QUALITY CONTROL OF TABLETS IPQC stands for in process quality control. These are checks that are carried out before the manufacturing process is completed.
FORMULATION FACTORS EFFECTING BIOAVAILABILITY OF DRUGSN Anusha
Bioavailability means the rate and extent to which the active ingredient is absorbed from a drug product and becomes available at the site of action.
When the drug is given orally, only part of the administered dose appears in the plasma.
By plotting plasma concentrations of the drug versus time, one can measure the area under the curve (AUC).
This curve reflects the extent of absorption of the drug.
Dissolution is mass transfer process.
Dissolution is mainly depend on aqueous solubility of drug.
It is process in which solid mass transfer in liquid medium.
Dissolution based on four process – 1. wetting 2. solubility 3. Swelling 4. diffusion.
Particle size, shape, surface area is important factor can affect the rate of dissolution of drug.
The aqueous solubility is increases, increases rate of dissolution drug
SOLID DISPERSION
Definition: The technology is the science of dispersing one or more active ingredients in an inert matrix in the solid stage.
Need of solid dispersion:
Increases Oral bioavailability of a drug
Increased dissolution rate.
Enhanced release of drugs from ointment.
Improved the solubility & stability.
The concept of solid dispersion was originally proposed by Sekiguchi & obi.
Increasing the dissolution, absorption & therapeutic efficacy of drugs in dosage forms.
Increasing solubility in water.
Improving the oral absorption and bioavailability of BCS Class II drugs.
FORMULATION FACTORS EFFECTING BIOAVAILABILITY OF DRUGSN Anusha
Bioavailability means the rate and extent to which the active ingredient is absorbed from a drug product and becomes available at the site of action.
When the drug is given orally, only part of the administered dose appears in the plasma.
By plotting plasma concentrations of the drug versus time, one can measure the area under the curve (AUC).
This curve reflects the extent of absorption of the drug.
Dissolution is mass transfer process.
Dissolution is mainly depend on aqueous solubility of drug.
It is process in which solid mass transfer in liquid medium.
Dissolution based on four process – 1. wetting 2. solubility 3. Swelling 4. diffusion.
Particle size, shape, surface area is important factor can affect the rate of dissolution of drug.
The aqueous solubility is increases, increases rate of dissolution drug
SOLID DISPERSION
Definition: The technology is the science of dispersing one or more active ingredients in an inert matrix in the solid stage.
Need of solid dispersion:
Increases Oral bioavailability of a drug
Increased dissolution rate.
Enhanced release of drugs from ointment.
Improved the solubility & stability.
The concept of solid dispersion was originally proposed by Sekiguchi & obi.
Increasing the dissolution, absorption & therapeutic efficacy of drugs in dosage forms.
Increasing solubility in water.
Improving the oral absorption and bioavailability of BCS Class II drugs.
WHAT IS COMPRESSION ?
Compression means reduction of bulk volume of material as a result of the removal of gaseous phase (air) by applied pressure
WHAT IS CONSOLIDATION?
Consolidation is an increase in mechanical strength of material resulting from particle - particle interactions.
Presentation about dissolution apparatus testing machine for tablet and new version which is manufactured by lab 8 "Industrial Pharmacy Course" faculty of pharmacy october 6 university.
we added new modification which is already applied and others not applied due to high cost but suggested.
and all modifications are approved from industrial pharmacy department O6U.
WHAT IS COMPRESSION ?
Compression means reduction of bulk volume of material as a result of the removal of gaseous phase (air) by applied pressure
WHAT IS CONSOLIDATION?
Consolidation is an increase in mechanical strength of material resulting from particle - particle interactions.
Presentation about dissolution apparatus testing machine for tablet and new version which is manufactured by lab 8 "Industrial Pharmacy Course" faculty of pharmacy october 6 university.
we added new modification which is already applied and others not applied due to high cost but suggested.
and all modifications are approved from industrial pharmacy department O6U.
In Process Quality Control System (IPQC) for Solid Dosages Form (Tablets)Gaurav kumar
This presentation pertains to the in-process tests performed during the manufacturing process of the solid dosages form (tablets).
The presentation covers the methods and the permissible limits for the tests performed.
These tests are of great importance as these not only ensure quality product but also upholds the cGMP.
