It is defined as “the predictive mathematical model that describes the relationship between in vitro property (such as rate & extent of dissolution) of a dosage form and in vivo response (such as plasma drug concentration or amount of drug absorbed)”.
An in-vitro in-vivo correlation (IVIVC) has been defined by the U.S. Food and Drug Administration (FDA) as "a predictive mathematical model describing the relationship between an in-vitro property of a dosage form and an in-vivo response".
United State Pharmacopoeia (USP)The establishment of a rational relationship between a biological property, or a parameter derived from a biological property produced by a dosage form, and a physicochemical property or characteristic of the same dosage form.
Food and Drug Administration (FDA) definitionIVIVC is a predictive mathematical model describing the relationship between an in vitro property of a dosage form and a relevant in vivo response. Generally, the in vitro property is the rate or extent of drug dissolution or release while the in vivo response is the plasma drug concentration or amount of drug absorbed.
An in-vitro in-vivo correlation (IVIVC) has been defined by the U.S. Food and Drug Administration (FDA) as "a predictive mathematical model describing the relationship between an in-vitro property of a dosage form and an in-vivo response".
United State Pharmacopoeia (USP)The establishment of a rational relationship between a biological property, or a parameter derived from a biological property produced by a dosage form, and a physicochemical property or characteristic of the same dosage form.
Food and Drug Administration (FDA) definitionIVIVC is a predictive mathematical model describing the relationship between an in vitro property of a dosage form and a relevant in vivo response. Generally, the in vitro property is the rate or extent of drug dissolution or release while the in vivo response is the plasma drug concentration or amount of drug absorbed.
1. Measurement of Bioavailability:
Direct and indirect methods may be used to assess drug bioavailability. The in-vivo bioavailability of a drug product is demonstrated by the rate and extent of drug absorption, as determined by comparison of measured parameters, e.g., concentration of the active drug ingredient in the blood, cumulative urinary excretion rates, or pharmacological effects.
For drug products that are not intended to be absorbed into the bloodstream, bioavailability may be assessed by measurements intended to reflect the rate and extent to which the active ingredient or active moiety becomes available at the site of action.
The design of the bioavailability study depends on the objectives of the study, the ability to analyze the drug (and metabolites) in biological fluids, the pharmacodynamics of the drug substance, the route of drug administration, and the nature of the drug product.
Pharmacokinetic and/or pharmacodynamic parameters as well as clinical observations and in-vitro studies may be used to determine drug bioavailability from a drug product.
1.1. Pharmacokinetic methods:
These are very widely used and based upon the assumption that the pharmacokinetic profile reflects the therapeutic effectiveness of a drug. Thus these are indirect methods. The two major pharmacokinetic methods are:
The major pharmacokinetic methods are:
Plasma / blood level time profile.
o Time for peak plasma (blood) concentration (t max)
o Peak plasma drug concentration (Cmax)
o Area under the plasma drug concentration–time curve (AUC)
Urinary excretion studies.
o Cumulative amount of drug excreted in the urine (Du)
o Rate of drug excretion in the urine (dDu/dt)
o Time for maximum urinary excretion (t)
C. Other biological fluids
1.2. Pharmacodynamic methods:
IT involves direct measurement of drug effect on a (patho) physiological process as a function of time. Disadvantages of it may be high variability, difficult to measure, limited choices, less reliable, more subjective, drug response influenced by several physiological & environmental factors.
They involve determination of bioavailability from:
Acute pharmacological response.
Therapeutic response.
1.3. In-vitro dissolution studies
Closed compartment apparatus
Open compartment apparatus
Dialysis systems.
1.4. Clinical observations
Well-controlled clinical trials
DISSOLUTION
Dissolution is defined as a process in which a solid substance solubilises in a given solvent.
(i.e. mass transfer from the solid surface to the liquid phase.)
Three Theories:
Diffusion layer model / Film theory
Danckwert’s model / Penetration or Surface renewal theory
Interfacial barrier model / Double barrier or Limited solvation theory
Methods For Assesment Of Bioavailability Anindya Jana
Bioavailability means the rate and extent to which the active ingredient or active moiety is absorbed from a drug product and becomes available at the site of action. For drug products that are not intended to be absorbed into the bloodstream, bioavailability may be assessed by measurements intended to reflect the rate and extent to which the active ingredient or active moiety becomes available at the site of action.
