Biopharmaceutic and pharmacokinetic aspects in the design of controlled release peroral drug delivery systems

Abstract

Present peroral controlled release drug delivery systems (CRDDS) are for a maximum of 24 hours clinical effectiveness. Such systems are primarily for drugs of short elimination half-life. However, also drugs of long half-life qualify if a reduction in steady state fluctuation is desired. The biopharmaceutic evaluation of a drug for potential use in CRDDS requires knowledge on the absorption mechanism of the drug from the G. I. tract, the general absorbability, the drug's molecular weight, pKa, solubility at different pH and apparent partition coefficient. The pharmacokinetic evaluation requires knowledge on a drug's elimination half-life, total clearance, absolute bioavailability, possible first-pass effect, and the desired steady concentrations for peak and trough. Even if a drug's disposition after I. V and peroral fast release administration is best described by a two-or higher-compartment model, one can collapse these for all practical purposes to a one-compartment model for the design of a CRDDS if the release rate is much smaller than the intrinsic absorption rate and the distribution rates, and is the actual rate-limiting process. Two simple approaches for the pharmacokinetic design of required release characteristics and required maintenance dose to achieve desired steady state maximum and minimum concentrations are discussed, one for zero-order and one for first-order release.