Bioavailability and

bioequivalence
Presented by: Azka Fatima and Safia
Presented to: Dr. Ikrima Khalid
Department of Pharmaceutics,
Faculty of Pharmaceutical Sciences,
Government College University, Faisalabad.
Bioavailability
 The rate and extent to which the active ingredient of therapeutic
moiety is absorbed from a drug product and becomes available at the
site of action. (FDA Official Statement in 1977)
 The rate at which, and the extent to which the drug substance and/or
its active metabolites reach(es) the systemic circulation. (International
Consensus Statement)
 It is denoted by “F”.
Why we care about bioavailability?
• The “true dose” is not the drug that swallowed; but is the drug
available to exert its effect.

Bioavailable fraction (F): It refers to the fraction of administered dose

that enters the systemic circulation.
F = Bioavailable dose/ administered dose
Objectives
It is important in the
o Primary stages of development of dosage form of new drug entity to find
its therapeutic utility
o Development of new formulations of existing drug
o Determination of influence of excipients, patient related factors and
possible interactions with other drugs on absorption.
o Control of quality of drug products during the early stage of marketing
and influence of processing factors such as storage and stability on drug
absorption.
o Comparison of drug in different dosage forms or same dosage form of
different manufacturers
Types of bioavailability
Absolute bioavailability
 Compares the bioavailability of drug in systemic circulation following
oral administration with the drug following intravenous
administration
 For drugs administered intravenously, bioavailability is 100%
 Calculated by using the following formula
Fab = (AUC)oral × (Dose)i.v/ (AUC)i.v × (Dose)oral
Conti…
Relative bioavailability
 When systemic availability of a drug after oral administration is
compared with that of standard oral administration of the same drug
 It is denoted by "Fr”
 Calculated by using the following formula
Fr = (AUC)drug / (AUC)standard
Factors affecting the bioavailability
• It depends on three factors:
Physicochemical properties of the drug
Patient related factor
Route of administration
Methods for assessing bioavailability
Pharmacokinetics methods (Indirect method) – the assumption
that the pharmacokinetics profile reflects the therapeutics
effectiveness of a drug
 Plasma level-time studies
 Urinary excretion studies
Pharmacodynamics methods (Direct method) – Measurement
of drug effects on a physiological process as a function of time
 Acute pharmacological studies
 Therapeutic response
Pharmacokinetics methods
Plasma level-time studies
• Most common type of bioavailability study
• Based on the assumption that there is direct relationship between the
concentration of drug in blood or plasma and the concentration of
drug at the site of action
• Parameters considered important in plasma level-time studies
o Cmax
o Tmax
o AUC
Conti…
Urinary excretion studies
• based on the principle that urinary excretion of unchanged drug is
directly proportional to the plasma concentration of drug
• It can be performed if
- At least 20% of administered dose is excreted unchanged in urine
- Drugs that have urine as site of action e.g. urinary antiseptics like
nitrofurantoin
• Parameters considered important in urinary excretion studies
1. (Dxu/dt)max
2. (Tu)max
3. Xu
Pharmacodynamics methods
Acute pharmacological studies
• Determined by dose response graph
• Responses measure for at least three half lives

Therapeutic response
• Based on observing clinical response in patient
• Have several drawbacks
BIOEQUIVALENCE;
BIOEQUIVALENCE TERMS;
• Chemical equivalence;
• Two or more drug products contain the same labelled chemical substance as
an active ingredient in the same amount.
• Parmaceutical equivalence;
• If two or more than two dosage forms are identical in strength, purity,
dissolution, disintegration and content uniformity. They may differ in
excipients.
• Therapeutic equivalence;
• Two or more drug products contain same active ingredient elicit the same
pharmacological response.
METHODS FOR ASSESSING
BIOEQUIVALENCE;
• Two types of bioequivalence study;
• In-vivo study.
Plasma drug concentration.
Urinary drug excretion.
• In-vitro study.
Drug release or dissolution studies.
B.E STUDY DESIGN;
• The study is performed in;
• Normal,
• Healthy,
• Male and female volunteer,
• Age 20-50 years,
• Weight 54-91 kgs,
• And of normal body fluids.
Conti…
• 1. fasting study.
• 2. food intervention.
• 3. multiple dose (steady-state) study.
• 4. crossover design.
1.FASTING STUDY;
• The subject should be in the fasting state at least 10 hours overnight
fast prior to drug administration and should fast 2-4 hours after
dosing.

2. FOOD INTERVENTION;
• Following the overnight fast, subjects are given the recommended
meal ( high calorie meal) 30 minutes before dosing.
3. Multiple dose study;
• For this study type, several doses are administered and samples are
taken.

• ADVANTAGE;
• more drug in plasma--------- easy assay.
• DISADVANTAGE;
• More time taking.
• More samples should be collected.
4. CROSS OVER STUDY DESIGN;
• Each subject receives the test and refrence drug product.
• Between 1st and 2nd study there is a period of one week known as
wash out period.
WHY?
• Drug exhibit narrow therapeutic ratio.
• Physicochemical problems of drug;
Dissolution rate
Particle size
Solubility
Active to excipient ratio
Pharmacokinetic problems of drug.
ADME Problems.
References
Applied Biopharmaceutics and Pharmacokinetics, 7th Edition.pdf
https://www.slideshare.net/VishalShelke11/bioavailability-bioequival
ence-studies
https://www.slideshare.net/bharathpharmacist/bioavailability-ppt-39
685808
https://www.slideshare.net/AdityaSharma1550/bioavailability-bioeq
uivalence-ppt