Jayaaaa Methods of Bioavailability

MAHARSHI DAYANAND
UNIVERSITY
METHODS OF DETERMINING BIOAVAILABILTY
Submitted To Submitted to
Prof. Arun Nanda Sir Aman kumar

M. Pharm Ist Year
(IP)
DEPARTMENT OF PHARMACEUTICAL SESSION 2022-2023

1 1
INTRODUCTION:-
 Bioavailability is defined as rate and extent of absorption of

unchanged drug from it's dosage form and become available at the site
of action.
 Bioavailability of a drug from it's dosage form depends upon 3 major
factors:
• Pharmaceutical factors
• Patient related factors
• Route of administration
DEPARTMENT OF PHARMACEUTICAL SCIENCES,MDU,ROHTAK SESSION 2022-2 2

2023
OBJECTIVES OF BIOAVAILABILITY STUDIES:-
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
SESSION
DEPARTMENT OF PHARMACEUTICAL SCIENCES,MDU,ROHTAK 2022-2023 3 3
FACTOR AFFECTING BIOAVAILABILITY
SESSION
2022-2023 4 4
DEPARTMENT OF PHARMACEUTICAL SCIENCES,MDU,ROHTAK
PHARMACEUTICAL FACTORS:-
A. PHYSICOCHEMICAL PROPERTIES OF THE DRUG.

1.Drug solubility & dissolution rate.
2.Particle size & effective surface area.
3.Polymorphism & Amorphism.
Amorphous > metastable > stable
4. Pseudopolymorphism (Hydrates / Solvates)
Anhydrates > hydrates e.g. Theophylline, Ampicillin
Organic solvates> non solvates e.g. fludrocortisone
5. Salt form of the drug.
Weakly acidic drugs-strong basic salt e.g.barbiturates,
Weakly basic drugs-strong acid salt
6. Lipophilicity of the drug.
7.pKa of the drug & pH.
SESSION
PHARMACEUTICAL FACTORS:-
B) DOSAGE FORM CHARACTERISTICS & PHARMACEUTIC

INGREDIENTS:
1. Disintegration time (tab/cap)
2. Dissolution time
3. Manufacturing variables.
4. Pharmaceutic ingredients (excipients / adjuvants)
5. Nature & type of dosage form.
Solutions> Emulsions> Suspensions> Cap> Tab> Enteric Coated Tab >
Sustained Release
6. Product age & storage conditions
DEPARTMENT OF PHARMACEUTICAL SCIENCES,MDU,ROHTAK SESSION 6 6

2022-2023
PATIENT RELATED FACTORS:-
1. Age
2.Gastric emptying time.
3.Intestinal transit time.
4. Gastrointestinal pH .(HCL > Acetic > citric)
5. Disease States.
6. Blood flow through the gastrointestinal tract.
7.Gastrointestinal contents:
 Other drugs.
 Food.
 Fluids
 Other normal G.I contents
SESSION
ROUTES OF ADMINISTRATION :
Parenteral > Rectal > Oral > Topical
SESSION
METHODS OF ASSESSING BIOAVAILABILITY:-
SESSION
DEPARTMENT OF PHARMACEUTICAL SCIENCES,MDU,ROHTAK 9 9
2022-2023
1.PK METHODS- (A) PLASMA LEVEL-TIME STUDIES
Pharmacokinetic methods are widely used and based on assumption that

Pharmacokinetic profile reflects the therapeutic effectiveness of a drug.
Plasma Level- Time Studies:
 Most common type of human bioavailability studies.
 Based on the assumption that there is a direct relationship between the
concentration of drug in blood or plasma and the concentration of drug at the
site of action.
 Following the administration of a single dose of a medication, blood samples
are drawn at specific time intervals and analyzed for drug content.
SESSION
DEPARTMENT OF PHARMACEUTICAL SCIENCES,MDU,ROHTAK 2022-2023 10
10
CONT.
 A profile is constructed showing the concentration of drug in blood

at the specific times the samples were taken.
 Bioavailability (the rate and extent of drug absorption) is generally
assessed by the determination of following three parameters.
These are:-
Cmax (Peak plasma concentration)
tmax(time of peak)
Area under curve
SESSION
11
PHARMACOKINETIC PARAMETERS:-
Cmax :-(Peak plasma drug concentration)

 Maximum concentration of the drug obtained after the
administration of single dose of the drug.
 Expressed in terms of μg/ml or mg/ml.
Tmax : -(Time of peak plasma conc.)
 Time required to achieve peak concentration of the drug after administration.
 Gives indication of the rate of absorption.
 Expressed in terms of hours or minutes.
AUC:- Is the measurement of the extent of the drug bioavailability
 It is the area under the drug plasma level-time curve from t =0 & t = ∞, and is
equal to the amount of unchanged drug reaching the general circulation
divided by the clearance
SESSION
PLASMA DRUG CONCENTRATION-TIME PROFILE
SESSION 13
DEPARTMENT OF PHARMACEUTICAL SCIENCES,MDU,ROHTAK 2022-202313
MEASURMENTS OF AUC
A.Trapezoidal method:
 Most common method of estimating AUC.
 Divide the plasma conc-time curve into several trapezoids.
 Count the trapezoids & find the area.
 Total area of the trapezoids will approximate the area under the
curve.
 More number of trapezoids formed more accurate will be the result.
The area of one trapezoid between time t1 and t2 is
= C1 +C2 (t2 – t1 )
2
SESSION 14
14
b) CUT & WEIGH METHOD:
 Preparing calibrated plot by cutting squares of graph &weights are

recorded & plotted against weight Vs area.
 Sample curve is cut & weight is recorded.
 By interpolation method area of sample graph is found.
SESSION 15
15
c).PLANIMETER:-
•Instrument for mechanically measuring the area under the curve.

