Crosslinked poly(methyl vinyl ether-co-maleic anhydride) as topical vehicles for hydrophilic and lipophilic drugs.

Poly(methyl vinyl ether-co-maleic anhydride) crosslinked with ethylene glycol (GZ-ET), 1,4-butanediol (GZ-BUT), 1,6-exandiol (GZ-EX), 1,8-octanediol (GZ-OCT), 1,10-decanediol (GZ-DEC) or 1,12-dodecanediol (GZ-DOD) was prepared and employed as a supporting material for aqueous topical gels containing pyridoxine hydrochloride (PYCL) chosen as a hydrophilic model molecule or for O/A emulsion containing beta-carotene chosen as a hydrophobic model molecule. We analyzed the effect of the nature of the crosslinker on the permeation of hydrophilic and lipophilic vitamins through porcine skin by in vitro permeation studies. The vehicles formed by crosslinked poly(methyl vinyl ether-co-maleic anhydride) showed enhanced vitamins permeation with respect to the same vehicles formed by noncrosslinked poly(methyl vinyl ether-co-maleic anhydride) (GZ). The decrease in the crosslinker acyl chain length provides vehicles accelerating the drug permeability through the skin.

Validation of a spectrophotometric method for the determination of iron (III) impurities in dosage forms.

A spectrophotometric method (lambda=535 nm) for the iron (III) impurities determination in iron protein-succinylate complex syrup using thioglycolic acid in basic ambient was proposed and validated. Assay samples were treated with 0.1 N hydrochloric acid and centrifuged to remove the interfering active drug. Linear response (r=0.9999) was observed over the range of 0.005-0.2% of the iron (III) with respect to the complex nominal concentration. The accuracy could be considered very satisfactory (recovery=97-99%). The intra-day precision (RSD) of impurity amongst six independent sample preparations, was 1.4%, and there was no significant difference between intra- and inter-day studies. Intermediate precision indicated that the assay possessed high degrees of ruggedness. The limit of quantitation was 0.005% of impurity with respect to the active drug. The results obtained for iron (III) were compared statistically with those obtained with the standard addition method by means of the Student's t-test and the variance ratio F-test; no significative difference was found.

HPLC-fluorescence determination of unconjugated estrogens in pharmaceuticals.

A fluorimetric liquid chromatographic method (lambda(ex) = 280 nm; lambda(em) = 312 nm) was developed for measurements of unconjugated estrogens (estradiol and estriol) in pharmaceutical dosage forms using a reversed-phase column with water acetonitrile at different composition as mobile phase. The in vitro release profiles of three different estradiol transdermal therapeutic systems were determined through a medical-grade silicone rubber subdermal implant material membrane, using a modified Franz diffusion apparatus at 37 degrees C in presence of PEG 400. The HPLC method possesses advantages of rapidity, simplicity and accuracy.

HPLC determination of glutathione and L-cysteine in pharmaceuticals after derivatization with ethacrynic acid.

Ethacrynic acid and its methyl ester are proposed as useful pre-chromatographic derivatization reagents for the HPLC analysis (UV detection) of reduced glutathione (GSH) and L-cysteine. The optimum experimental conditions for the thiol derivatization, the removal of the excess reagent by liquid-liquid or solid-phase extraction and the reversed-phase chromatographic separations of the thiol adducts were investigated. The method was applied to the HPLC determination of GSH and L-cysteine in commercial formulations and proved to be suitable for the HPLC determination of oxidized glutathione (GSSG) after reduction to GSH using dithiothreitol (DTT).

Determination of ethacrynic acid in pharmaceutical formulations by difference ultraviolet spectrophotometry after derivatisation with N-acetylcysteine.

A selective difference spectrophotometric procedure is described for the assay of ethacrynic acid (a diuretic drug) in pharmaceutical dosage forms. The method is based on the reaction of the drug with N-acetylcysteine at pH 7.4 and ambient temperature, affording thiol adducts having different spectral properties, and involves the measurement of the absorbance of the reaction mixture relative to an equimolar solution of unreacted ethacrynic acid. The absorbance at 270 nm (A(270)) and the absorbance difference, delta A=A(270-A(244), obtained from the difference spectrum, were found to be linearly correlated with the drug concentration. The proposed spectrophotometric procedure was applied successfully to the determination of ethacrynic acid in pharmaceutical formulations using a reversed-phase high-performance liquid chromatographic procedure as a reference method.

Colorimetric determination of acetylcysteine, penicillamine, and mercaptopropionylglycine in pharmaceutical dosage forms.

A colorimetric determination of acetylcysteine, penicillamine, and mercaptopropionylglycine is described. The method is based on the oxidation of mercapto-compounds with iron(III) in the presence of 1,10-phenanthroline. The iron(II) formed was quantitatively and rapidly converted to the stable tris(1,10-phenanthroline)iron(II) complex measured spectrophotometrically at 515 nm. The results obtained from various commercial formulations indicate that the method proposed allows a simple, sensitive determination of these mercapto-drugs with good accuracy (99.5-101% recovery) and remarkable precision (RSD +/- 0.6-1.6%).