Effect of alcohols and enhancers on permeation enhancement of ketorolac
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Abstract
rate-limiting step for delivery of most of the drugs. Studies were carried out to investigate the effect of pH, alcohols,
and chemical permeation enhancers on the in vitro permeation of ketorolac. The reservoir core of the transdermal patch
was filled with the hydrogel of a nonionic polymer, methocel K15M (hydroxyl propyl methylcellulose, HPMC) formulated
at an optimized pH of 5.4. Enhanced in vitro permeation was achieved after the incorporation of the alcohols. Higher
enhancement was produced by short-chain alcohols like ethanol and isopropyl alcohol (IPA). Propylene glycol (PG) along
with other alcohols, viz. n-propanol, n-butanol, and n-pentanol, lagged behind. An exponential rise in permeation was
observed in flux with an increase in the concentration of IPA. At 25% w/w IPA concentration, the observed ketorolac
flux was 18.04 mg/cm2/h. Terpene containing eucalyptus oil was studied to determine its permeation enhancement
capability. The increase in the concentration of eucalyptus oil enhanced the drug permeation and a maximum flux of
66.38 and 90.56 mg/cm2/h was achieved at 10 and 15% w/w concentrations. The anti-inflammatory potential of the
transdermal formulation was evaluated on a carrageenan-induced paw edema model, with 41.67% inhibition at 6 h.
The skin irritation potential was evaluated by the Drazie test and the formulations prepared were found to be safe. The
reservoir-type transdermal patch for the delivery of ketorolac appeared to be feasible for delivering ketorolac across
the skin.
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References
Buckley MM, Brogden RN. Ketorolac: A review of its pharmacodynamic
and pharmacokinetic properties, and therapeutic potential. Drug
;39:86-109.
Rooks W, Maloney P, Shott L, Schuler M, Sevelius H, Strosberg A,
et al. The analgesic and anti-inflammatory profile of ketorolac and its
tromethamine salt. Drugs Exp Clin Res 1985;11:479-92.
Tiwari SB, Udupa N. Investigation into the potential of iontophoresis
facilitated delivery of ketorolac. Int J Pharm 2003;260:93-103.
Roy SD, Manoukian E, Combs D. Absorption of transdermally delivered
ketorolac acid in humans. J Pharm Sci 1995;84:49-52.
Cho YA and Gwak HS, Transdermal delivery of ketorolac tromethamine:
Effects of vehicles and penetration enhancers. Drug Dev Ind Pharm
;30:557-64.
Tiwari SB, Pai RM, Udupa N. Influence of ultrasound on the
percutaneous absorption of ketorolac tromethamine in vitro across rat
skin. Drug Deliv 2000;11:447-51.
Chavez R, Bravo C, Zazueta C, Pichardo J, Uribe A, Corona N, et al.
Ionophoretic-like properties of ketorolac for calcium. J Pharmacol Exp
Ther 1993;267:1134-9.
Kim BY, Doh HJ, Le TN, Cho WJ, Yong CS, Choi HG, Ketorolac amide
prodrugs for transdermal delivery: Stability and in vitro rat skin
permeation studies. Int J Pharm 2005;293:193-202.
Doh HJ, Cho WJ, Yong CS, Choi HG, Kim JS, Lee CH, et al. Synthesis
and evaluation of Ketorolac ester prodrugs for transdermal delivery.
J Pharm Sci 2003;92:1008-17.
Drazie J. Appraisal of the safety and chemical in foods, drugs and
cosmetics, by the Staff of the Division of Pharmacology, Food and Drug
Administration, Department of Health Education and Welfare. FDA
Officials of U.S. Business Office, Topeka, KS, 1959, 46.
Alol A, Kuriyama K, Shimizu T, Yoshioka M. Effects of vitamin E and
squalene of skin irritation of a transdermal absorption enhancer lauryl
sarcosine. Int J Pharm 1993;93:1-6.
Santoyo S, Arellano A, Ygartua P, Martin C. Penetration enhancer effects
on the in-vitro percutaneous absorption of piroxicam through rat skin.
Int J Pharm 1995;117:219-24.
Megrab NA, Williams AC, Barry BW. Oestradiol permeation across
human skin, silastic and snake skin membranes: The effects of ethanol/
water co-solvent systems. Int J Pharm 1995;116:101-12.
Morimoto H, Wada Y, Seki T and Sugibayashi K, In vitro skin permeation
of morphine hydrochloride during the finite application of penetrationenhancing
system containing water, ethanol and L-menthol. Biol Pharm
Bull 2002;25:134-6.
Williams AC, Barry BW. The enhancement index concept applied to
terpene penetration enhancers for human skin and model lipophilic(oestradiol) and hydrophilic (5-fluorouracil) drugs. Int J Pharm
;74:157-68.
Williams AC, Barry BW. Essential oils as novel human skin penetration
enhancers. Int J Pharm 1989;57:R7-9.
Okabe H, Takayama K, Ogura A, Nagai T. Effect of limonene and related
compounds on the percutaneous absorption of indomethacin. Drug
Des Deliv 1989;4:313-21.
Cornwell PA, Barry BW. Sesquiterpene components of volatile oils as
skin penetration enhancers for the hydrophilic permeant 5-fluorouracil.
J Pharm Pharmacol 1994;46:261-9.
Cornwell PA, Barry BW, Bouwstra JA, Gooris GS. Modes of action of
terpene penetration enhancers in human skin, differential scanning
calorimetry, small-angle X-ray diffraction and enhancer uptake studies.
Int J Pharm 1996;27:9-26.