Pharmacokinetic-Pharmacodynamic Model of Newly Developed Dexibuprofen Sustained Release Formulations

Selvadurai Muralidharan

doi:10.5402/2012/451481

Abstract

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–t, AUC0–∞, C max, T max, T 1/2, and elimination rate constant (K el) 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.

Highlights

Dexibuprofen, S(+)-ibuprofen, is a pharmacologically active form and is more potent than ibuprofen, which has equal quantities of R(−)- and S(+)-enantiomers [1]
This section describes the experimental results obtained in the present investigation in the form of tables and figures along with a detailed analysis on the results of preformulation study, tablet manufacture, bioavailability study design, data handling, optimization and validation of the bio analytical methods for the estimation of dexibuprofen in human plasma samples, amount of the selected drugs present in plasma samples, in vitro dissolution method, determination of pharmacokinetic parameters, statistical evaluation, in vivo and in vitro data analysis, and pharmacodynamic model
The results indicated by the pain scale [29] of the developed dexibuprofen Sustained Release (SR) tablets have shown notable pain relief when compared to the marketed immediate release (IR) tablets

Summary

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]. In the case of PD variability, it becomes important to identify the useful predictor (covariates) of PD individuality to facilitate the individually optimized pharmacotherapy It is necessary, to establish very comprehensive patient profiles during the development of studies. After single doses (nonsteadystate condition) and when time variant PD parameters are present, more complex models are needed to account for phenomena involved in the PK-PD relationship Approaches such as disequilibrium between biophase and plasma compartment [12], the appearance of active metabolites [16, 17], indirect mechanisms of action [18, 19], sensitization, and tolerance [20,21,22] have been proposed to explain the apparent dissociation between time courses of concentration and effect. At present there is no PK/PD studies of the developed formulation have been reported

Reagents and Chemicals Used

Instruments Used

Pharmacodynamic Model for Dexibuprofen

Results and Discussion

Conclusion