Pharmacokinetic studies of ivermectin: effects of formulation.

Studies are reported which describe the effects of formulation, animal species, and route of administration on the pharmacokinetics of ivermectin. Biological half-life t1/2 increases in the order: swine (0.5 day) less than dogs (1.8 day) less than cattle approximately equal to sheep (2.8 day). Formulation modifications, based upon the solubility properties of the drug, have been directed towards the development of a nonaqueous injectable formulation for cattle and an aqueous vehicle for horses. Bioavailability following subcutaneous injection in cattle can be regulated by control of injection solvent composition: a vehicle composed of a mixed aqueous-organic solvent exhibits pharmacokinetic properties (i.e., Cp, t1/2, AUC, and F) intermediate between those furnished by an aqueous formulation and via a purely nonaqueous solvent. The longer apparent biological half-life from this latter vehicle (t1/2 = 8.3 days) confirms that a slow absorption process dominates the pharmacokinetics in the nonaqueous injectable product to produce an effective controlled-release formulation. These bioavailability results illustrate the increase in the concentration of an organic solvent and a concomitant decrease in surfactant concentration in a micellar aqueous system for prolonged drug delivery via injection.

Facile separation of sulfonamides from their degradates by liquid--liquid extraction.

Regulation of acidity for protonation of the free N4-amine can provide for the selective liquid--liquid extraction isolation of a sulfonamide from its degradation products. This principle is applied for the stability-indicating determination of sulfacetamide in the presence of sulfanilamide, sulfaquinoxaline in feed, and sulfabromomethazine in dosage forms. In solution, sulfabromomethazine can exhibit photodecomposition to sulfamethazine. The mean relative errors of the these methods and the precision, represented by relative standard deviations, are each typically less than 2%.

Difference spectrophotometric determination of p-hydroxybenzoic acid in presence of its esters.

A difference spectrophotometric analytical method was developed for the selective determination of p-hydroxybenzoic acid in the presence of its alkyl esters without prior separation. Based on the spectral shift to a shorter wavelength accompanyint carboxyl dissociation, the procedure measures as little as 2% of this acid in mixtures with the alkyl ester preservatives and has an accuracy of 2% mean relative error over the 0.16-12.0 microgram of p-hydroxybenzoic acid/ml range.