No abstract

A new formulation for nasal administration containing 17 beta-estradiol (E2) with dimethyl-beta-cyclodextrin (DM beta C) as a solubilizer and absorption enhancer is described. Nasal administration of this E2-DM beta C formulation gave a significantly higher E2 absorption than an E2 suspension in both rabbits and rats. Relative to an intravenous injection of the E2-DM beta C formulation, absolute bioavailabilities of 94.6 and 67.2% were calculated for the nasal E2-DM beta C formulation in rabbits and rats, respectively. Differences in bioavailability may have resulted from differences in experimental animal conditions. The effects on human nasal ciliary activity of the E2-DM beta C formulation were studied with an in vitro method. The formulation was found to exert only a minor effect on ciliary beat frequency. Thus, nasal delivery of E2, using a cyclodextrin inclusion formulation, may have potential for clinical application, e.g., in the therapy of postmenopausal disorders.

No abstract

Atracurium is a novel his-quaternary (x~mpetitive neuromuscular blocking agent. The drug was designed to undergo lapid chemical inactivation by "Rofmann elimination" at physiological pH and temperature to form laudancsine. Beside hydrolysis, atracurium is metabollzed to a quaternary alcohol and acid and metholaudanosine, which all breakdown to laudanosine. ( I ) It is known that laudanosine can induce oonvulslons. We developed a method for the determination of atracuri~m and laudano6ine in one run: I ml serum, 50 ~I sulphuric acid I M, 0.1 ml internal standard (hexafluorenium bromide I0 mg 1 -I ) and 0.1 ml potassium iodide solution (50 g 1 -j) are mixed; 7.0 ml DCM was added and 50 ~i is injected into the HPLC. Eluens: acetonitrile + sodium sulphate 0.03 M = 25 + 75, + sulphuric acid I M to pa 3.5 ; column 150 x 4.6 ram, Nucleosil 5C18; detection LrV at 210 nm, and fluorescence Em.320 nm, Exc. 280 urn. Sensitivity in spiked calf's serum: atracurium 25 ~g.l -I and lau~anosine 5 ~g.l -I . With this method and with the more time consuming assay of Neill and Jones (2) (unlike their publication), we al~ys found two peaks from the pure su~stanoe atracurium. ~ two did not correspond with the known degradation p rgducts. By TiC we could confirm our findings. In Tracrium~ ampoules (atracurium for h~an i.v. injection) we found with our method atracurium and three degradation pLod.,cts.

No abstract