Bioavailability studies are important in the Primary stages of development of a suitable dosage form for a new drug entity, determination of influence of excipients, patient related factors & possible interaction with other drugs on the efficiency of absorption, development of new formulations of the existing drugs, 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
In this presentation I have mentioned whatever the possible relevant content/guidelines require for biowaiver application.
Citation Is done at the end of slide.
Content is up to date & true to my belief.
Thanks & Best Regards.
Anurag Pandey
B.Pharm (FACULTY OF PHARMACY, INVERTIS UNIVERSITY)
M.Pharm (INSTITUTE OF PHARMACY, NIRMA UNIVERSITY)
Email :- anurag.dmk05@gmail.com
It includes Introductory part about what is Dissolution...then Mechanism of Dissolution is elaborated...Theories of Dissolution also given..It also includes Factors affecting Dissolution profile..Along with References given below for easily searching..
1. Measurement of Bioavailability:
Direct and indirect methods may be used to assess drug bioavailability. The in-vivo bioavailability of a drug product is demonstrated by the rate and extent of drug absorption, as determined by comparison of measured parameters, e.g., concentration of the active drug ingredient in the blood, cumulative urinary excretion rates, or pharmacological effects.
For drug products that are not intended to be absorbed into the bloodstream, bioavailability may be assessed by measurements intended to reflect the rate and extent to which the active ingredient or active moiety becomes available at the site of action.
The design of the bioavailability study depends on the objectives of the study, the ability to analyze the drug (and metabolites) in biological fluids, the pharmacodynamics of the drug substance, the route of drug administration, and the nature of the drug product.
Pharmacokinetic and/or pharmacodynamic parameters as well as clinical observations and in-vitro studies may be used to determine drug bioavailability from a drug product.
1.1. Pharmacokinetic methods:
These are very widely used and based upon the assumption that the pharmacokinetic profile reflects the therapeutic effectiveness of a drug. Thus these are indirect methods. The two major pharmacokinetic methods are:
The major pharmacokinetic methods are:
Plasma / blood level time profile.
o Time for peak plasma (blood) concentration (t max)
o Peak plasma drug concentration (Cmax)
o Area under the plasma drug concentration–time curve (AUC)
Urinary excretion studies.
o Cumulative amount of drug excreted in the urine (Du)
o Rate of drug excretion in the urine (dDu/dt)
o Time for maximum urinary excretion (t)
C. Other biological fluids
1.2. Pharmacodynamic methods:
IT involves direct measurement of drug effect on a (patho) physiological process as a function of time. Disadvantages of it may be high variability, difficult to measure, limited choices, less reliable, more subjective, drug response influenced by several physiological & environmental factors.
They involve determination of bioavailability from:
Acute pharmacological response.
Therapeutic response.
1.3. In-vitro dissolution studies
Closed compartment apparatus
Open compartment apparatus
Dialysis systems.
1.4. Clinical observations
Well-controlled clinical trials
DISSOLUTION
Dissolution is defined as a process in which a solid substance solubilises in a given solvent.
(i.e. mass transfer from the solid surface to the liquid phase.)
Three Theories:
Diffusion layer model / Film theory
Danckwert’s model / Penetration or Surface renewal theory
Interfacial barrier model / Double barrier or Limited solvation theory
Methods For Assesment Of Bioavailability Anindya Jana
Bioavailability means the rate and extent to which the active ingredient or active moiety is absorbed from a drug product and becomes available at the site of action. For drug products that are not intended to be absorbed into the bloodstream, bioavailability may be assessed by measurements intended to reflect the rate and extent to which the active ingredient or active moiety becomes available at the site of action.
Bioavailability studies are important in the Primary stages of development of a suitable dosage form for a new drug entity, determination of influence of excipients, patient related factors & possible interaction with other drugs on the efficiency of absorption, development of new formulations of the existing drugs, 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
In this presentation I have mentioned whatever the possible relevant content/guidelines require for biowaiver application.
Citation Is done at the end of slide.
Content is up to date & true to my belief.
Thanks & Best Regards.
Anurag Pandey
B.Pharm (FACULTY OF PHARMACY, INVERTIS UNIVERSITY)
M.Pharm (INSTITUTE OF PHARMACY, NIRMA UNIVERSITY)
Email :- anurag.dmk05@gmail.com
It includes Introductory part about what is Dissolution...then Mechanism of Dissolution is elaborated...Theories of Dissolution also given..It also includes Factors affecting Dissolution profile..Along with References given below for easily searching..
