Bioavailability study

The amount of drug that reaches the systemic circulation is called systemic availability.
It is a Primary stage of development of a suitable dosage form.

1. BIOAVAILABILITY Yogesh Tiwari M Pharma (Pharmaceutics) Assistant Professor VIPER, Sagar (MP) 4/27/2020 1

2. CONTENT Introduction Objectives Measurement of Bioavailability Methods for Enhancement of Bioavailability 4/27/2020 2

3. education school college “Poisons and medicine are often the same substance given with different intents.” Astrology Religious Literature 4/27/2020 3

4. INTRODUCTION Bioavailability is defined as the rate and extent of absorption of unchanged drug from its dosage form. The amount of drug that reaches the systemic circulation is called systemic availability. Bioavailability of a drug from its dosage form depends upon 3 major factors:- 4/27/2020 4

5. Cont…… 4/27/2020 5

6. OBJECTIVES 4/27/2020 6

7. MEASUREMENT OF BIOAVAILABILITY The methods useful in quantitative evaluation of bioavailability can be broadly divided in two categories:- 4/27/2020 7

8. 1.PHARMACOKINETIC METHOD This profile reflects the therapeutic effectiveness of a drug. Pharmacokinetic methods Plasma Level Time Studies Urinary Excretion Studies 4/27/2020 8

9. Cont….. Plasma Level Time Studies :- It is a most reliable method. The 3 parameter of plasma level time studies which are :- C max ( Peak Plasma Conc .) T max ( Time of Peak Plasma Conc.) AUC ( Area Under the Curve ) 4/27/2020 9

10. Drug administration Time Plasma Drug Concentration Onset of time T max Elimination phase Onset of action C max Absorption phase Area Under the Curve (AUC) MSC MEC Plasma Drug Concentration Time Profile 4/27/2020 10

11. Plasma Level Time Studies 1. C max :- ( Peak plasma concentration) The drug is sufficiently absorbed systemically to provide a therapeutic response. It is a function of both rate and extent of absorption. C max will increase as well as absorption increase. 4/27/2020 11

12. Plasma Level Time Studies 2. T max (Time of Peak Plasma Conc.) The time required to reach maximum drug concentration after drug administration. It indicates the rate of absorption. If T max decreases, the rate of absorption increases. 4/27/2020 12

13. Plasma Level Time Studies 3. AUC ( Area Under the Curve ) It gives a measure of the extent of absorption The AUC reflects the total amount of active drug that reaches the systemic circulation. The AUC is independent of the route of administration and processes of drug elimination as long as the elimination processes do not change. 4/27/2020 13

14. Plasma Level Time Studies Extent of the bioavailability can be determined by following equation:- F = Fr = Where, D- dose administered F - absolute bioavailability Fr – relative bioavailability (AUC) oral D iv (AUC) iv D oral (AUC) test D std (AUC) std D test 4/27/2020 14

15. Urinary Excretion Studies The urinary excretion of unchanged drug is directly proportional to the plasma conc. of drug. The study is particularly useful for:- Drugs extensively excreted unchanged in urine ; like Thiazide diuretics. 4/27/2020 15

16. Urinary Excretion Studies Three major parameters examined in urinary excretion data:- Rate of drug excretion in the urine ( dDu / dt ). Time for maximum urinary excretion ( Tu )max . Cumulative amount of drug excreted in the urine ( Du). 4/27/2020 16

17. Urinary Excretion Studies 1. Rate of drug excretion in the urine ( dDu / dt ). It is analogous to the C max derived from plasma level study. 2. Time for maximum urinary excretion ( Tu )max. It is analogous to the Tmax derived from plasma level data. 4/27/2020 17

18. Urinary Excretion Studies 3. Cumulative amount of drug excreted in the urine ( Du). It is related directly to the total amount of drug absorbed. Experimentally, urine samples are collected periodically after administration of a drug product. When the drug is almost completely eliminated, the plasma concentration approaches zero and the maximum amount of drug excreted in the urine, Du, is obtained. 4/27/2020 18

19. Cont…... Extent of the bioavailability can be determined by following equation:- F = Fr = Where, D- dose administered F - absolute bioavailability Fr – relative bioavailability ( Du ) oral D iv ( Du ) iv D oral ( Du ) test D std ( Du ) std D test 4/27/2020 19

20. 2.PHARMACODYNAMIC METHOD In some cases, the quantitative measurement of a drug in plasma is not available or in vitro approaches are not applicable. The following criteria for a pharmacodynamic (PD) endpoint study are important: A dose response relationship is demonstrated. Sufficient measurements should be taken to assure an appropriate PD response profile. All PD measurement assays should be validated for specificity , accuracy , sensitivity , and precision . 4/27/2020 20

21. 2.PHARMACODYNAMIC METHOD Pharmacodynamic methods Acute Pharmacological Response Therapeutic Response 4/27/2020 21

22. 2.PHARMACODYNAMIC METHOD Acute Pharmacological Response An acute pharmacodynamic effect, such as an effect on forced expiratory volume, FEV1 (inhaled bronchodilators),or skin blanching (topical corticosteroids) can be used as an index of drug bioavailability. An acute pharmacodynamic effect, such as a change in ECG reading, Pupil diameter etc. it is related to the time course of a given drug. 4/27/2020 22

23. 2.PHARMACODYNAMIC METHOD 2. Therapeutic Response Method This method is based on observing the clinical response to a drug formulation given to patients suffering from disease for which is intended to be used. 4/27/2020 23

24. METHODS FOR ENHANCEMENT OF BIOAVAILABILITY 4/27/2020 24

25. METHODS FOR ENHANCEMENT OF BIOAVAILABILITY 1. Enhancement of drug solubility Micronization Nanonization Use of surfactants Use of salt forms Use of precipitation inhibitors Solid dispersion 4/27/2020 25

26. METHODS FOR ENHANCEMENT OF BIOAVAILABILITY 2. Enhancement of drug permeability across bio-membrane 1 Lipid technologies:- 1. lipid solution and Suspension 2. Solid lipid nanoparticles 3. liposome 2 Ion Pairing 4/27/2020 26

27. METHODS FOR ENHANCEMENT OF BIOAVAILABILITY 3. Enhancement of drug stability Enteric coating Complexation Use of metabolism inhibitors 4/27/2020 27

28. Some Questions…… Describe the methods to enhance dissolution rates and bioavailability of drugs. Describe the pharmacokinetic method of estimating bioavailability using plasma sample. Mention the objective a bioavailability studies. Discuss the methods of determination of bioavailability. 4/27/2020 28

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