Calculation of the dimensions of dosage forms with release controlled by diffusion for in vivo use.
Using numerical models and data obtained from in vitro experiments, the dimensions of diffusion controlled release dosage forms to achieve desired in vivo levels are predicted. Monolithic polymer-drug devices are considered, the release of the drug being controlled by transient diffusion with constant diffusivity. The dimensions of the devices are calculated for various shapes (e.g. spheres, parallelepipeds, cylinders), so that 85% of the drug is released within 6 or 24 h, respectively. Caffeine, diltiazem HCl, and theophylline are studied in ethylcellulose (EC), plasticized with dibutyl sebacate (DBS) or acetyltributyl citrate (ATBC), respectively. The dosage forms are to be administered orally once a day. The resulting drug levels in the plasma are calculated using a numerical model that takes into account: the kinetics of drug release and the pharmacokinetic data of these dosage forms and drugs. Plasma levels resulting from immediate release dosage forms are also calculated, serving as reference.
Ainaoui
A
A
Faculty of Sciences, University of Saint-Etienne, Saint-Etienne, France.
Siepmann
J
J
Bodmeier
R
R
Vergnaud
J M
JM
D000284:Administration, Oral; D002110:Caffeine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D004058:Diffusion; D004334:Drug Administration Schedule; D004337:Drug Carriers; D006801:Humans; D008956:Models, Chemical; D013806:Theophylline / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D014018:Tissue Distribution; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics
D000697:Central Nervous System Stimulants; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D014665:Vasodilator Agents; D002110:Caffeine; D013806:Theophylline