United State Pharmacopoeia (USP)
The establishment of a rational relationship between a biological property, or a parameter derived from a biological property produced by a dosage form, and a physicochemical property or characteristic of the same dosage form.
Food and Drug Administration (FDA)
IVIVC is a predictive mathematical model describing the relationship between an in vitro property of a dosage form and a relevant in vivo response. Generally, the in vitro property is the rate or extent of drug dissolution or release while the in vivo response is the plasma drug concentration or amount of drug absorbed.
The main objective of developing and evaluating an IVIVC is to enable the
dissolution test to serve as a surrogate (alternate) for in vivo bioavailability studies in
human beings.
The applications of developing such an IVIVC are —
1. To ensure batch-to-batch consistency in the physiological performance of a drug
product by use of such in vitro values.
2. To serve as a tool in the development of a new dosage form with desired in vivo
performance.
3. To assist in validating or setting dissolution specifications (i.e. the dissolution
specifications are based on the performance of product in vivo).
There are two basic approaches by which a correlation between dissolution testing
and bioavailability can be developed:
1. By establishing a relationship, usually linear, between the in vitro dissolution and
the in vivo bioavailability parameters.
2. By using the data from previous bioavailability studies to modify the dissolution
methodology in order to arrive at meaningful in vitro-in vivo correlation.
‘Targeted drug delivery system is a special form of drug delivery system where the medicament is selectively targeted or delivered only to its site of action or absorption and not to the non-target organs or tissues or cells.’
PHARMACOKINETIC MODELS
Drug movement within the body is a complex process. The major objective is therefore to develop a generalized and simple approach to describe, analyse and interpret the data obtained during in vivo drug disposition studies.
The two major approaches in the quantitative study of various kinetic processes of drug disposition in the body are
Model approach, and
Model-independent approach (also called as non-compartmental analysis).
Biopharmaceutics: Mechanisms of Drug AbsorptionSURYAKANTVERMA2
Biopharmaceutics is defined as the study of factors influencing the rate and amount of drug that reaches the systemic circulation and the use of this information to optimise the therapeutic efficacy of the drug products.
A geographical indication (GI) is a name or sign used on certain products which corresponds to a specific geographical location or origin (e.g. a town, region, or country)
Examples: Basmati rice, Swiss watches etc
Design, optimization and in vitro evaluation of gastroretentive hollow micros...SURYAKANTVERMA2
To modify the GIT time is one of the main challenge in the development of oral controlled drug delivery system.
Gastric emptying of pharmaceutical dosage form is highly variable and dependent on the dosage form and the fed/fasted state of the stomach.
Normal gastric residence time usually ranges between 5 minutes to 2 hours.
Formulation and evaluation of fast dissolving tabletsSURYAKANTVERMA2
The concept of mouth dissolving drug delivery systems (MDDDS) or fast dissolving tablets emerged with an objective to improve patient’s compliance.
These dosage forms rapidly disintegrate and/or dissolve to release the drug as soon as they come in contact with saliva, thus obviating the need for water during administration, an attribute that makes them highly attractive for pediatric and geriatric patients.
Microsoft Windows, or simply Windows, is a metafamily of graphical operating systems developed, marketed, and sold by Microsoft. It consists of several families of operating systems, each of which cater to a certain sector of the computing industry with the OS typically associated with IBM PC compatible architecture. Active Windows families include Windows NT and Windows Embedded; these may encompass subfamilies, e.g. Windows Embedded Compact (Windows CE) or Windows Server. Defunct Windows families include Windows 9x, Windows Mobile and Windows Phone.
The greenhouse effect is a process by which thermal radiation from a planetary surface is absorbed by atmospheric greenhouse gases, and is re-radiated in all directions.
“A GMP is a system for ensuring that products are consistently produced and controlled according to quality standards. It is designed to minimize the risks involved in any pharmaceutical production that cannot be eliminated through testing the final product”.
Introduction to environment and environmental studiesSURYAKANTVERMA2
“Environmental studies” is the scientific study of our environment and our place in it.
Definition: “Environmental studies” is the study of environmental issues.
It has broader coverage than environmental science and includes social aspects of environment also.
Natural resources are materials and components (something that can be used) that can be found within the environment. Every man-made product is composed of natural resources (at its fundamental level). A natural resource may exist as a separate entity such as fresh water, and air, as well as a living organism such as a fish, or it may exist in an alternate form which must be processed to obtain the resource such as metal ores, oil, and most forms of energy.
