Development and Validation of Pharmacokinetic and Pharmacodynamic models of certain new Formulations

Abstract

This thesis deals with the studies carried out by the writer for the past three years on the Development and validation of pharmacokinetic (PK) and pharmacodynamic (PD) models of certain new formulations . Thesis begins with a brief account of the pharmacokinetic pharmacodynamics model, in vitro dissolutions and estimation of drugs in biological medium. The methods used for the PK-PD model development, validation, the steps involved in bio analytical method development, in vitro dissolution methods and their importance have also been discussed. Thesis deals with the scope and objective of the present investigation. The merits of PK-PD in the development of dosage forms and how PK-PD model development necessitates development of new drugs, bio analytical method development and validation are discussed. The objectives of the present study, namely, to optimize the chromatographic conditions, to develop and validate the methods to estimate the selected drugs in the biological fluids by HPLC, development of in vitro dissolution methods and PK-PD model development have been described. It is concluded that the formulated matrix tablets containing dexibuprofen and losartan potassium are capable of exhibiting sustained release properties, stable and feasible for industrial scale production. Thus they are capable of reducing the dose intake, minimize the blood level oscillations, dose related adverse effects, cost and ultimately improve the patient compliance in the therapeutic management of pain and hypertension. It is also concluded that the present PK/PD studies has demonstrated that pain and blood pressure management were found to be effective in developed SR formulations of dexibuprofen and losartan potassium as compared with marketed immediate release formulations. Further studies involving their suitability for long time application, shelf life determination, bioavailability and clinical investigations in large populations may, however, be necessary to further establish its potential and therapeutic efficacy.