through porcine skin, J. Pharm. Sci., 86, 462-465 (1987)
  18. H. Smyth, G. Becket and S. Mehta, Effect of permeation enhancer pretreatment on the iontophoresis of luteinizing hormone releasing hormone (LHRH) through human epidermal membrane (HEM), J. Pharm. Sci., 91, 1296-1307 (2002) https://doi.org/10.1002/jps.10132
  19. T. Ogiso, M. Iwaki and T. Paku, Effects of various enhancers on transdermal penetration of indomethacin and urea, and relationship between penetration parameters and enhancement factors, J. Pharm. Sci., 84, 482-488 (1995) https://doi.org/10.1002/jps.2600840418
  20. G. R. PeRelra, J.H. Collett, S.B. Garcia, J.A Thomazini and M.Y.L.B. Bentley, Glycerol monooleate/solvents systems for progesterone transdermal delivery: in vitro permeation and microscopic studies, Braz. J. Pharm. Sci., 38, 55-62 (2002)
  21. J. Lee, S.C. Lee, G. Archarya, C. Chang and .K Park, Hydrotropic solubilization of Paclitaxel: Analysis of chemical structures for hydrotropic property, Pharm. Res., 20, 7, 1022-1030 (2003) https://doi.org/10.1023/A:1024458206032
  22. K. Ikegami, K. Tagawa, M. Kobayashi and T. Osawa, Prediction of in vivo drug release behavior of controlled-release multiple-unit dosage forms in dogs using a flow-through type dissolution test method, Int. J. Pharm., 258, 31-43 (2003) https://doi.org/10.1016/S0378-5173(03)00160-1
  23. N.M. Howie, T.K. Trigkas, A.T. Cruchley, P.W. Wertz, C.A. Squier and D.M. Williams, Short-term exposure to alcohol increases the permeability of human oral mucosa, Oral. Dis., 7, 349-354 (2001) https://doi.org/10.1034/j.1601-0825.2001.00731.x
  24. L.B. Lopes, J.H. Collett, M. Victoria and L.B. Bently, Topical delivery of cyclosporin A: an in vitro study using monoolein as a penetration enhancer, Eurp. J. Pharm. Biopharm., 60, 25-30 (2005) https://doi.org/10.1016/j.ejpb.2004.12.003