Environmental Pollution can be defined as any undesirable change in physical, chemical, or biological characteristics of any component of the environment i.e. air, water, soil which can cause harmful effects on various forms of life or property.
Pollution: The term pollution can be defined as influence of any substance causing nuisance, harmful effects, and uneasiness to the organisms
Pollutant: Any substance causing Nuisance or harmful effects or uneasiness to the organisms, then that particular substance may be called as the pollutant.
EnvironmentalPollutioncanbedefinedasanyundesirablechangeinphysical,chemical,or biological characteristics of any component of the environment i.e.air,water, soil which can cause harmful effects on various forms of life or property.
Water (prevention and control of pollution) act, 1974SURYAKANTVERMA2
AnActtoprovideforthepreventionandcontrolofwaterpollutionandthemaintainingorrestoringofwholesomenessofwater,for the establishment, with a view to carrying out the purposes aforesaid, of Boards for the prevention and control of water pollution,forconferringonandassigningtosuchBoardspowersandfunctionsrelatingtheretoandformattersconnectedtherewith.
“ Bioavailability-
means the rate and extent to which the active ingredient or active moiety is absorbed from a drug product and becomes available at the site of action."
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
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Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
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Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
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These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
micro teaching on communication m.sc nursing.pdfAnurag Sharma
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The prostate is an exocrine gland of the male mammalian reproductive system
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Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
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2. In vitro- in vivo correlations (IVIVC)
Criteria for IVIVC
Objective of IVIVC
Levels of IVIVC
BCS for Immediate - Release Drug Product and IVIVC
Expectations.
BCS for Extended - Release Drug Product and IVIVC
Expectations.
Applications of IVIVC.
3. In vitro- in vivo correlations (IVIVC):
In IVIVC, "C" denotes "Correlation", which means "the
degree of relationship between two variables". This term does
not limit a relationship to only the linear type, but allows for
non-linear relationships as well.
It is defined as “the predictive mathematical model that
describes the relationship between in vitro property (such as
rate & extent of dissolution) of a dosage form and in vivo
response (such as plasma drug concentration or amount of
drug absorbed)”.
The main objective of developing and evaluating IVIVC is to
use dissolution test to serve as alternate for in vivo study in
human beings.
4. In vitro- in vivo correlations (IVIVC):
USP definition
“The establishment of rational relationship b/w a biological
property or a parameter derived from a biological property
produced by a dosage form and physicochemical property of
same dosage form”
Conceptually, IVIVC describes a relationship between the in
vitro dissolution / release versus the in vivo absorption.
FDA definition
“A predictive mathematical model describing relationship
between in-vitro property of a dosage form and in-vivo
response.”
5. In vitro- in vivo correlations (IVIVC):
BASIC:-
Simply a mathematical model describing the relationship
b/w in vitro and in vivo properties of drug.
In vitro –in vivo correlation can be achieved using
Pharmacological correlation
“Based on clinical observations”
Semi quantitative correlation
“Based on the drug blood levels or urinary excretion data”
Quantitative correlation
“Arising from absorption kinetics and calculation of in vivo
dissolution rate and absorption rate constants”
6. In vitro- in vivo correlations (IVIVC):
CRITERIA FOR IVIVC
•Successful IVIVC can be developed when in-vitro
dissolution is rate limiting step in absorption and
appearance of drug in in- vivo circulation following oral
or other routes of administration.
•These studies are to be conducted during the early
stages of drug product development in order to select the
most effective formulation and to establish appropriate
dosage regimen.
•The release- controlling excipients in the formulations
should either be identical or very similar.
7. In vitro- in vivo correlations (IVIVC):
OBJECTIVE OF IVIVC
•To reduce the number of human studies during the
formulation development.
•To serve as a surrogate for in vivo bioavailability
•To support biowaivers.
•To validates the use of dissolution methods and
specification settings(This is because the IVIVC includes in
vivo relevance to in vitro dissolution specifications).
•To assist quality control for certain scale-up and post-
approval changes (SUPAC).
• Due to all above objective, such IVIVC leads to
1. Shortens the drug development period,
2. Economizes the resources and
3. Leads to improved product quality.
8. In vitro- in vivo correlations (IVIVC):
Correlations of IVIVC:
1. Correlations based on the plasma level data
2. Correlations based on the urinary excretion data
3. Correlations based on the pharmacologic response
Levels of IVIVC:
Level A: The highest category of correlation. It represents
point to point correlation between in vitro dissolution and in
vivo rate of absorption.
