This document compares different methods for comparing dissolution profiles of drug products. It defines dissolution profile comparison and its objectives such as developing bioequivalent products and in vitro-in vivo correlations. Graphical, statistical, model-dependent and model-independent methods are described. The most common model-independent method is the f2 similarity factor test recommended by the FDA, which provides a single value to determine if two dissolution profiles are similar based on the percent dissolved over time. Proper selection of time points and criteria for coefficient of variation are important for f2 testing.
Biopharmaceutic considerations in drug product design and In Vitro Drug Produ...PRAJAKTASAWANT33
Introduction, biopharmaceutic factors affecting drug bioavailability, rate–limiting steps in drug absorption, physicochemical nature of the drug formulation factors affecting drug product performance
drug execipent compatibilty studies is of prime importance for the better formulation of the new drug and also for reducing cost by verfication of the data at the earlier atage.
this presentation will give the brief explanation of the goal, importance, dteps involve to studi the drug execient compatibility studies with different examples suitable accordiingly.
Biopharmaceutic considerations in drug product design and In Vitro Drug Produ...PRAJAKTASAWANT33
Introduction, biopharmaceutic factors affecting drug bioavailability, rate–limiting steps in drug absorption, physicochemical nature of the drug formulation factors affecting drug product performance
drug execipent compatibilty studies is of prime importance for the better formulation of the new drug and also for reducing cost by verfication of the data at the earlier atage.
this presentation will give the brief explanation of the goal, importance, dteps involve to studi the drug execient compatibility studies with different examples suitable accordiingly.
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
The release of the drug substance from the drug product leading to the bioavailability of the drug substance. The assessment of drug product performance is imp. Since bioavailability is related both to the pharmacodynamic responses and the adverse events. The performance tests relate the quality of a drug product to clinical safety and efficacy.
Bioavailability studies are drug product performance studies used to define
the effect of changes in the physicochemical properties of the drug substance, the formulation of the drug, and the manufacturing process of the drug product.
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
The release of the drug substance from the drug product leading to the bioavailability of the drug substance. The assessment of drug product performance is imp. Since bioavailability is related both to the pharmacodynamic responses and the adverse events. The performance tests relate the quality of a drug product to clinical safety and efficacy.
Bioavailability studies are drug product performance studies used to define
the effect of changes in the physicochemical properties of the drug substance, the formulation of the drug, and the manufacturing process of the drug product.
An in vitro – in vivo correlation (IVIVC) is defined by the U.S Food and Drug Administration (FDA) as a predictive mathematical model describing the relationship between the in vitro property of an oral dosage form and relevant in vivo response.
IN-VITRO-IN VIVO CORRELATION (IVIVC).pptxRAHUL PAL
An in vitro – in vivo correlation (IVIVC) is defined by the U.S Food and Drug Administration (FDA) as a predictive mathematical model describing the relationship between the in vitro property of an oral dosage form and relevant in vivo response.
INTRODUCTION
DRUG DISSOLUTION PROCESS
DISSOLUTION PROFILES COMPARISON
DISSOLUTION MODELS/METHODS TO COMPARE DISSOLUTION PROFILE WITH PROPER CLASSIFICATION & EXPLANATIONS
CONCLUSION
It is a graphical represents in terms of (Concentration Vs Time) of complete release of API from a dosages form in a appropriate selected dissolution medium, i.e., in short it is the measure of the release of API form a dosage from with respect to time
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".
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.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
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.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
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TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...
Dissolution profile comparison
1. DISSOLUTION PROFILE
COMPARISON
SUBMITTED TO SUBMITTED BY
DR JAVED ALI MOHD IMRAN
DEPARTMENT OF PHARMACEUITCS MPHARM II SEMESTER
SPER , JAMIA HAMDARD DEPARTMENT OF
PHARMACEUTICS
NEW DELHI SPER , JAMIA HAMDARD
3. DISSOLUTION PROFILE COMPARAISON
Definition
It is graphical representation in terms of [concentration
vs. time] of complete release of A.P.I. from a dosage form
in an appropriate selected dissolution medium.
