Online citations, reference lists, and bibliographies.
← Back to Search

Enhancement Of The Antiinflammatory Effect Of Ethyl 4-Biphenylyl Acetate In Ointment By β-Cyclodextrin Derivatives: Increased Absorption And Localized Activation Of The Prodrug In Rats

Hidetoshi Arima, H. Adachi, T. Irie, K. Uekama, J. Pitha
Published 2004 · Chemistry, Medicine

Save to my Library
Download PDF
Analyze on Scholarcy
Ethyl 4-biphenylyl acetate (EBA) is a prodrug of the antiinflammatory 4-biphenylyl acetic acid (BPAA). The inclusion complexes of EBA with β-cyclodextrin (β-CyD), heptakis(2,6-di-O-methyl)-β-cyclodextrin (DM-β-CyD), and 2-hydroxypropyl-β-cyclodextrin (HP-β-CyD) at a molar ratio of 1:2 (EBA:cyclodextrin) were prepared and used to make hydrophilic antiinflammatory ointments. The in vitro release of EBA from the ointments was enhanced by complexation in the order of β-CyD < DM-β-CyD ≤ HP-β-CyD. The improvement correlated with the improved solubility and not with the decreased diffusibility observed to occur upon the complexation of EBA. In vivo the complexation with cyclodextrin derivatives increased both the release of EBA from the vehicle and its conversion in the underlying tissue to BPAA, but the total of EBA and BPAA in the tissue was decreased. In vitro studies confirmed that the effects of cyclodextrin derivatives on the conversion were exerted indirectly. The combination of the enhanced release and of the enhanced prodrug hydrolysis by esterases in the site where the antiinflammatory action is required resulted in increased therapeutic effects. In the model of carrageenan-induced acute edema in rat paw, the complexation improved the therapeutic effects over those of EBA alone in the order of β-CyD < DM-β-CyD < HP-β-CyD. HP-β-CyD may be a particularly useful cyclodextrin derivative since it improves the topical availability and does not irritate tissues.
This paper references
Rate of release of medicaments from ointment bases containing drugs in suspension.
T. Higuchi (1961)
Prodrugs for dermal delivery
S. Chan (1989)
Pharmaceutical evaluation of hydroxyalkyl ethers of β-cyclodextrins
A. Yoshida (1988)
Effects of β-cyclodextrin and di-O-methyl-β-cyclodextrin on the percutaneous absorption of butylparaben, indomethacin and sulfanilic acid
H. Okamoto (1986)
Drug solubilizers to aid pharmacologists: amorphous cyclodextrin derivatives.
J. Pitha (1988)
Hydroxypropyl-β-cyclodextrin: preparation and characterization; effects on solubility of drugs
J. Pitha (1986)
Differences in the enhancing effects of water soluble β-cyclodextrins on the release of ethyl 4-biphenylyl acetate, an anti-inflammatory agent from an oleaginous suppository base
Hidetoshi Arima (1989)
Percutaneous absorption and metabolism of hydrocortisone butyrate propionate in dog skin.
Y. Ozawa (1985)
Skin metabolism of topically applied compounds
R. J. Martin (1987)
Analysis of data on the medicament release from ointments.
W. Higuchi (1962)
K. Uekama (1987)
An attempt to reduce the photosensitizing potential of chlorpromazine with the simultaneous use of β- and dimethyl-β-cyclodextrins in guinea pigs
T. Hoshino (2004)

This paper is referenced by
Semantic Scholar Logo Some data provided by SemanticScholar