Skip to main content

Enhancedex vivo buccal transport of propranolol: Evaluation of phospholipids as permeation enhancers

Abstract

The aim of the present study was to evaluate the effects of two phospholipid permeation enhancers, lysophosphatidylcholine (LPC) and didecanoylphosphatidylcholine (DDPC), along with a fusidic acid derivative, sodium taurodihydrofusidate (STDHF) and ethanol (EtOH) on the buccal transport of propranolol hydrochloride (PPL) using anex vivo buccal diffusion model. The permeation rate of [3H]PPL as measured by steady-state fluxes increased with increasing EtOH concentration. A significant flux enhancement (P<0.05) was achieved by EtOH at 20 and 30 %v/v concentrations. At a 0.5 %w/v permeation enhancer concentration, the buccal permeation of [3H]PPL was significantly enhanced by all the enhancers studied (i.e., LPC, DDPC and STDHF) compared to the control (phosphate-buffered saline pH 7.4, PBS). LPC and DDPC displayed a greater degree of permeation enhancement compared with STDHF and EtOH-PBS mixtures with an enhancement ratio of 3.2 and 2.9 for LPC and DDPC, respectively compared with 2.0 and 1.5 for STDHF and EtOH:PBS 30:70 %v/v mixture, respectively. There was no significant difference between LPC and DDPC for the flux values and apparent permeability coefficients of [3H]PPL. These results suggest that phospholipids are suitable as permeation enhancers for the buccal delivery of drugs.

This is a preview of subscription content, access via your institution.

References

  • Anders, R. and Merkle, H. P., Evaluation of laminated muco- adhesive patches for buccal drug delivery.Int. J. Pharm., 49, 231–240 (1989).

    Article  CAS  Google Scholar 

  • Aungst, B. J., Rogers, N. J., and Shefter, E., Comparison of nasal, rectal, buccal, sublingual and intramuscular insulin efficacy and the effects of a bile salt absorption promoter.J. Pharmacol. Exp. Ther., 24, 23–27 (1988).

    Google Scholar 

  • Aungst, B. J. and Rogers, N. J., Comparison of the effects of various transmucosal absorption promoters on buccal insulin delivery.Int. J. Pharm., 53, 227–235 (1989).

    Article  CAS  Google Scholar 

  • Bolin, T., Franzen, L., Sjodahl, R., and Tagesson, C., Passage of molecules through the wall of the gastrointestinal tract.Scand. J. Gastroenterol., 21, 441–448 (1986).

    PubMed  Article  CAS  Google Scholar 

  • Chidambaram, N. and Srivatsava, A. K., Buccal drug delivery systems.Drug Dev. Ind. Pharm., 21, 1009–1036 (1995).

    Article  CAS  Google Scholar 

  • Cid, E., Mella, R., Lucchini, L., Carcamo, M., and Monasterio, J., Plasma concentrations and bioavailability of propranolol by oral, rectal and intravenous administration in man.Biopharm. Drug Dispos., 7, 559–566 (1986).

    PubMed  Article  CAS  Google Scholar 

  • Coutel-Egros, A., Maitani, Y., Veillard, M., Machida, Y., and Nagai, T., Combined effects of pH, cosolvent and penetration enhancers on thein vitro buccal absorption of propranolol through excised hamster cheek pouch.Int. J. Pharm., 84, 117–128 (1992).

    Article  CAS  Google Scholar 

  • DeGrande, G., Benes, L., Horriere, F., Karsenty, H., Lacoste, C., McQuinn, R., Gou, J.-H., and Scherrer, R., Specialized oral mucosal drug delivery systems: Patches, In Rathbone, M. J. (Eds.). Oral Mucosal Drug Delivery. Marcel Dekker, New York, pp. 285–317, (1996).

    Google Scholar 

  • De Vries, M. E., Bodde, H. E., Verhoef, J. C., and Junginger, H. E., Developments in buccal drug delivery.Crit. Rev. Therap. Drug Can. Syst., 8, 271–303 (1991).

    Google Scholar 

  • Dowty, M. E., Knuth, K. E., Irons, B. K., and Robinson, J. R., Transport of thyrotropin releasing hormone in rabbit buccal mucosain vitro.Pharm. Res., 9, 1113–1122 (1992).

    PubMed  Article  CAS  Google Scholar 

  • Risher, A. N., Farraj, N. P., OHagan, D. T., Jabbal-Gill, I., Johansen, B. R., Davis, S. S., and Illum, L., Effect of L-α- lysophosphatidylcholine on the nasal absorption of human growth hormone in three animal species.Int. J. Pharm., 74, 147–156 (1991).

    Article  Google Scholar 

  • Ganem-Quintanar, A., Kalia, Y. N., Falson-Rieg, P., and Buri, P., Mechanism of oral permeation enhancement.Int. J. Pharm., 156, 127–142 (1997).

    Article  CAS  Google Scholar 

  • Harris, D. and Robinson, J. R., Drug delivery via the mucous membranes of the oral cavity.J. Pharm. Sci., 81, 1–10 (1992).