4. OBJECTIVE OF DISSOLUTION PROFILE
COMPARISON
Development of bioequivalent product.
Demonstrating equivalence after change in formulation of the
drug product.
To Develop in vitro-in vivo correlation which can help to reduce
the costs, speed-up product development and reduced the need
of perform costly bioavailability human volunteer studies.
To stabilize final dissolution specification for the pharmacological
For optimizing the dosage formula by comparing the dissolution
profiles of various formulas of the same A.P.I
5. CONTINUED….
Biowaiver of drug product of lower dose strength in proportion to
higher dose strength drug product containing same active
ingredient and excipients.
FDA has placed more emphasis on dissolution profile
comparison in the field of post approval changes and biowaivers
(e.g. Class I drugs of BCS classification are skipped off these
testing for quicker approvalby FDA ).
The most important application of the dissolution profile is that
by knowing the dissolution profile of particular product of the
BRAND LEADER, we can make appropriate necessary change in
our formulation to achieve the same profile of the BRAND
LEADER.
7. GRAPHICAL METHOD
In this method we plot graph of Time V/S concentration of solute
(drug) in the dissolution medium or biological fluid.
The shape of two curves is compared for comparison of
dissolution pattern and the concentration of drug at each point is
compared for extent of dissolution.
If two or more curves are overlapping then the dissolution profile
is comparable.
If difference is small then it is acceptable but higher differences
indicate that the dissolution profile is not comparable.
8.
9. STATISTICAL ANALYSIS
1.Student’s t-Test:
The test under the student t-Test are ;
a) One sample t-test
b) Paired t-test
c) Unpaired t-test
The equation for the t is
t = [ X – μ ] / S / √N
Where X is sample mean
N is sample size
S is sample standard deviation
µ is population standard deviations ,
10. ANOVA METHOD (ANAYSIS OF
VARIANCE )
• This test is generally applied to different groups of
data. Here we compare the variance of different
groups of data and predict weather the data are
comparable or not.
• Minimum three sets of data are required. Here first we
have to find the variance within each individual group
and then compare them with each other.
11. MODEL DEPENDENT METHOD
1. Zero order kinetics ( osmotic system , transdermal system)
2. First order kinetics (water soluble drug in polymer matrix)
3. Hixon – Crowell model (Erodible matrix formulation)
4. Higuchi model (Diffusion matrix formulation)
1. Baker-Lonsdale model(microspheres , microcapsules)
2. Korsmeyer –Peppas model
12. ZERO ORDER KINETICS
Zero order A.P.I. release contributes drug release from dosage for
that is independent of amount of drug in delivery system. ( i.e.,
constant drug release) i.e.,
A0-At = Kt
Where ,
A0 = initial amount of drug in the dosage form;
At = amount of drug in the dosage form at time ‘t’
k = proportionality constant
This release is achieved by making:-
Reservoir Diffusion systems
Osmotically Controlled Devices.
13. ZERO ORDER RELEASE MODEL
1.Drug Release Rate
• Independent of concentration
2. Graphical representation
• %CDR VS TIME.
• Straight line obtain.
15. HIGUCHI MODEL
• Higuchi proposed this model in 1961 to describe the drug release
from the matrix system. It is developed to study the release of the
water soluble and low soluble drugs incorporated in semisolids
and solid matrices .
Higuchi proposed the equation which is –
Q = A √ D (2C – Cs) Cs . T
Where ,
Q = Amount of drug release in time t per unit area A
C = Initial drug concentration
Cs =Drug solubility in matrix media
D = Diffusivity of the drug molecules
16. KORSMEYER PEPPPAS MODEL
The simple relationship which described the drug release from the polymeric
system equation was derived by Korsmeyer et al in 1983. It is used to described
the first 60% release of the drug .
