Paul Ashton

Surfactant effects in percutaneous absorption I. Effects on the transdermal flux of methyl nicotinate

Abstract We have investigated the effects of a series of surfactants on the permeability of human skin in vitro using methyl nicotinate as a model drug. The surfactants used were cetyl trimethyl ammonium bromide, sodium lauryl sulphate, decyl methyl sulphoxide and Brij 36T. These surfactants have a linear alkyl chain of 10–12 units linked to different hydrophilic groups. We found that while the ionic surfactant exerted a greater effect on the flux of methyl nicotinate, the nonionic surfactants had a smaller but more immediate effect on the flux. This is consistent with the hypothesis that for compounds to disturb the permeability barrier of the stratum corneum they must first penetrate it themselves. Ionic compounds can be expected to penetrate this lipophilic barrier more slowly than nonionic compounds of a similar structure and therefore will take longer to elicit their effects.

Clearance and distribution of ciprofloxacin after intravitreal injection.

This study was designed to determine the drug concentration and clearance after intravitreal injection of ciprofloxacin. Ciprofloxacin (100 micrograms/0.1 cc) was injected into the vitreous of normal eyes and into eyes that had undergone lensectomy and vitrectomy. Drug concentration was determined using high-pressure liquid chromatography analysis 0.5, 2, 4, and 12 hours after injection. In normal eyes, the elimination half life was 2.2 hours with a distribution volume of 1.2 ml. In aphakic vitrectomized eyes, the half life was 1 hour and the distribution volume was 1.4 ml. The majority of the drug appears to leave via a transretinal route, but clearance was not inhibited by probenecid. Because of the relatively short half life, intravitreal administration of ciprofloxacin for the treatment of endophthalmitis would provide only short-term therapy and would need to be supplemented by other forms of treatment.

Surfactant effects in percutaneous absorption II. Effects on protein and lipid structure of the stratum corneum

Abstract The effects of several known penetration enhancers on the lipid structure of human stratum corneum have been investigated by differential scanning calorimetry. Effects on the birefringence were also examined. A correlation was found to exist between the ability of a compound to increase the birefringence of the stratum corneum and its reported tendency to induce local irritation when applied to the skin.

Reaction of N-benzoyl amino acids with oxalyl chloride: a facile route to 4-substituted 2-phenyloxazole-5-carboxylates

N-benzoyl amino acids 1a–g react with excess oxalyl chloride at room temperature followed by addition of alcohols to afford 4-substituted 2-phenyloxazole-5-carboxylates 3a–g.