The data treatment involves a two stage Deconvolution
Method.
1. Estimation of the in vivo absorption profile using Wagner-
Nelson or Loo-Riegelman method
2. Comparison of fraction of drug absorbed (Fa) and fraction
of drug dissolved.
9. In vitro- in vivo correlations (IVIVC):
Advantages:
Serves as alternate for in vivo study, change in manufacturing
Procedure or formula can be justified without the need of
additional human studies.
Providing process control and quality assurance
Determining stable release characteristics of the product over
time.
Level B: The mean in vitro dissolution time is compare with
mean in vivo residence time. It is not point to point correlation.
Data can be used for quality control standards.
A predictive model for relationship between summary
parameters that characterize the in-vitro and in-vivo time
course.
10. In vitro- in vivo correlations (IVIVC):
•No point to point correlation
• It compares
1. MDT vitro to MDT vivo,
2. MDT vitro to MRT,
3. In-vitro Dissolution Rate Constant.
This is of limited interest and least useful for regulatory
purposes because more than one kind of plasma curve
produces similar MRT.
Level C: Mathematical model of relationship between the
amount of drug dissolved in-vitro at a particular time and a
summary pharmacokinetic parameter that characterizes in-
vivo time course. (e.g., Cmax, Tmax, T1/2 or AUC).
11. In vitro- in vivo correlations (IVIVC):
It is single point correlation. e.g. t50%, Tmax, Cmax. This
level is only useful as guide for formulation development or
quality control.
Level C correlations can be useful in the early stages of
formulation development when pilot formulations are
being selected.
Lowest correlation level.
Does not reflect a complete shape of plasma concentration
time curve.
MULTIPLE Level C: It relates one or more pharmacokinetic
parameters to the percent drug dissolved at several time points
of dissolution profile and thus may be more useful.
If a multiple Level C correlation is possible, then a Level A
correlation is also likely and is preferred.
12. Biopharmaceutical Classification System (BCS)
for Immediate - Release Drug Product and In
vitro- in vivo correlations (IVIVC) Expectations:
CLASS SOLUBILI
TY
PERMEAB
ILITY
IVIVC Expectations for Immediate-
Release Drug Product
Possibility of
predicting IVIVC
from dissolution
data
I High High IVIVC expected, if dissolution rate
is slower than gastric emptying
rate, otherwise limited or no
correlation.
Yes
II Low High IVIVC expected, if in vitro
dissolution rate is similar to in vivo
dissolution rate, unless dose is very
high.
Yes
III High Low Absorption (permeability) is rate
determining and limited or no
IVIVC with dissolution.
No
IV Low Low Limited or no IVIVC is expected. No
13. Biopharmaceutical Classification System (BCS)
for Extended - Release Drug Product and In vitro-
in vivo correlations (IVIVC) Expectations:
CLASS SOLUBILITY PERMEABILITY Level of IVIVC
I High and site
independent
High and site independent IVIVC Level A expected
II High and site
independent
Dependant on site and
narrow absorption window
IVIVC Level C expected
III Low and site
independent
High and site independent IVIVC Level A expected
IV Low and site
independent
Dependant on site and
narrow absorption window
Little or no IVIVC
Va: Acidic Variable Variable Little or no IVIVC
Vb: Basic Variable Variable IVIVC Level A expected
14. Applications of IVIVC:
A. IVIVC IN DRUG DELIVERY
a) Early stages of drug delivery technology development
b) Formulation assessment
c) Dissolution specifications
d) FUTURE BIOWAIVERS : for minor formulation and process
changes
e) Ivivc parenteral drug delivery : causes of failure of parenteral
IVIVC.
i. Burst Release
ii. Potent Drugs & Chronic Therapy
iii. Limited volume of tissue fluids and Area of absorption at
the site of administration, unlike following the oral route of
administration. Therefore, it is very difficult to specify the in
vitro dissolution conditions that reflect the observed
differences in the in vivo plasma profiles corresponding to
the in vitro release profiles.
15. Applications of IVIVC:
A. NEW IVIVC APPLICATIONS
a) IVIVC for transdermal estradiol systems (novel
pharmaceuticals)
b) Why IVIVC fail for immediate release dosage form
c) Dissolution simulators
i. Gronings model
ii. Sartorius dissolution simulator
iii. Sartorius membrane filter solubility simulator
iv. Sartorius membrane filter absorption simulator.