Transbuccal delivery of salbutamol sulphate: In vitro determination of routes of buccal transport

Authors

  • VB SUTARIYA Pharmacy Department. Center of relevance and excellence in NDDS. G.H. Patel building. The M.S. University of Baroda. Kalabhavan, Vadodar
  • RC MASHRU Pharmacy Department. Center of relevance and excellence in NDDS. G.H. Patel building. The M.S. University of Baroda. Kalabhavan, Vadodar
  • MG SANKALIA Pharmacy Department. Center of relevance and excellence in NDDS. G.H. Patel building. The M.S. University of Baroda. Kalabhavan, Vadodar
  • JM SANKALIA Pharmacy Department. Center of relevance and excellence in NDDS. G.H. Patel building. The M.S. University of Baroda. Kalabhavan, Vadodar

Keywords:

Permeability, Mucous membrane, Ionized species, Unionized species

Abstract

The influence of drug concentration, pH in donor chamber, and 1-octanol/buffer partition coefficient ontransbuccal permeation of salbutamol sulphate (pKa1 = 9.3, pKa2 = 10.3) across porcine buccal mucosawas studied by using in-line franz type diffusion cell at 37ºC. The pH was adjusted to several values,and the solubility of the drug in different pH was measured. Solubility of salbutamol sulphate decreasedwith increasing the pH. The permeability of the drug was evaluated at different donor pH and drugconcentrations. Permeability of unionized (Pu) and ionized (Pi) species of drug was calculated. Thesteady state flux increased linearly with the donor concentration (r2=0.9683) at pH 7.4. The permeabilityand the partition coefficient increased with increasing pH. The value of Pu and Pi of salbutamol sulphatewere 8.89 · 10-6 cm·s-1 and 2.49 · 10-6 cm·s-1 respectively. The total permeability coefficient increasedwith increasing the fraction of unionized form of the drug. The drug permeated through buccal mucosaby a passive diffusion process. The partition coefficient and pH dependency of drug permeabilityindicated that salbutamol sulphate was transported mainly via the paracellular route by a partitionmechanism.

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References

Gandhi RB, Robinson JR. Oral cavity as a site for bioadhesive drug delivery. Adv Drug Deli Rev 1994; 13: 43-74.

Patterson KW, Keane PW. Use of the buccal route for the administration of an antiemetic. Pharm Res 1989; 6: 160-166.

Rathbone MJ, Hasgraft J. Absorption of drugs from the human oral cavity. Int J Pharm 1991; 71: 9-24.

Khanvilkar K, Donovan MD, Flanagan DR. Drug transfer through mucus. Adv Drug Del Rev 2001; 48: 173-193.

Senel S, Hincal AA. Drug permeation enhancement via buccal route: possibilities and limitations. J Contr Rel 2001; 72: 133-144.

Junginger HE, Hoogstraate JA, Verhoef JC. Recent advances in buccal drug delivery and absorption—in vitro and in vivo studies. J Contr Rel 1999; 62: 149-159.

Chen LL, Chetty DJ, Chien YW. A mechanistic analysis to characterize oramucosal permeation properties. Int J Pharm 1999; 184: 63-72.

Al-sayed-omar O, Johnson A, Turner P. Influence of pH on the buccal absorption of morphine sulphate and its major metabolite, morphine-3-glucuronide. J Pharm Pharmcol 1987; 39: 934-935.

Nair MK, Chetty DJ, Ho H, Chein YW. Biomembrane permeation of nicotine: mechanistic studies with porcine mucosa and skin. J Pharm Sci 1997; 86: 257-262.

Nielson MN, Rassing MR. Nicotine permeability across the buccal TR 146 cell culture model and porcine mucosa in vitro: effect of pH and concentration. Eur J Pharm Sci 2002; 16: 151-157.

Deneer VH, Drese GB, Roemele PE, Verhoef JC, Lie-A-Huen L, Kingma JH, Brouwers JR, Junginger HE. Buccal transport of flecainide and sotalol: effect of a bile salt and ionization state. Int J Pharm 2002; 241: 127-134.

Coutel-Egros A, Maitani Y, Veillard M, Machida Y, Nagai T. Combined effects of pH, cosolvent and penetration enhancers on the in vitro buccal absorption of propanolol through excised hamster cheek pouch. Int J Pharm 1992; 84: 117-128.

Nielsen HM, Rassing MR. TR146 cells grown on filters as a model of human buccal epithelium: III. Permeability enhancement by different pH value, different osmolarity value, and bile salts. Int J Pharm 1999; 185: 215-225.

