This document discusses bioavailability and bioequivalence studies. It defines bioavailability as the rate and extent of absorption of a drug from its dosage form and defines bioequivalence as two or more identical drug products reaching systemic circulation at the same rate and to the same relative extent. The document outlines various methods to assess bioavailability including plasma level-time studies and urinary excretion studies. It also discusses the objectives and types of bioequivalence studies, including in vivo and in vitro methods.

1. BIOAVAILABILITY AND BIOEQUIVALENCE STUDY
A Seminar submitted to the
Jawaharlal Nehru Technological University, Hyderabad.
In partial fulfillment of the requirements for the degree of
BACHELOR OF PHARMACY
By
MEHER UNISSA
15S61R0009
Under the guidance of
[Afshan Sultana], M. Pharm.,
Assistant Professor
Department of Biopharmaceutics and Pharmacokinetics
Anwarul Uloom College of Pharmacy
New Mallepally, Hyderabad -500 001
Affiliated to JNTUH, Approved by AICTE and PCI
22 SEPTEMBER-2018

2. BIOAVAILABILITY
AND
BIOEQUIVALENCE

3. BIOAVAILABILITY
CONTENTS –
 Brief introduction to bioavailability
 Objectives
 Methods of assessing bioavailability
BIOEQUIVALENCE
STUDIES
CONTENTS –
 Definition
 Requirements/Objectives of Bioequivalence
 Types of Bioequivalence
1. In vivo
2. In vitro

4. BIOAVAILABILITY

5. 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
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

6. OBJECTIVES-
1. Development of new formulations.
2. Determination of influence of excipients, patient related
factors and possible interaction with other drugs on the
efficiency of absorption.
3. Control of quality of a drug product during the early stages
of marketing in order to determine the influence of
processing factors, storage, stability on drug absorption.
4. Primary stages of the development of a suitable dosage
form for a new drug entity.
OBJECTIVES-
1. Development of new formulations.
2. Determination of influence of excipients, patient related
factors and possible interaction with other drugs on the
efficiency of absorption.
3. Control of quality of a drug product during the early
stages of marketing in order to determine the influence
of processing factors, storage, stability on drug
absorption.
4. Primary stages of the development of a suitable dosage
form for a new drug entity.

7. There are two types of bioavailability , they are :
• Absolute bioavailability
• Relative bioavailability
ABSOLUTE BIOAVAILABILITY ( F )
• When systemic availability of drug administered orally is
determined in comparison to its intravenous administration, is
called absolute bioavailability.
• Its determination is used to characterize a drug’s inherent
absorption properties from the extra vascular site.
Absolute bioavailability =
𝑨𝑼𝑪 𝒐𝒓𝒂𝒍 𝑫𝒐𝒔𝒆 𝒊𝒗
𝑨𝑼𝑪 𝒊𝒗 𝑫𝒐𝒔𝒆 𝒐𝒓𝒂𝒍
There are two types of bioavailability , they are :
• Absolute bioavailability
• Relative bioavailability
ABSOLUTE BIOAVAILABILITY ( F )
• When systemic availability of drug administered orally is
determined in comparison to its intravenous administration,
is called absolute bioavailability.
• Its determination is used to characterize a drug’s inherent
absorption properties from the extra vascular site.
Absolute bioavailability =
𝑨𝑼𝑪 𝒐𝒓𝒂𝒍 𝑫𝒐𝒔𝒆 𝒊𝒗
𝑨𝑼𝑪 𝒊𝒗 𝑫𝒐𝒔𝒆 𝒐𝒓𝒂𝒍

8. RELATIVE BIOAVAILABILITY ( Fr )
• When systemic availability of drug after oral
administration is compared with that of an oral
standard of same drug (such as an aqueous or non
aqueous solution or suspension) it is referred as
relative bioavailability.
• It is used to characterize absorption of drug from
its formulation.
Relative bioavailability =
𝐴𝑈𝐶 𝑡𝑒𝑠𝑡 𝐷𝑜𝑠𝑒 𝑠𝑡𝑑
𝐴𝑈𝐶 𝑠𝑡𝑑 𝐷𝑜𝑠𝑒 𝑡𝑒𝑠𝑡
RELATIVE BIOAVAILABILITY ( Fr )
• When systemic availability of drug after oral
administration is compared with that of an oral
standard of same drug (such as an aqueous or non
aqueous solution or suspension) it is referred as
relative bioavailability.
• It is used to characterize absorption of drug from its
formulation.
Relative bioavailability =
𝐴𝑈𝐶 𝑡𝑒𝑠𝑡 𝐷𝑜𝑠𝑒 𝑠𝑡𝑑
𝐴𝑈𝐶 𝑠𝑡𝑑 𝐷𝑜𝑠𝑒 𝑡𝑒𝑠𝑡

9. METHODS OF ASSESING
BIOAVAILABILITY :
• Plasma Level-Time
Studies
• Urinary Excretion
Studies
PHARMACOKINETIC
METHODS
• Acute
Pharmacological
Response
• Therapeutic Response
PHARMACODYNAMIC
METHODS
METHODS OF ASSESING
BIOAVAILABILITY :

10. 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 &
concentration of drug at the site of action
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 & concentration of drug at the site
of action

