Evaluation of the effect of different fatty acids on the percutaneous absorption of metaproterenol sulfate.

The in vitro permeation rates of metaproterenol sulfate (MPS) across hairless mouse skin and TESTSKIN living skin equivalent were very low unless skin permeation enhancers were included in the vehicle. An optimum balance should be established between the chain length of the fatty acid and its molar ratio to MPS in order to enhance its penetration through the skin. Thus, the best flux values were shown by capric acid: MPS, 3:1 molar ratio, and lauric acid:MPS, 1:1 and 2:1 molar ratio, while myristic acid:MPS, 1:1 molar ratio, was the optimum under the experimental conditions used. The mechanism of the enhancing effect was examined by measuring 1H NMR spectra and the apparent partition coefficient of MPS, lauric acid, and the mixture. The apparent partition coefficient of MPS between n-octanol and water was higher for the mixture with lauric acid than for MPS alone. A 1:1 molar ratio formulation of MPS and lauric acid was selected for the in vivo permeation study. The data indicated that lauric acid increased the diffusivity of MPS in the skin by forming a complex and by affecting its partition coefficient between the skin and the delivery system.

Comparative in vitro diffusion studies for atenolol transdermal delivery system.

The purpose of this study was to screen atenolol as a candidate for transdermal drug delivery, and to study the release of atenolol from various gels. The percent atenolol release over time profiles indicates that for all the gelling agents used the amount of atenolol released is decreased by increasing the polymer concentration in the gel. The amount of atenolol released was found to be higher from Klucel gels, compared to Methocel and Carbopol gels, with Carbopol gels giving the least release. In studying the effect of atenolol concentration in the gel, it was observed that the amount of atenolol released was increased by increasing the drug concentration in the donor up to a limit corresponding to an atenolol concentration of approximately 2%. This seems to resemble the saturation solubility of atenolol into the gels. Hairless mouse skin and TESTSKIN LSE were used as in vitro skin models.

Monitoring the effect of triamterene and hydrochlorothiazide on dihydrofolate reductase activity using a new spectrophotometric method.

A new spectrophotometric method is developed and applied for the study of the inhibitory effect of triamterene, hydrochlorothiazide and their combinations on the in vitro activity of dihydrofolate reductase enzyme. The method is based on incubating the drug (0.1-1.0 microM) or a buffer control with a solution containing reduced nicotinamide adenine dinucleotide phosphate (0.5 mM), magnesium chloride (1.29 mM), and folic acid as a substrate (0.01-0.1 mM) with the dihydrofolate reductase (0.25 unit). The resulting tetrahydrofolic acid is determined by first hydrolysing it by a methanol-hydrochloric acid mixture to produce p-aminobenzoyl glutamic acid, then adding p-dimethylaminocinnamic aldehyde reagent to form a stable pink coloured product. The colour is found to develop within 5 min and is stable over 12 h, with a maximum absorption at 545 nm. A linear calibration curve is formed by using standard solutions of tetrahydrofolic acid. The presence of the studied drugs did not interfere with the determination. Lineweaver-Burk plots of the reaction kinetics, in the presence of triamterene and/or hydrochlorothiazide showed a competitive inhibition of the dihydrofolate reductase in the presence of triamterene with or without hydrochlorothiazide. A 100% inhibition is obtained by 1 microM solution of triamterene at a folic acid concentration of 0.01 mM. No measurable effect of hydrochlorothiazide at the studied concentration range is demonstrated.