Gandhi RB, Robinson JR. Mechanisms of penetration enhancement for transbuccal delivery of salicylic acid. Int J Pharm 1992; 85: 129-140.

Shojaei AH, Berner B, Li X. Transbuccal delivery of acyclovir: I. in vitro determination of buccal transport. Pharm Res 1998; 15: 1182-1188.

Beckett AH, Moffat AC. Correlation of partition coefficients in n-heptane –aqueous systems with buccal absorption data for a series of amines and acids. J Pharm Pharmcol 1969; 21: Suppl 144S-150S.

Beckett AH, Triggs EJ. Buccal absorption of basic drugs and its application as an in vivo model passive drug transfer through lipid membrane. J Pharm Pharmcol 1967; 19: Suppl 31S-41S.

Le Brun PPH, Fox PLA, De Vries ME, Bodde HE. In vitro penetration of some â-adrenoreceptor blocking drugs through porcine buccal mucosa. Int J Pharm 1989; 49: 141-145.

Chen L, Hui-Nan X, Xiao-Ling L. In vitro permeation of tetramethylpyrazine across porcine buccal mucosa. Acta Pharmacol Sin 2002; 23: 792-796.

Garren KW, Repta AJ. Buccal drug absorption-II. In vitro diffusion across the hamster cheek pouch. J Pharm Sci 1989; 78: 160-164.

Chettu DJ, Chen LL, Chien YW. Characterization of captopril sublingual permeation: determination of routes and mechanisms. J Pharm Sci 2001; 90: 1868-1877.

Ishizawa T, Hayashi M, Awazu S. Paracellular and transcellular permeabilities of fosfomycin across small intestinal membrane of rat and rabbit by voltage-clamp method. J Pharmacobiodyn 1991; 14: 583-589.

Toropainen E, Ranta V, Vellonen K, Palmgren J, Tavitie A, Laavola M, Suhonen P, Hamalanen KM, Auriola S, Urtti A. Paracellular and passive transcellular permeability in immortalized human corneal epithelial cell culture model. Eur J Pharm Sci 2003; 20: 99-106.

Zhang H, Robinson JR. In Vitro Methods for Measuring Permeability of the Oral Mucosa, in Swarbrick, J: Boylan, JC, (eds), Oral Mucosal Drug Delivery. 1st ed., Vol 74, Marcel Dekker, INC, New York, NY, pp 85-100, 1996.

Morgan DJ, Paull JD, Richmond BH, Wilsen-Evered E, Ziccone SP. Pharmacokinetics of intravenous and oral salbutamol and its sulfate conjugate. Br J Clin Pharmacol 1986; 22: 587-593.

Sweetman SC. Martindale: The complete drug reference, 33th Edn, 2002, Pub. By Pharmaceutical press, London, 770-773.

Takahashi K, Sakano H, Rytting HJ, Numata N, Kuroda S. Influence of pH on the permeability of p- toluidine and aminopyrine through shed snake skin as a model membrane. Drug Dev Ind Pharm 2001; 27: 159-164.

Hoogstraate AJ, Senel S, Cellander C, Verhoef JC, Junginger HE, Bodde HE. Effects of bile salts on transport routes and routes of FITC-lebelled compounds across porcine buccal epithelium in vitro. J Contr Rel 1996; 40: 211-221.

Tsutsumi K, Obata Y, Nagai T, Loftsson T, Takayama K. Buccal absorption of ergotamine tartrate using the bioadhesive tablet system in guinea pigs. Int J Pharm 2002; 238: 161-170.

Cui Z., Mumper RJ. Buccal transmucosal delivery of calcitonin in rabbits using thin-film composite. Anesth Analg 1992; 74: 937-938.

Jeppson AB, Johanson K, Waldeck B. Steric aspect of agonism and antagonism at beta-adrenoreceptors: experiments with

the enantiomers of terbutaline. Acta Pharmacol Toxicol 1984; 54: 285-291.

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Published

2005-09-20

How to Cite

1.
SUTARIYA V, MASHRU R, SANKALIA M, SANKALIA J. Transbuccal delivery of salbutamol sulphate: In vitro determination of routes of buccal transport. Ars Pharm [Internet]. 2005 Sep. 20 [cited 2024 Jul. 22];46(4):337-52. Available from: https://revistaseug.ugr.es/index.php/ars/article/view/5082

Issue

Vol. 46 No. 4 (2005)

Section

Original Articles

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