•Measures area by tracing outline of curve.
Disadvantage:-
Degree of error is high due to instrumental & human error.
d)COUNTING THE SQUARE :-
• Total no. of squares enclosed in the curve is counted.

• Area of each square determined using relationship:
AREA=(height) (width)
SESSION 16
16
Estimation of Area Under Plasma Concentration versus Time Curve
by the Method of
Counting Squares.
SESSION
CONT.
 The extent of bioavailability can be determined by the following equations:
 For single dose study:-
F =[AUC] oral D (iv)
[AUC] iv. D (oral)
Fr= [AUC] test D std
[AUC]std D test
 For multiple dose study:-
Fr= (AUC) test. Dstd .Ґtest
(AUC) std. Dtest.Ґstd.
 Where [AUC] values are area under the plasma level time curve of one dosing
interval in a multiple dosage regimen, after reaching the steady-state. And T is
the dosing interval.
SESSION
(B)Urinary Excretion Studies:
 Urinary excretion of unchanged drug is directly proportional to plasma

concentration of drug.
 Thus, even if a drug is excreted to some extent (at least 10 to 20%) in the
urine, bioavailability can be determined.
eg: Thiazide diuretics, Sulphonamides.
 Method is useful when there is lack of sufficiently sensitive analytical

technique to measure drug concentration.
 Noninvasive method, so better patient compliance.
SESSION 19
19
Three Important Parameters in urine excretion
data for single dose study:-
1.(dxu/dt)max :(Maximum urinary excretion rate
• Its value increases as rate and/or extent of absorption increases.
• Obtained from peak of plot between rateof excretion versus
midpoint time of urine collection period.
2.(tu) max:
• Time for maximum excretion rate
• Its value decreases as absorption rate increases.
• Analogues of tmax of plasma level data.
• Related to AUC of plasma level data.

• It increases as the extent of absorption increases.
DEPARTMENT OF PHARMACEUTICAL SCIENCES,MDU,ROHTAK SESSION 20 20

2022-2023
The extent of bioavailability is calculated from equation :
For single dose study:
For multiple dose study:
SESSION 21
21
2.PHARMACODYNAMIC METHODS:-
(A) Acute Pharmacodynamic Effect
 This method is used when the quantitative measurement of drug in plasma or

urine lacks an assay with sufficient accuracy and reproducibility.
 For locally acting, non systemically absorbed drug products, such as topical
corticosteroids, plasma drug concentrations may not reflect the bioavaibility of
the drug at the site of action.
 The use of acute pharmacodynamic effect to determine bioavailability requires
demonstration of dose response curve.
 Bioavailability is determined characterization of dose response curve.
SESSION
DEPARTMENT OF PHARMACEUTICAL SCIENCES, MDU, ROHTAK 2022-2023 22 22
DOSE RESPONSE CURVE:-
SESSION
DISADVANTAGES:-
 It tends to be more variable.

 Observed response may be due to an active metabolite
whose concentration is not proportional to concentration
of parent drug.
SESSION
24
(B)THERAPEUTIC RESPONSE METHOD:-
 This method based on observing the clinical response to a drug
formulation given to patient suffering from disease.
Drawbacks:
 The major drawbacks of this method is that quantitation of observed
response is too improper to allow for reasonable assessment of
relative bioavailability between two dosage forms of the same drug.
E.g.: Anti-inflammatory drugs.
SESSION
DEPARTMENT OF PHARMACEUTICAL SCIENCES,MDU,ROHTAK 25
2022-2023 25
REFERENCES:-
 https://www.slideshare.net/AnindyaJana/methods-for-assesment-of-
bioavailability
.
 https://www.slideshare.net/BipulDeka/bioavailabilityppt-1409300029
53phpapp012
.
 www.chatgpt//bioavailabilty assessment methods-12-svj.com.
 https://www.slideshare.net/shikhasingh121/measurement-of-bioavail
ability-72997745 SESSION
DEPARTMENT OF PHARMACEUTICAL SCIENCES,MDU,ROHTAK 26 26
2022-2023
27

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MAHARSHI DAYANAND

METHODS OF DETERMINING BIOAVAILABILTY

Prof. Arun Nanda Sir Aman kumar

DEPARTMENT OF PHARMACEUTICAL SESSION 2022-2023

 Bioavailability is defined as rate and extent of absorption of

• Patient related factors

DEPARTMENT OF PHARMACEUTICAL SCIENCES,MDU,ROHTAK SESSION 2022-2 2

• Development of new formulations of existing drugs.

• Control of quality of drug products and influence of processing factors,

A. PHYSICOCHEMICAL PROPERTIES OF THE DRUG.

B) DOSAGE FORM CHARACTERISTICS & PHARMACEUTIC

DEPARTMENT OF PHARMACEUTICAL SCIENCES,MDU,ROHTAK SESSION 6 6

Parenteral > Rectal > Oral > Topical

Pharmacokinetic methods are widely used and based on assumption that

 A profile is constructed showing the concentration of drug in blood

Cmax :-(Peak plasma drug concentration)

 Preparing calibrated plot by cutting squares of graph &weights are

•Instrument for mechanically measuring the area under the curve.

d)COUNTING THE SQUARE :-

• Total no. of squares enclosed in the curve is counted.

 Urinary excretion of unchanged drug is directly proportional to plasma

 Method is useful when there is lack of sufficiently sensitive analytical

 Noninvasive method, so better patient compliance.

• Related to AUC of plasma level data.

DEPARTMENT OF PHARMACEUTICAL SCIENCES,MDU,ROHTAK SESSION 20 20

For single dose study:

For multiple dose study:

(A) Acute Pharmacodynamic Effect

 This method is used when the quantitative measurement of drug in plasma or

 It tends to be more variable.

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