Acta pharmaceutica Nordica最新文献

A number of imidazo[2,1-b]thiazoles bearing a 2,6-dichlorophenyl group as hydrazone or as amide were prepared and tested in rats as antihypertensive agents. Only compounds bearing a chlorine at position 6 were active.

The simplex centroid design was applied to the optimization of a modified release tablet formulation. A base granulation was made with the active ingredient naftidrofuryl. The variables investigated included fractions of the excipients microcrystalline cellulose, lactose and dicalcium phosphate dihydrate. The release rate, crushing strength, friability and weight variation were determined as response parameters. Mathematical models were fitted to the data obtained by the lattice method, described by Scheffé and by means of multiple linear regression. Regression analysis indicated a relatively good fit of the models. On the basis of the regression models, contour plots were constructed. An increase in the amount of dicalcium phosphate caused lower release rate and increased weight variation. An increase in the content of lactose showed lower strength and increased friability, whereas an increase in the amount of microcrystalline cellulose had the opposite effect.

The bioavailability of noscapine base administered in lozenges in a dose of 100 mg to twelve healthy volunteers, in a study using an open balanced cross-over design, was compared with that of 100 mg of noscapine hydrochloride given perorally as a mixture. The bioavailability of noscapine after administration in lozenges was significantly higher than that after administration of the drug as a mixture. It is concluded that the lozenges containing noscapine base may be a valuable alternative to the conventional noscapine hydrochloride mixture.

A quantitative structure-activity relationship (QSAR) for some 6-methoxybenzamides having 1-ethyl-2-pyrrolidinylmethyl side chains with respect to the inhibition of [3H]spiperone binding is established using the PLS method. An experimental design approach to select the training set compounds is demonstrated. The established relationship between structure and in vitro activity indicates the dominating influence of the substituents in the 3-position as well as the importance of (S)-configuration in the side chain. A methoxy substituent in the 5-position is also beneficiary for high activity. Both salicylamides and non-salicylamides could be accommodated in the analysis, which supports the notion of a common binding site in the receptor.

The main alkaloid in the roots of Thalictrum flavum is berberine. The alkaloids glaucine, thalicsimidine, thaliglucine, thalidazine, hernandezine and thalfoetidine were also isolated.

The stability of tauromustine in buffered aqueous solutions was investigated over the pH range 0.9-7.5. The pH rate profile at zero buffer concentration has a specific acid catalytic region at pH below 2, a plateau of pH-independent degradation between pH 2 and 4, and shows a sharp increase in the degradation rate at pH above 4. The activation parameters, the solvent isotope effect and the effect of the dielectric constant on the degradation rate were determined, and possible degradation mechanisms were discussed. The effects of six cyclodextrin (CD) derivatives on the stability of tauromustine in aqueous buffer solutions were investigated. All the CDs tested had some stabilizing effect on the drug at pH 1.98 and 4.06 but they had little or no effect at pH 6.38. Hydroxypropyl-alpha-cyclodextrin (HP alpha CD) had the largest stabilizing effect. Tauromustine degraded about 25 to 50% slower in aqueous buffer solutions containing 2% HP alpha CD compared to buffer solutions containing no CD.