Transdermal drug delivery systems of albuterol: in vitro and in vivo studies.

In vitro and in vivo experiments were conducted with double- and single-layer albuterol transdermal pads designed for once-a-day application. In the in vitro experiments, dissolution of albuterol from pads and permeation of albuterol through hairless mouse skin were monitored. In the in vivo experiments, pads were applied to the chest area of four female rhesus monkeys (Macaca mulata), and an albuterol aqueous solution was injected into the saphenous vein of the same animals in a crossover design. The amount lost from pads applied to monkeys was monitored by analysis of pad residue. Blood samples were withdrawn at regular intervals and analyzed by a high-performance liquid chromatography-fluorescence method. Skin irritation due to the pad was measured by a modified Draize score test. The amounts released from the two formulations were similar. The amount released was, however, dependent on the technique used and decreased in the following manner: pad dissolution greater than in vivo amount lost from pads applied to monkeys greater than in vitro permeation through hairless mouse skin. The pharmacokinetic parameters determined after intravenous and transdermal administration were as follows: terminal half-life, 2.26 +/- 0.45 h; apparent volume of distribution, 1935 +/- 37.2 mL.kg-1; and total body clearance, 612.0 +/- 118 mL.h-1.kg-1. The average concentrations in serum after application of single- and double-layer pads were 44.60 +/- 16.40 and 62.50 +/- 8.00 ng/mL, respectively. Further, the amount lost from pads applied to monkeys correlated with the respective amount absorbed in monkeys, as calculated from the average concentration in serum and clearance.(ABSTRACT TRUNCATED AT 250 WORDS)

Drug release from methyl acrylate-methyl methacrylate copolymer matrix III: stimultaneous release of noninteracting drug-excipient mixtures.

The simultaneous release of mixtures of noninteracting chemicals incorporated in a methyl acrylate-methyl methacrylate copolymer was studied. Different mixtures of dextrose-methapyrilene hydrochloride and sodium chloride-methapyrilene hydrochlodire in the plastic were compressed into tablets, and single-surface release was obtained in 0.N HCI at 37 degrees. The amounts of both drug and excipients released per unit surface rate constants were analysed in terms of the solubility, diffusion coefficient, concentrations of each chemical, and porosity and tortuosity of the tablets. It was concluded that for each tablet system the individual solid-liquid boundaries of the incorporated chemicals had merged together, and the release could be explained by Higuchi's square foot of time relationship.