Iontophoretic in vivo transdermal delivery of beta-blockers in hairless rats and reduced skin irritation by liposomal formulation.
OBJECTIVE
To demonstrate the in vivo transdermal delivery and establish the comparative pharmacokinetics of five beta-blockers in hairless rat.


METHODS
Intravenous dosing was initially done via jugular cannula. For iontophoretic delivery, current (0.1 mA/cm2) was applied for 2 h through a drug reservoir patch containing the beta-blocker (10 mg/ml). Blood samples were collected and analyzed by stereoselective HPLC assays. Any irritation resulting from patch application was quantified by a chromameter. Multilamellar liposomal formulation was prepared by the thin-film hydration method and converted to unilamellar liposomes by extrusion.


RESULTS
With transdermal iontophoresis, therapeutically relevant amounts of propranolol (83.78 +/- 7.4 ng/ml) were delivered within an hour and lasted for up to 4 h. Cmax (185.1 +/- 56.8 ng/ml) was reached at hour 3. A significantly higher amount (p < 0.05) of sotalol HCl was delivered compared to other beta-blockers. There was no significant difference in the S/R ratio of AUC0-t for enantiomers after both intravenous and transdermal delivery. Skin irritation was significantly reduced (p < 0.05) when a liposomal formulation of the propranolol base was used rather than the base itself.


CONCLUSIONS
The comparative pharmacokinetics of intravenous and transdermal iontophoretic delivery of five beta-blockers in hairless rats was established. It was shown that there is no stereoselective permeation.
Department of Pharmaceutical Sciences, School of Pharmacy, Mercer University, Atlanta, Georgia 30341-4155, USA.
Rajkumar
R
Conjeevaram
Ayyappa
A
Chaturvedula
Guru V
GV
Betageri
Gangadhar
G
Sunkara
Ajay K
AK
Banga
D000279:Administration, Cutaneous; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D000818:Animals; D001692:Biological Transport; D002851:Chromatography, High Pressure Liquid; D004337:Drug Carriers; D007275:Injections, Intravenous; D007478:Iontophoresis; D007509:Irritants / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D008081:Liposomes; D008790:Metoprolol / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D010096:Oxprenolol / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D011433:Propranolol / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D051381:Rats; D012867:Skin / Q000187:drug effects* / Q000378:metabolism; D012869:Skin Absorption / Q000187:drug effects; D013015:Sotalol / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D013237:Stereoisomerism; D013999:Timolol / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics
D000319:Adrenergic beta-Antagonists; D004337:Drug Carriers; D007509:Irritants; D008081:Liposomes; D010096:Oxprenolol; D013999:Timolol; D011433:Propranolol; D013015:Sotalol; D008790:Metoprolol