Charanjit Rai Behl

Iontophoretic transport of a homologous series of ionized and nonionized model compounds: influence of hydrophobicity and mechanistic interpretation.

An in vitro study was carried out to elucidate the mechanisms controlling iontophoretic transport. The investigation focused on three areas, including the nature of the permeant (state of ionization and hydrophobicity), skin structures (hair follicle distribution and stratum corneum), and various parameters influencing iontophoresis (current, permeant concentration, and competitive ion effects). The data indicate that iontophoretic-facilitated transport is essentially pore mediated and that the transport of ionized and nonionized molecules may be enhanced through the pore-type pathway. The data presented show that iontophoresis has a detrimental effect on the lipoidal transport pathway and that the transport of more hydrophobic nonionized molecules is decreased compared with passive diffusion. The iontophoretic enhancement values decreased linearly with increasing alkyl chain length of n-alkanols. The iontophoretic permeability coefficients of ionized n-alkanoic acids was shown to decrease with increasing permeant hydrophobicity.

Enteral, Oral, and Rectal Absorption of Ceftriaxone Using Glyceride Enhancers

In vivo models in rodents and primates were used to investigate ways of overcoming the poor oral and rectal absorption of ceftriaxone. The sodium salt of ceftriaxone at 20 mg/kg was formulated in C8-C10 chain length, mono- and diglyceride extracts of coconut oil (Capmul) and administered intraduodenally to adult rats. Peak plasma levels of 17-52 micrograms/ml and bioavailability averaging 38% were attained. Significant plasma levels (42-45 micrograms/ml) were also demonstrated in squirrel monkeys with doses of 20 mg/kg ceftriaxone formulated in Capmul and given by the enteral route. Enteric-coated capsules containing this formulation were also orally administered to squirrel monkeys and gave high plasma levels (10-31 micrograms/ml) between 1 and 6 h following dosing. In rectal absorption studies, ceftriaxone formulated in Capmul as a suspension gave peak blood levels of 62-84 micrograms/ml (average bioavailability 42%) in the rabbit. In the baboon, rectal administration of ceftriaxone formulated with Capmul in a Witepsol H15 suppository gave Cmax levels ranging from 9 to 48 micrograms/ml, depending on the dose of the antibiotic and the drug/enhancer ratio.