Optimization of release kinetics from sustained-release formulations using model-independent pharmacokinetic simulation

✍ Scribed by Cristina Maderuelo; Aránzazu Zarzuelo; José M. Lanao

• Publisher: John Wiley and Sons
• Year: 2011
• Tongue: English
• Weight: 425 KB
• Volume: 100
• Category: Article
• ISSN: 0022-3549
• DOI: 10.1002/jps.22565

✦ Synopsis

In the present work, a single model-independent approach was developed to optimize the release kinetics of drugs from sustained-release formulations, using stavudine (d4T) as a model drug. This approach is based on the pharmacokinetic simulation of drug plasma levels through a semiparametric approach of the input function and on convolution with an empirical polyexponential unit impulse response function. Input functions were evaluated using different zero-order and first-order release constants. Optimum drug release to obtain a specific pharmacokinetic profile was approached using target model-independent pharmacokinetic parameters such as C max SS , C min SS , t max SS , and peak-trough fluctuations. A Monte Carlo simulation was performed to estimate the fractional attainment of d4T plasma concentrations over therapeutic d4T levels. Zero-order (K 0 = 4 mg/h) and first-order (K 1 = 0.05 h -1 ) release constants were optimal for the formulation of sustained-release d4T tablets, plasma concentrations within the therapeutic range being achieved. ©2011