11. URINARY EXCRETION STUDIES –
o Urinary excretion of unchanged drug is directly proportional to
plasma concentration of drug.
o Thus, even if a drug is excreted to some extent (at least 10
to 20%) in the urine, bioavailability can be determined.
o Non invasive method, so better patient compliance.
Eg: Thiazide diuretics, Sulphonamides
URINARY EXCRETION STUDIES –
o Urinary excretion of unchanged drug is directly proportional to
plasma concentration of drug.
o Thus, even if a drug is excreted to some extent (at least 10 to
20%) in the urine, bioavailability can be determined.
o Non invasive method, so better patient compliance.
Eg: Thiazide diuretics, Sulphonamides

12. ACUTE PHARMACOLOGICAL RESPONSE METHOD –
• When bioavailability measurement by pharmacokinetic
method is difficult, an acute pharmacologic effect such as
effect on pupil diameter, EEG & ECG readings related to time
course of drug.
• Bioavailability can then be determined by construction of
pharmacological effect- time curve as well as dose response
graphs.
THERAPEUTIC RESPONSE METHOD –
• This method based on observing the clinical response to a
drug formulation given to patient suffering from disease.
ACUTE PHARMACOLOGICAL RESPONSE METHOD –
• When bioavailability measurement by pharmacokinetic
method is difficult, an acute pharmacologic effect such as
effect on pupil diameter, EEG & ECG readings related to time
course of drug.
• Bioavailability can then be determined by construction of
pharmacological effect- time curve as well as dose response
graphs.
THERAPEUTIC RESPONSE METHOD –
• This method based on observing the clinical response to a
drug formulation given to patient suffering from disease.

13. BIOEQUIVALENCE

14. DEFINATION –
 It refers to the drug substance in two or more
identical dosage forms, reaches systemic
circulation at the same rate and to the same
relative extent.
 That is their plasma concentration-time
profiles will be identical without significant
statistical differences.
DEFINATION –
 It refers to the drug substance in two or
more identical dosage forms, reaches
systemic circulation at the same rate and
to the same relative extent.
 That is their plasma concentration-time
profiles will be identical without significant
statistical differences.

15. ADVANTAGES –
• Minimizes the effect of inter subject variability.
• It minimizes the carry over effect.
• Requires less number of subjects to get meaningful results.
DISADVANTAGES –
• Requires longer time to complete the studies.
• Completion of studies depends on number of formulations
evaluated in the studies.
ADVANTAGES –
• Minimizes the effect of inter subject variability.
• It minimizes the carry over effect.
• Requires less number of subjects to get meaningful
results.
DISADVANTAGES –
• Requires longer time to complete the studies.
• Completion of studies depends on number of formulations
evaluated in the studies.

16. OBJECTIVES –
➢ If a new product is intended to be a substitute for an
approved medicinal product as a pharmaceutical equivalent
or alternative , the equivalence with this product should be
shown or justified.
➢ In order to ensure clinical performance of such drug
products , bioequivalence studies should be performed.
➢ Bioequivalence studies are conducted if there is:
a) A risk of bio - inequivalence and/or
b) A risk of pharmacotherapeutic failure or diminished
clinical safety.
OBJECTIVES –
➢ If a new product is intended to be a substitute for
an approved medicinal product as a
pharmaceutical equivalent or alternative , the
equivalence with this product should be shown or
justified.
➢ In order to ensure clinical performance of such
drug products , bioequivalence studies should be
performed.
➢ Bioequivalence studies are conducted if there is:
a) A risk of bio - inequivalence and/or
b) A risk of pharmacotherapeutic failure or
diminished clinical safety.

17. TYPES OF BIOEUIVALENCE STUDIES –
Bioequivalence can be demonstrated either –
• In vivo , or
• In vitro
IN VIVO BIOEQUIVALENCE STUDIES –
• Done when 2 drug products are:
In same dosage form,
Proportionally similar in active & inactive ingredients, Differ
only in strengths of the medication.
• Bioequivalence study of lower strength(s) can bewaived.
In vivo bioequivalence studies are conducted in the usual
manner as discussed for bioavailability studies, i.e. the
pharmacokinetic and the pharmacodynamic methods.

18. IN VITRO EQUIVALENCE STUDIES –
 If none of the above criteria is applicable, comparative in
vitro dissolution studies will suffice.
 In vitro studies, i.e. dissolution studies can be used in
lieu of in vivo bioequivalence under certain
circumstances, called as biowaivers (exemptions)
• Dissolution testing is a requirement for all solid oral
dosage forms and is used in all phases of development for
product release and stability testing.
• It is a key analytical test used for detecting physical
changes in an active pharmaceutical ingredient (API) and
in the formulated product.
IN VITRO EQUIVALENCE STUDIES –
 If none of the above criteria is applicable, comparative
in vitro dissolution studies will suffice.
 In vitro studies, i.e. dissolution studies can be used in
lieu of in vivo bioequivalence under certain
circumstances, called as biowaivers (exemptions)
• Dissolution testing is a requirement for all solid oral
dosage forms and is used in all phases of development for
product release and stability testing.
• It is a key analytical test used for detecting physical
changes in an active pharmaceutical ingredient (API) and
in the formulated product.

19. REFERENCES –
 Brahmankar .D.M , Sunil B.Jaiswal ,
( Biopharmaceutics and Pharmacokinetics-A- Treatise
Pg no : 236-337 )
 LeonShargel & Andrew B.C.Yu ,
( Applied Biopharmaceutics & pharmacokinetics
Pg no : 453-466 )
 V Venkateshwarlu ,
( Biopharmaceutics & pharmacokinetics
Pg no : 403-416 )

20. For lending your