Question

How half life influence design of controlled drug delivery system?

Answer 1

Answer:

Design of controlled release delivery systems using a modified pharmacokinetic approach: a case study for drugs having a short elimination half-life and a narrow therapeutic index

International Journal of Pharmaceutics

Volume 261, Issues 1–2, 11 August 2003, Pages 27-41

Design of controlled release delivery systems using a modified pharmacokinetic approach: a case study for drugs having a short elimination half-life and a narrow therapeutic index

The objectives of peroral controlled release drug delivery systems (CRDDS) are to maintain therapeutically effective plasma drug concentration levels for a longer duration thereby reducing the dosing frequency and to minimise the plasma drug concentration fluctuations at steady state by delivering drug in a controlled and a reproducible manner. Drug delivery rate, duration of delivery and the dosing interval are the target features for any temporal CRDDS. The classical pharmacokinetic model for designing CRDDS [Drug Dev. Ind. Pharm. 15 (1989) 1073] assumes the time of drug delivery (tdel) to be less than the dosing interval. However, termination of drug release from such a CRDDS at tdel and/or a declining drug input function towards the terminal phase of tdel from a first order kinetic CRDDS can have severe implications on plasma drug concentration and steady state fluctuations for a drug with very short half-life. A case study is presented in this paper, wherein by means of theoretical calculations using a classical pharmacokinetic approach, it is shown that a first order kinetic CRDDS for hypothetical drugs with short elimination half-life and different pharmacokinetic conditions would result in sub-therapeutic plasma concentrations at least for some time during the dosing interval at steady state. In order to avoid sub-therapeutic plasma drug concentrations a modification in classical pharmacokinetic model is proposed and discussed through theoretical calculations for different hypothetical pharmacokinetic situations