PREPARED BY:- GUIDE BY:- PATEL PARTH Mr. V.M.PATEL M.PHARM SEM-1

DEPARTMENT OF QUALITY ASSURANCEA.P.M.C COLLEGE OF PHARMACEUTICAL SCIENCE &

RESEARCH,HIMMATNAGAR.

APPLICATION OF PHARMACOKINETICS IN NEW DRUG DEVELOPMENT AND DESIGNING OF NOVEL DRUG DELIVERY SYSTEMS.

Design and development of new drugs with greatly improved therapeutic effectiveness and fewer or no toxic effects

Design and development of an optimum formulation for better use of the drug

Design and development of controlled/targeted release formulation

Select the appropriate route for drug administration

Principles

Select the right drug for a particular illness

Predict and explain drug-food and drug-drug interactions  Design an appropriate multiple dosage regimen  Therapeutic drug monitoring in individual patients  Dosage adjustments in situations of altered physiology

and drug interactions

To understand process of absorption, distribution and elimination of drug , which affects onset and intensity of biological response.

To access plasma drug concentration response to given dose which is now considered as more appropriate parameter then intrinsic pharmacological activity .

In design and utilization of in vitro model system that can evaluate dissolution characteristics of new compound formulated as new drug formulations and establish meaningful in vivo in vitro correlation ship.

In design and development of new drug and their appropriate dosage regimen.

In safe and effective management of patients by improving drug therapy.

Applications of pharmacokinetics in NDDS

To understand concept of bioavailability which has been used to evaluate and monitor in vivo performance of new dosage forms and generic formulations.

To carry out bioavailability and bioequivalence studies. We can use pharmacokinetic principles in the development of

various NDDS. e.g. The drug with short half life about 2-6 h can be formulated as controlled release drugs by using polymers . The lower

bioavailability of the drugs can be increased by using several components like β – cyclodextrin List of drug carriers in NDDS :-

Nanosomes, Liposomes, Niosomes, Proniosomes, vesicular drug delivery system, Cubisomes, Aquasomes,

Pharmacosomes,Nanoparticle, Nanosphere, Microsphere, Microparticle, Transferosomes, Micro emulsion, Nanosuspension, Dendrimers, Micelles, Dendrosomes.

Many drugs are investigated now a days and the estimation of their activity and pharmacokinetics properties are important for knowing the ADME of that particular drug . By understanding the mechanism of disease the drug design is done .The drug design is based on the mechanism of the particular disease. Some newly discovered drugs that shows very high activity in in vitro but in in vivo that drug not shows high activity or show high toxic activity. This toxic nature of the drug in in vivo can be explained by studying the pharmacokinetics properties that is the formation of reactive metabolites.

Some newly invented drugs showing undesirable pk properties such as too long or too short t 1/2 , poor absorption and extensive first pass metabolism .

Application of pharmacokinetics in designing of dosage forms

Two physicochemical factors that effect the both extent and rate of absorption are lipophilicity and solubility .

Increase in the lipophilic nature of drug results in increased in oral absorption .

e.g. Biophosphonates drug with poor lipophilicity will be poorly absorbed after oral administration . Absorption of the barbiturates compounds increased with increasing lipophilicity. Higher the lipophilicity of a drug the higher its permeability

and the greater its metabolic clearance due to first pass effect.

Absorption

Solubility is also an important determinant in drug absorption.e.g. HIV protease inhibitors are basically lipophilic and poorly soluble resulting in poor bioavailability. The solubility of

the HIV protease inhibitors can increased by incorporating a basic amine in to the back bone of this series. Pro drugs are developed to improve oral absorption .

e.g. Pivampicillin, Becampicillin are the pro drugs of Ampicillin.

Lipophilicity of the drug affects the distribution. Higher the lipophilicity of a drug the stronger its binding to protein & the greater its distribution.

e.g. Thiopental & polychlorinated insecticides. These drugs are highly distributed and accumulate in adipose

tissue.

Distribution

Determination of metabolic pathways Study of drug metabolic pathways are useful for determining

the nature of metabolites and used for toxicity studies. Isolation & cultured hepatocytes are also often used as in-vitro

models for identifying metabolic pathways of drug.e.g. The major metabolic pathways of indinavir in human

have been identified as, o Glucaronidation at the pyridine nitrogen to yield a quaternary

ammonium conjugateo Pyridine n-oxidationo Para –hydroxylation of the phenyl methyl groupo 3-hydroxylation of the chaino N- depyridomethylation

Drug metabolism

Administration of a drug with a short half life requires frequent dosing and often results in patient incompliance. Half life determined by distribution & elimination. The prolongation of half life can be achieved by increasing the volume of distribution & decreasing the clearance. Latter appear to be easier i.e. to modify the chemical structure to slow down a drug clearance than to increase its volume of distribution.

e.g. The addition of an alkyl amine side chain linked to the dihydropyridine 2-methyl group yield amlodipine with a lower clearance which has an improved oral bioavailability and plasma half life without loss of antihypertensive activity.

Plasma half-life

Biopharmaceutics & clinical pharmacokinetics by Milo Gilbaldi 4th edition , Philadelphia lea & Febiger 1991

Biopharmaceutics & pharmacokinetics a treatise D.M. Brahmankar & Sunil b. Jaiswal ,Vallabh Prakashan Pitampura, Delhi

Text book of Biopharmaceutics & pharmacokinetics by Dr.shobha rani R.Hiremath, prism books Pvt Ltd,bangalore,2002

REFERENCES