Transdermal iontophoretic delivery of timolol maleate in albino rabbits.
The use of transdermal iontophoresis is a promising technique for the systemic delivery of water soluble and ionic drugs of relatively large molecular size. The present study investigates the skin pre-treatment with Azone (laurocapram) and iontophoresis on the pharmacodynamic effect of timolol maleate (TM) in vivo in albino rabbits. The pharmacodynamic effect of TM was evaluated by transdermal delivery and compared with an intravenous (i.v.) administration. Iontophoresis of TM (0.1 mg/ml) produced a significant inhibition in the isoprenaline (ISP)-induced tachycardia. Iontophoresis with higher concentration of TM (1 mg/ml) produced a 100% inhibition of the ISP induced tachycardia. Pre-treatment of skin with Azone (3% v/v emulsion) eliminated the lag time and prolonged the duration of action of iontophoresis from 4 to 6 h. The AUC of Azone treated group was significantly higher than that of the untreated group (P<0.05). Further, the AUC with iontophoretic delivery and pre-treatment of Azone was comparable to that of intravenous TM (30 microg/kg). In conclusion, iontophoresis in combination with Azone can increase the transdermal delivery of TM, whereby the required transport rate can be achieved with a lower drug concentration.
Kanikkannan
N
N
College of Pharmacy, Florida A & M University, Tallahassee, FL 32307, USA. kanikkannan@hotmail.com
Singh
J
J
Ramarao
P
P
D000279:Administration, Cutaneous; D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D000818:Animals; D019540:Area Under Curve; D001381:Azepines; D004655:Emulsions; D005079:Excipients; D006207:Half-Life; D007275:Injections, Intravenous; D007478:Iontophoresis; D007545:Isoproterenol; D008099:Liver / Q000378:metabolism; D011817:Rabbits; D012996:Solutions; D013610:Tachycardia / Q000139:chemically induced / Q000517:prevention & control; D013999:Timolol / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D001381:Azepines; D004655:Emulsions; D005079:Excipients; D012996:Solutions; C035229:laurocapram; D013999:Timolol; D007545:Isoproterenol