%0 Journal Article
%T Pharmacokinetic-Pharmacodynamic Model of Newly Developed Dexibuprofen Sustained Release Formulations
%A Selvadurai Muralidharan
%J ISRN Pharmaceutics
%D 2012
%R 10.5402/2012/451481
%X Pharmacokinetic-pharmacodynamic (PK-PD) modeling has emerged as a major tool in clinical pharmacology to optimize drug use by designing rational dosage forms and dosage regimes. Quantitative representation of the dose-concentration-response relationship should provide information for the prediction of the level of response to a certain level of drug dose. This paper describes the experimental details of the preformulation study, tablet manufacture, optimization, and bioanalytical methods for the estimation of dexibuprofen in human plasma. The hydrophilic matrix was prepared with xanthen gum with additives Avicel PH 102. The effect of the concentration of the polymer and different filler, on the in vitro drug release, was studied. Various pharmacokinetic parameters including AUC0¨Ct, AUC0¨C¡Þ, , , , and elimination rate constant ( ) were determined from the plasma concentration of both formulations of test (dexibuprofen 300£¿mg) and reference (dexibuprofen 300£¿mg tablets). The merits of PK-PD in the development of dosage forms and how PK-PD model development necessitates the development of new drugs and bio analytical method development and validation are discussed. The objectives of the present study, namely, to develop and validate the methods to estimate the selected drugs in the biological fluids by HPLC, the development of in vitro dissolution methods, and PK-PD model development have been described. 1. Introduction Dexibuprofen, S(+)-ibuprofen, is a pharmacologically active form and is more potent than ibuprofen, which has equal quantities of R(£¿)- and S(+)-enantiomers [1]. Ibuprofen is an NSAID and is widely used to reduce pain, fever, and inflammation. This drug inhibits cyclooxygenases and activates peroxisome proliferators-activated receptors; both of these actions result in reduced inflammation [2¨C4]. Pharmacokinetic-pharmacodynamic (PK-PD) modeling is a scientific tool to help developers selecte a rational dosage regimen for confirmatory clinical testing. PK/PD modeling can be executed using various approaches, such as direct versus indirect response models and parametric versus nonparametric models. PK/PD concepts can be applied to the individual dose optimization. The limits of PK/PD approaches include the development of appropriate models, the validity of surrogate endpoints, and the acceptance of these models in a regulatory environment. PK-PD modeling allows the estimation of PK-PD parameters and the prediction of these derived, clinically relevant parameters as well. PK-PD simulations allow the assessment of the descriptive parameters as
%U http://www.hindawi.com/journals/isrn.pharmaceutics/2012/451481/