Comparative in vivo evaluation of propranolol hydrochloride after oral and transdermal administration in rabbits.
The purpose of this study was the in vivo evaluation of orally and transdermally administered propranolol hydrochloride in rabbits. Transdermal patches of propranolol hydrochloride (PPN) were formulated employing ethyl cellulose and polyvinylpyrrolidone as film formers. The pharmacodynamic (PD) and pharmacokinetic (PK) performance of PPN following transdermal administration was compared with that of oral administration. This study was carried out in a randomized cross-over design in male New Zealand albino rabbits. The PK parameters such as maximum plasma concentration (C(max)), time for peak plasma concentration (t(max)), mean residence time (MRT) and area under the curve (AUC(0-alpha)) were significantly (P<0.01) different following transdermal administration compared to oral administration. The terminal elimination half-life (t(1/2)) of transdermally delivered PPN was found to be similar to that following oral administration. In contrast to oral delivery, a sustained therapeutic activity was observed over a period of 24 h after transdermal administration compared to oral administration. The relative bioavailability of PPN was increased about fivefold to sixfold after transdermal administration as compared to oral delivery. This may be due to the avoidance of first pass effect of PPN. The sustained therapeutic activity was due to the controlled release of drug into systemic circulation following transdermal administration.
Rao
P Rama
PR
Pharmacology Division, Indian Institute of Chemical Technology, Hyderabad, AP, India.
Reddy
M Narender
MN
Ramakrishna
Sistla
S
Diwan
Prakash V
PV
D000279:Administration, Cutaneous; D000284:Administration, Oral; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D018592:Cross-Over Studies; D004337:Drug Carriers; D066298:In Vitro Techniques; D008297:Male; D010539:Permeability; D011108:Polymers; D011433:Propranolol / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D011817:Rabbits; D012867:Skin / Q000378:metabolism; D013997:Time Factors
D000319:Adrenergic beta-Antagonists; D004337:Drug Carriers; D011108:Polymers; D011433:Propranolol