Dendrimer-mediated transdermal delivery: enhanced bioavailability of indomethacin.
The transdermal delivery of aqueous formulations of indomethacin, a model drug, with different concentrations of three types of dendrimer showed a linear increase in flux with increasing concentration of each of the dendrimers. This result was in contrast to phase solubility studies, where Higuchi's A(N) profile was observed. The steady-state flux of the drug increased significantly and was highest with the G4-NH2 dendrimer at 0.2% w/v concentration, which showed an enhancement factor of 4.5 compared to the pure drug suspension. In vivo, a steady-state flux was achieved in 5 h, and the C(max) values were significantly higher with G4-NH2 and G4-OH dendrimer formulations. The [AUC](0-24h) of G4-NH2 (2.27 times) and G4-OH (1.95 times) formulations were significantly higher than that of the pure drug, but was only marginally higher in the case of G-4.5 dendrimer formulation. The % inhibition of paw volume showed a trend comparable to the pharmacokinetic data and a maximum of 1.6- and 1.5-fold increase was found with G4-NH2 and G4-OH formulations, respectively, compared to the pure drug suspension.
Chauhan
Abhay S
AS
Pharmacology Division, Indian Institute of Chemical Technology, Uppal Road, Tarnaka, 500-007 Hyderabad, India.
Sridevi
S
S
Chalasani
Kishore B
KB
Jain
Akhlesh K
AK
Jain
Sanjay K
SK
Jain
N K
NK
Diwan
Prakash V
PV
D000279:Administration, Cutaneous; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D007213:Indomethacin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012869:Skin Absorption; D012995:Solubility; D013997:Time Factors
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007213:Indomethacin