Everyone requires a product of the best quality, be it in case of medicines or any other edibles or services. Hence, the presentation deals with the quality control of tablets
Quality control (QC) is a procedure or set of procedures intended to ensure that a manufactured product or performed service adheres to a defined set of quality criteria or meets the requirements of the client or customer. In a pharmaceutical organization a quality control deals with testing, sampling, specification, and documentation, release procedure which ensure that all tests are actually carried out prior to release of material for sale or use. There are several types of hormonal product in different dosage form. These hormonal product quality control and maintaining lies on their specific dosage system. The achievement of these test for hormonal product provides a significant challenge to ingenuity and creativity of hormonal scientist and technologist.
Similar to An orientation lecture For M.Pharm (20)
Compression : It is reduction in bulk volume of the material as a result of displacement of gaseous phase (entrapped air). When external force is applied to powder mass there is reduction in bulk volume. The onset of loading is associated with closed repacking of a powder mass followed by deformation.
Sustained Released Ophthalmic FormulationMcpl Moshi
Dr. V. S. Kashikar
Ophthalmic drug delivery is one of the most challenging endeavor facing the pharmaceutical scientists. The anatomy, physiology and biochemistry of the eye render this organ highly impervious to foreign substance.
Rapid and efficient drainage by the nasolacrimal apparatus, noncorneal absorption and the relative impermeability of the cornea to both hydrophilic and hydrophobic molecules, all account for such poor ocular bioavailability. Thus to increase the ocular bioavailability of drug, we need to increase the ocular residence time of the drug.
Quality audit is defined as a systematic and independent examination to determine whether activities and related results comply with planned arrangements and whether these arrangements are implemented effectively and are suitable to achieve objectives Quality audit means a systematic examination of a quality system
Quality audits are typically performed at defined intervals
.Definition
Objectives
Difference between Quality audit and Periodic evaluation
Self inspection
Types of Quality Audit
Role OF GMP Audit in QA and QC programmes
Elements of a Systemic Audit program
Dr. V. S. Kashikar
Career Guidance to First Year B. Pharm studentsMcpl Moshi
Career Guidance to First Year B. Pharm students
Induction Program
More recently, pharmacists have been faced with increasing health demands which change their direction and focus to PATIENTS instead of the Product.
Bioavailability and bioequivalence studyMcpl Moshi
BCS is a scientific framework for classifying drug substances based on their aqueous solubility and intestinal permeability.
It is a drug development tool that allows estimation of solubility, dissolution and intestinal permeability affect that oral drug absorption.
Kashikar V S
PES Modern College of Pharmacy ( for ladies), Moshi Pune
Bioavailability and Bioequivalence studyMcpl Moshi
Bioavailability and Bioequivalence study, BCS is a scientific framework for classifying drug substances based on their aqueous solubility and intestinal permeability.
It is a drug development tool that allows estimation of solubility, dissolution and intestinal permeability affect that oral drug absorption.
CRISPR-Cas9, a revolutionary gene-editing tool, holds immense potential to reshape medicine, agriculture, and our understanding of life. But like any powerful tool, it comes with ethical considerations.
Unveiling CRISPR: This naturally occurring bacterial defense system (crRNA & Cas9 protein) fights viruses. Scientists repurposed it for precise gene editing (correction, deletion, insertion) by targeting specific DNA sequences.
The Promise: CRISPR offers exciting possibilities:
Gene Therapy: Correcting genetic diseases like cystic fibrosis.
Agriculture: Engineering crops resistant to pests and harsh environments.
Research: Studying gene function to unlock new knowledge.
The Peril: Ethical concerns demand attention:
Off-target Effects: Unintended DNA edits can have unforeseen consequences.
Eugenics: Misusing CRISPR for designer babies raises social and ethical questions.
Equity: High costs could limit access to this potentially life-saving technology.
The Path Forward: Responsible development is crucial:
International Collaboration: Clear guidelines are needed for research and human trials.
Public Education: Open discussions ensure informed decisions about CRISPR.
Prioritize Safety and Ethics: Safety and ethical principles must be paramount.
CRISPR offers a powerful tool for a better future, but responsible development and addressing ethical concerns are essential. By prioritizing safety, fostering open dialogue, and ensuring equitable access, we can harness CRISPR's power for the benefit of all. (2998 characters)
The Importance of Community Nursing Care.pdfAD Healthcare
NDIS and Community 24/7 Nursing Care is a specific type of support that may be provided under the NDIS for individuals with complex medical needs who require ongoing nursing care in a community setting, such as their home or a supported accommodation facility.
