Buccal iontophoretic delivery of atenolol.HCl employing a new in vitro three-chamber permeation cell.
The present work showed that the iontophoretic approach was feasible to enhance buccal drug delivery. A new in vitro horizontal three-chamber iontophoretic permeation cell has been developed to reflect the in vivo iontophoretic drug delivery more closely, electrodes were positioned on the epithelial side in separate chambers. Iontophoretic delivery of atenolol.HCl across porcine buccal mucosa increased proportional to (a) increased initial donor concentration in the range of 0.027 M to 0.10 M atenolol.HCl, (b) increased "on time" of current on/off ratio valued 50/50, 75/25 and 90/10 resulting in enhancement ratios 19, 58, and 112 respectively, initially applying 0.10 M atenolol.HCl and (c) increased current density valued 0.1, 0.2, 0.3, and 0.4 mA/cm(2) obtaining enhancement ratios 6, 18, 36, and 58 respectively, initially applying 0.10 M atenolol.HCl. Microscopy of hematoxyilin-eosin stained sections of porcine buccal mucosae conducting 8-h passive permeation showed minute morphological alterations whereas 8-h iontophoretic treatment showed disordering of the outer epithelial cell layers, alterations being more pronounced in mucosae from reference chambers than donor chambers. The results demonstrated the feasibility of the iontophoretic approach to enhance and control the rate of buccal drug delivery, hence the usefulness of the new permeation cell.
Jacobsen
J
J
Department of Pharmaceutics, The Royal Danish School of Pharmacy, Universitetsparken 2, DK-2100 Copenhagen Ø, Denmark. jeja@dfh.dk
D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage*; D000818:Animals; D001262:Atenolol / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002610:Cheek; D006863:Hydrogen-Ion Concentration; D007478:Iontophoresis; D009061:Mouth Mucosa / Q000378:metabolism*; D010539:Permeability; D013552:Swine
D000319:Adrenergic beta-Antagonists; D001262:Atenolol