Bioavailability ppt

BIOAVAILABILITY

1. BIOAVAILABILITY AND BIOEQIVALENCE A BASIC CONCEPT AYAN PAL M.PHARM, 1 ST SEM DEPARTMENT OF PHARMACEUTICS CALCUTTA INSTITUTE OF PHARMACEUTICAL TECHNOLOGY AND AHS

2. CONTENTS INTRODUCTION DEFINITION OBJECTIVE SIGNIFICATION METHODS OF BIOAVAILABILITY MEASUREMENT BIOEQUIVALANCE EXPERIMENTAL STUDY DESIGN

3. INTRODUCTION   Bioavailability (denoted as F and generally expressed as a percentage, F%) quantifies the proportion of a drug which is absorbed and available to produce systemic effects. Bioavailability is a fundamental property of a pharmaceutical product for a given route of administration. It should be known and shown to be reproducible for all drug products intended to produce a systemic effect. For most drugs, the pharmacological response can be related directly to the plasma levels. 

4. DEFINITION  “ Bioavailability is a term used to indicate the fractional extent to which a dose of drug reaches its site of action or a biological fluid from which the drug has access to its site of action.” (Goodman & Gillman). “The term Bioavailability is defined as a rate & extent (amount) of absorption of unchanged drug from its dosage form.” (Brahmankar & Jaiswal)

5. Absolute bioavailability: When systemic of a drug administered orally is determined in comparison to its I.V. administration, denoted by F. Relative bioavailability:  When systemic availability of a drug after oral administration is Compared with that of oral standard of the same drug ( Solution or suspension ) and denoted by Fr.

6. OBJECTIVE It is important in the- Primary stages of development of dosage form of new drug entity to find its therapeutic utility. Determination of influence of excipients on absorption. Development of new formulations of existing drugs. Control of quality of drug products and influence of processing factors , storage and stability on absorption. Comparison of drug in different dosage forms or same dosage form of different manufacturer.

7. SIGNIFICATION Significance of Bioavailability Drugs having low therapeutic index, e.g. cardiac glycosides, quinidine, phenytoin etc. and narrow margin of safety e.g. antiarrythmics, antidiabetics, adrenal steroids, theophylline . Drugs whose peak levels are required for the effect of drugs, e.g. phenytoin, phenobarbitone, primidone, sodium valporate, anti- hypertensives, antidiabetics and antibiotics. Drugs that are absorbed by an active transport, e.g. amino acid analogues, purine analogues etc. In addition, any new formulation has to be tested for its bioavailability profile. Formulations that give sustained release of drug, formulations with smaller disintegration time than dissolution rate and drugs used as replacement therapy also warrant bioavailability testing.

8. Methods of Bioavailability Measurement Pharmacokinetic Method Plasma level time studies : Most reliable method of choice comparison to urine data method Single dose: serial blood samples collection – 2-3 half lifes Plot concentration vs time graph • For I.V. Sampling started within 5 min and subsequent samples at 15min intervals • For oral dose at least 3 points taken on absorption curve ( ascending part )

9. Parameters considered important in plasma level time studies Cmax : It is peak plasma concentration. It increases with dose as well as increase in rate of absorption. Tmax: The peak time at which Cmax atended. AUC: Area under curve explains about amount of drug.

10. 2. Urinary excretion studies: Steps involved- • collection of urine at regular intervals for 7 half lifes. • Analysis of unchanged drug in collected sample. • Determination of amount of drug at each interval and cumulative as well. Following Criteria's must be followed. • At each sample collection total emptying of bladder is necessary. Frequent sampling is essential in the beginning to compute correct rate of absorption. • The fraction excreted unchanged in urine must remain constant.

11. Pharmacodynamic methods Acute pharmacological response : When bioavailability measurement by pharmacokinetic methods is difficult, inaccurate or non reproducible this method is used. Such as ECG, Pupil diameter etc. It can be determined by dose response graphs. Responses measure for at least 3 half lifes. Therapeutic response: This method is based on observing clinical response in patients. Drawbacks : - The physiological status of subject assumed that does not change significantly over duration of study. - If multiple dose protocols are not involved. Patient receive only single dose for few days or a week - The patient s receiving more than one drug treatment may be compromised due to drug-drug interaction .

12. Bioequivalence studies  It is a relative term which denotes that the drug substance in two or more identical dosage forms, reaches the systemic circulation at same relative rate and relative extent. Types of Bioequivalence studies : In Vivo Bioequivalence studies In Vitro Bioequivalence studies

13. In Vivo Bioequivalence studies The following sequence of criteria is useful in assessing the need for in vivo studies. Oral immediate release products with systemic action - Indicated for serious conditions requiring assured response. - Narrow therapeutic margin. Unfavorable physiochemical properties e.g., Low solubility, meta stable modifications, instability etc. Non Oral immediate release products Modified release products with systemic action.

14. 2.In VITRO Bioequivalence Studies  In comparative in vitro dissolution studies. In vivo bioequivalence under certain circumstances called as biowaivers The drug product differs only in strength of the active substances it contain, provided all the following conditions hold- • The drug product has been slightly reformulated method has been slightly modified. • The drug product is in the form of solution or solubilised form (eg., elixir, syrup, tincture etc .) • In vitro dissolution rate of the new products is equivalent with that of the already approved medicinal product. Topical administration (Cream, ointment,gel ) for local effect. Oral administration but intended to be absorbed.

15. Bioequivalence Experimental study design Completely randomisation Randomized block designs Repeated measures, cross over and carry over designs Latin square designs 

16. REFERENCES Biopharmaceutics and pharmacokinetics – A Treatise, D. M. Brahmankar, Sunil B.Jaiswal . Vallabh prakashan IInd edition 315-366 Toutain, P. L., Bousquet-Me ´lou, A. Bioavailability and its assessment. J. vet. Pharmacol. Therap. 27, 455–466

17. THANK YOU