Viscosity of pharmacopeial multimolecular ointment vehicles and pharmaceutical availability of a model therapeutic agent.

Viscosity was tested of basic ointment vehicles such as: white petrolatum, yellow petrolatum, anhydrous lanolin and eucerin produced by different manufacturers. Ointment vehicles of definite type differ significantly in rheological parameters. In the same group of products, the experimentally determined viscosity value of some vehicles is two-fold (petrolatum, anhydrous lanolin) or even three-fold (eucerin) higher than that of others. On the basis of rheological tests, using Einstein-Smoluchowski equation (D = kT/ 6pireta), theoretical coefficient was calculated of a model therapeutic agent--salicylic acid diffusion (-log chi2(i) = 1,22) from the tested vehicles to the external compartment. The obtained results were related to the performed in vitro measurements of the rate of salicylic acid release from the above mentioned ointment vehicles to model acceptor fluid. High correlation was observed between theoretical values of diffusion coefficients calculated on the basis of viscosity measurements and tested experimentally pharmaceutical availability of salicylic acid. It was confirmed by describing this dependence with regression equations of high correlation coefficients (r > or = 0,9667). Marked disproportions between rheological parameters of the vehicles of definite type produced by individual manufacturers are the cause of differences in pharmaceutical availability of therapeutic agents contained in these vehicles.

Measurement of salicylic acid in human serum using stable isotope dilution and gas chromatography-mass spectrometry.

A simple, highly selective, and sensitive method using stable isotope dilution and gas chromatography-mass spectrometry has been developed to quantify salicylic acid (SA) at concentrations naturally occurring in biological fluids, such as in the serum of subjects not taking aspirin. After extraction of liquid-liquid with diethyl ether and ethyl acetate and preparation of the tert-butyldimethylsilyl derivative, SA content was detected using deuterated SA as internal standard. The mean recovery of SA from serum was 85 +/- 6%. Intra- and interday precision and % relative error were <15% in all cases. With a detection limit of 0.6 ng and a quantification limit of 2 ng, the method is therefore also adequate for population studies because of the small amount of blood necessary to perform the analyses.

Performance of USP calibrator tablets in flow-through cell apparatus.

USP dissolution calibrator tablets were analysed by the flow-through cell method with the intention of examining its applicability for the flow-through cell apparatus suitability test. Test was performed with Dissotest CE-6 apparatus, (Sotax, Switzerland) in flow-through cells for tablets and capsules: smaller cells of 12 mm diameter and larger ones of 22.6 mm diameter. Analyses were performed with laminar and turbulent flow of dissolution medium. The flow rates were 16 and 8 ml/min for laminar flow and only 16 ml/min for turbulent flow. From the results it can be concluded that both salicylic acid tablets and prednisone tablets could be used for apparatus suitability test also for the flow-through cell under the conditions of laminar flows of 16 and 8 ml/min in cells phi 12 and 22.6 mm. As regards the turbulent flow of 16 ml/min, without a holder, cells phi 12 mm could be used for salicylic acid tablets and both cells (phi 12 and 22.6 mm) for prednisone tablets.

Limitation of the Vitros dry-slide technique in measuring high concentrations of salicylate in plasma.

The linearity of the Vitros dry-slide method for plasma salicylate was assessed in two ways: serial concentrations of sodium salicylate were added to fresh lithium heparin plasma, and the salicylate was determined both neat and in dilution. Vitros salicylate results submitted to the Heathcontrol External Quality Assessment Scheme were compared to the spike value. Similar loss of linearity was observed in both cases. Serious salicylate overdosage requiring specific clinical treatment may have been underestimated.