The equation is given as –
Mt / M∞ = Ktn
Where ,
Mt / M∞ = Fraction of drug release at time t
K = Drug release constant
n = Release exponent
The n value is used to characterize the drug release for cylindrical matrices and
the n value characterize the release mechanism of drug as described
17. n indication
Less than 0.45 Quasi fickian
0.45 Fickian diffusion
0.45<n<0.89 Non fickian diffusion
0.89-1 zero order Non fickian case 2
>1 Non fickian super case 2
n is estimated as linear regression of log (mt/m) versus log T
20. MODEL INDEPENDENT METHOD
1. PAIREDWISE PROCEDURE
• Similarity factor (F2)
• Dissimilarity factor (F1)
Dissimilarity factor (F1) as defined by FDA calculates the % difference between 2 curves at
each time point and is a measurement of the relative error between 2 curves.
Where , n = number of time points
Rt = % dissolved at time t of reference
product (pre change)
Tt = % dissolved at time t of test product
(post change)
The f1 value is equal to zero when the test and reference profiles are identical and
increases as the two profiles become less similar.
21. The similarity factor (f2) as defined by FDA is logarithmic reciprocal square root
transformation of sum of squared error and is a measurement of the similarity in the
percentage (%)
dissolution between the two profiles.
Where ,n = number of time points
Rt = % dissolved at time t of reference product (pre change)
Tt = % dissolved at time t of test product (post change)
The f2 value is equal to 100 when the test and reference profiles are identical and
exponentially decreases as the two profiles become less similar.
22. Difference factor Similarity factor Inference
0 100 Dissolution profiles
are similar .
Less than or equal to
15
More than or equal to
50
Similarity or
equivalence of two
profiles.
Limits for similarity and difference factor
23. ADVANTAGE OF THE SIMILARITY AND
DISSIMILARITY FACTORS
Advantage
• They are easy to compute
• They provide a single number to describe the
comparison of the dissolution profiles.
Disadvantage
• The values of the F1 and F2 are sensitive to the
number of the dissolution time point used .
• The basis of the criteria for deciding the difference or
similarity of the dissolution profiles is unclear.
24. CRITERIA FOR EXEMPTIONS
FROM F2 COMPARISONS
• When the API is highly soluble across the physiologically relevant range of pH
and the dosage form exhibits very rapid dissolution. It may not be necessary
to compare dissolution profiles.
• The definition of “very rapid dissolution” varies according to country
regulatory guidance as shown in Table below
25. MINIMUM NUMBER OF TIME
POINTS• A minimum of three time points (zero excluded) is generally required for the
calculation of f2 value.
• The selected time points must be the same for the test and reference
products.
• It should be noted that more than three time points may be required to
adequately characterize the shape of the dissolution profiles.
• The EMA guideline suggests that sampling should occur at least every 15 min
for immediate-release products and that more frequent sampling is
recommended during the period of greatest change in the dissolution profile.
• Therefore, it may be necessary to perform some preliminary studies to
determine the most appropriate time points to be used with each dissolution
medium during the definitive studies with the test and reference batches.
26. The similarities and differences in the minimum number of time points required
for f2 calculation are summarized in Table III.
27. IMPORTANCE OF THE SELECTION OF
THE TIME POINTS
The importance of time point selection to avoid biasing the f2 results is illustrated in
the example dataset provided in Table , which was adapted from a workshop given by
the World Health Organization (WHO) .
28. COEFFICIENT OF VARIATION CRITERIA
• In general, the guidelines for immediate-release products state that the coefficient of
variation (%CV) for the individual dissolution results should be not more than 20%
at the earlier time points and not more than 10% at other time points.
• Time points up to several hours could be considered as “early” time points for an
extended-release dosage form, while 15 min might be a reasonable cut-off for an
immediate-release dosage form.
29. • The global requirements related to variability are provided in Table
31. CONCLUSION
• Graphical method is the first step to compare the dissolution
profiles and it is easy to implement but it is difficult to draw a
conclusion from this.
• Various model dependent methods are used to compare the
dissolution profile but selecting the model , interpretation of the
parameters of the models and the setting the limits of the
similarity is difficult.
• F1 and F2 comparison is very easy and this is most widely
method to compare the dissolution profiles . This is also
recommended by FDA.