    PubMed  Article  CAS  Google Scholar 

  • Hermens, W. A. J. J., Hooymans, P. M., Verhoef, J. C., and Merkus, R. W. H. M., Effects of absorption enhancers on human nasal tissue ciliary movement in vitro.Pharm. Res., 7, 144–146 (1990).

    PubMed  Article  CAS  Google Scholar 

  • Hirai, S., Yashiki, T., and Mima, H., Effect of surfactants on the nasal absorption of insulin in rats.Int. J. Pharm., 9, 165–172 (1981).

    Article  CAS  Google Scholar 

  • Hovgaard, L., Brøndsted, H., and Nielsen, H. M., Drug delivery studies in Caco-2 monolayers. II. Absorption enhancer effects of lysophosphatidylcholines.Int. J. Pharm., 114, 141–149 (1995).

    Article  CAS  Google Scholar 

  • Iwamoto, K. and Watanabe, J., Dose-dependent presystemic elimination of propranolol due to hepatic first-pass metabolism in rats.J. Pharm. Pharmacol., 37, 826–828 (1985).

    PubMed  CAS  Google Scholar 

  • Kissel, T., Drewe, J., Bantle, S., Rummelt, A., and Beglinger, C., Tolerability and absorption enhancement of intranasally administered octreotide by sodium taurodihydrofusidate in healthy subjects.Pharm. Res., 9, 52–57 (1992).

    PubMed  Article  CAS  Google Scholar 

  • Le Brun, P. P. H., Fox, P. L. A., De Vries, M. E., and Boddé, H. E.,In vitro penetration of some β-adrenoreceptor blocking drugs through porcine buccal mucosa.Int. J. Pharm., 49, 141–145 (1989).

    Article  Google Scholar 

  • Lee, J. and Kellaway, I. W., Buccal permeation of [D-Ala2, D-Leu5]enkephalin from liquid crystalline phases of glyceryl monooleate.Int. J. Pharm., 195, 35–38 (2000).

    PubMed  Article  CAS  Google Scholar 

  • Lee, J., Lee, S. K., and Choi, Y. W., The effect of storage conditions on the permeability of porcine buccal mucosa.Arch. Pharm. Res., 25, 546–549 (2002).

    PubMed  CAS  Article  Google Scholar 

  • Parfitt, K., Martindale (32nd edition). Pharmaceutical Press, London, (1999).

    Google Scholar 

  • Richardson, J. L., Minhas, P. S., Thomas, N. W., and Illum, L., Vaginal administration of gentamicin to rats. Pharmaceutical and morphological studies using absorption enhancers.Int. J. Pharm., 56, 29–35 (1989).

    Article  CAS  Google Scholar 

  • Schürmann, W. and Turner, P., A membrane model of the human oral mucosa as derived from buccal absorption performance and physicochemical properties of the β-blocking drugs atenolol and propranolol.J. Pharm. Pharmacol., 30, 137–147 (1978).

    PubMed  Google Scholar 

  • Senel, S. and Hincal, A. A., Drug permeation enhancement via buccal route: possibilities and limitations.J. Control. Rel., 72, 133–144 (2001).

    Article  CAS  Google Scholar 

  • Shand, D. G., Nickolis, E. M., and Oates, J. A., Plasma propranolol levels in adults with observation in four children.Clin. Pharmacol. Ther, 11, 112–118 (1970).

    PubMed  CAS  Google Scholar 

  • Vermehren, C. and Hansen, H. S., Shape changes in the erythrocyte membrane induced by the absorption enhancer didecanoylphosphatidylcholine.Int. J. Pharm., 174, 1–8 (1998).

    Article  CAS  Google Scholar 

  • Walle, T., Conradi, E. C., Walle, U. K., Pagan, T. C., and Gaffney, T. E., The predictable relationship between plasma levels and dose during chronic propranolol therapy.Clin. Pharmacol. Ther., 24, 668–677 (1978).

    PubMed  CAS  Google Scholar 

  • Wertz, P. W. and Squier, C. A., Cellular and molecular basis of barrier function in oral epithelium.Crit. Rev. Therap. Drug Carr. Syst, 8, 237–269 (1991).

    CAS  Google Scholar 

  • Zhang, J., Niu, S., Ebert, C., and Stanley, T. H., Anin vivo dog model for studying recovery kinetics of the buccal mucosa permeation barrier after exposure to permeation enhancers: apparent evidence of effective enhancement without tissue damage.Int. J. Pharm., 101, 15–22 (1994).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jaehwi Lee.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Lee, J., Choi, Y.W. Enhancedex vivo buccal transport of propranolol: Evaluation of phospholipids as permeation enhancers. Arch Pharm Res 26, 421 (2003). https://doi.org/10.1007/BF02976701

Download citation

  • Received:

  • DOI: https://doi.org/10.1007/BF02976701

Key words

  • Buccal delivery
  • Propranolol
  • Permeation enhancer
  • Lysophosphatidylcholine
  • Didecanoylphosphatidylcholine
  • Sodium taurodihydrofusidate