Muralidharan, S (2010) Development and Validation of Pharmacokinetic (PK) and Pharmacodynamic (PD) Models of Certain New Formulations. Doctoral thesis, The Tamil Nadu Dr. M.G.R. Medical University, Chennai.
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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 pharmacodynamic 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. A review of literature on PK-PD model development available for the drugs in biological fluids is presented. 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. Thesis also deals with the experimental procedures adopted. It describes in detail the procedures adopted for the bioequivalence study design & data handling, optimization and validation of the chromatographic conditions for the estimation of the drugs in plasma and selected sustained release (SR) formulations, PK-PD model development. The results obtained are presented, supported by tables and figures and discussed in detail. The discussions include, • Bioavailability study design and data handling, • Optimization and validation of the chromatographic conditions for the estimation of the drugs in plasma and selected SR formulations are discussed such as, • chromatograms obtained, • accuracy, • reproducibility (intraday and interday variations), • specificity, • linearity and range, • LOD and LOQ, • ruggedness and robustness, • stability and • system suitability studies. • in vitro data analysis • pharmacokinetcc data analysis • pharmacodynamic data analysis and model development The following are some of the salient features of the present study; • A single dose, randomized, complete and two treatments cross over study was conducted in healthy human subjects and plasma concentrations were estimated by a sensitive, validated methods. • The selected drug candidates dexibuprofen and losartan potassium that are predominantly ionized at gastrointestinal pH ranges and are well absorbed after oral administration. • The effect of polymer concentration on the in vitro behavior was significant. In general an increase in the polymer concentration retarded the drug release significantly. • The stability studies of the developed sustained release formulations of dexibuprofen and losartan potassium are stable under accelerated conditions for three months. • The developed HPLC methods for the estimation of dexibuprofen and losartan potassium in plasma are accurate, precise, selective, linear and were used for the bioavailability studies of developed formulations. • The formulated sustained release tablets are capable of exhibiting sustained blood levels as compared to commercially available immediate release tablets. • The comparative bioavailability studies of the developed sustained release tablets and marketed immediate release tablets indicated that the drugs from SR formulations were well absorbed and the extent of absorption was higher than that of the marketed conventional tablets. The sustained and efficient drug delivery developed in the present study will maintain plasma drug levels, better, which will overcome the drawbacks associated with conventional therapy. • The pharmacokinetic parameters of the two different formulations of dexibuprofen and losartan potassium were compared statistically by one way ANOVA (analysis of variance) by SPSS version 13.0. The pharmacokinetic parameters like Tmax, AUC0-t, t½, Kel and AUC0-∞ of the immediate release and sustained release formulations of dexibuprofen and losartan potassium were found to be significantly different (P<0.05) by one way ANOVA. Based on these observations, 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 thee 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.
| Item Type: | Thesis (Doctoral) |
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| Uncontrolled Keywords: | Pharmacokinetic, Pharmacodynamic, Development, Validation, formulations. |
| Subjects: | PHARMACY > Pharmaceutical Analysis |
| Depositing User: | Devi S |
| Date Deposited: | 27 Jun 2017 05:50 |
| Last Modified: | 17 Sep 2022 11:03 |
| URI: | http://repository-tnmgrmu.ac.in/id/eprint/399 |
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