Leading the Way in Nephrology: Dr. David Greene's Work with Stem Cells for Ki...Dr. David Greene Arizona
As we watch Dr. Greene's continued efforts and research in Arizona, it's clear that stem cell therapy holds a promising key to unlocking new doors in the treatment of kidney disease. With each study and trial, we step closer to a world where kidney disease is no longer a life sentence but a treatable condition, thanks to pioneers like Dr. David Greene.
Antibiotic Stewardship by Anushri Srivastava.pptxAnushriSrivastav
Stewardship is the act of taking good care of something.
Antimicrobial stewardship is a coordinated program that promotes the appropriate use of antimicrobials (including antibiotics), improves patient outcomes, reduces microbial resistance, and decreases the spread of infections caused by multidrug-resistant organisms.
WHO launched the Global Antimicrobial Resistance and Use Surveillance System (GLASS) in 2015 to fill knowledge gaps and inform strategies at all levels.
ACCORDING TO apic.org,
Antimicrobial stewardship is a coordinated program that promotes the appropriate use of antimicrobials (including antibiotics), improves patient outcomes, reduces microbial resistance, and decreases the spread of infections caused by multidrug-resistant organisms.
ACCORDING TO pewtrusts.org,
Antibiotic stewardship refers to efforts in doctors’ offices, hospitals, long term care facilities, and other health care settings to ensure that antibiotics are used only when necessary and appropriate
According to WHO,
Antimicrobial stewardship is a systematic approach to educate and support health care professionals to follow evidence-based guidelines for prescribing and administering antimicrobials
In 1996, John McGowan and Dale Gerding first applied the term antimicrobial stewardship, where they suggested a causal association between antimicrobial agent use and resistance. They also focused on the urgency of large-scale controlled trials of antimicrobial-use regulation employing sophisticated epidemiologic methods, molecular typing, and precise resistance mechanism analysis.
Antimicrobial Stewardship(AMS) refers to the optimal selection, dosing, and duration of antimicrobial treatment resulting in the best clinical outcome with minimal side effects to the patients and minimal impact on subsequent resistance.
According to the 2019 report, in the US, more than 2.8 million antibiotic-resistant infections occur each year, and more than 35000 people die. In addition to this, it also mentioned that 223,900 cases of Clostridoides difficile occurred in 2017, of which 12800 people died. The report did not include viruses or parasites
VISION
Being proactive
Supporting optimal animal and human health
Exploring ways to reduce overall use of antimicrobials
Using the drugs that prevent and treat disease by killing microscopic organisms in a responsible way
GOAL
to prevent the generation and spread of antimicrobial resistance (AMR). Doing so will preserve the effectiveness of these drugs in animals and humans for years to come.
being to preserve human and animal health and the effectiveness of antimicrobial medications.
to implement a multidisciplinary approach in assembling a stewardship team to include an infectious disease physician, a clinical pharmacist with infectious diseases training, infection preventionist, and a close collaboration with the staff in the clinical microbiology laboratory
to prevent antimicrobial overuse, misuse and abuse.
to minimize the developme
How many patients does case series should have In comparison to case reports.pdfpubrica101
Pubrica’s team of researchers and writers create scientific and medical research articles, which may be important resources for authors and practitioners. Pubrica medical writers assist you in creating and revising the introduction by alerting the reader to gaps in the chosen study subject. Our professionals understand the order in which the hypothesis topic is followed by the broad subject, the issue, and the backdrop.
https://pubrica.com/academy/case-study-or-series/how-many-patients-does-case-series-should-have-in-comparison-to-case-reports/
Global launch of the Healthy Ageing and Prevention Index 2nd wave – alongside...ILC- UK
The Healthy Ageing and Prevention Index is an online tool created by ILC that ranks countries on six metrics including, life span, health span, work span, income, environmental performance, and happiness. The Index helps us understand how well countries have adapted to longevity and inform decision makers on what must be done to maximise the economic benefits that comes with living well for longer.
Alongside the 77th World Health Assembly in Geneva on 28 May 2024, we launched the second version of our Index, allowing us to track progress and give new insights into what needs to be done to keep populations healthier for longer.
The speakers included:
Professor Orazio Schillaci, Minister of Health, Italy
Dr Hans Groth, Chairman of the Board, World Demographic & Ageing Forum
Professor Ilona Kickbusch, Founder and Chair, Global Health Centre, Geneva Graduate Institute and co-chair, World Health Summit Council
Dr Natasha Azzopardi Muscat, Director, Country Health Policies and Systems Division, World Health Organisation EURO
Dr Marta Lomazzi, Executive Manager, World Federation of Public Health Associations
Dr Shyam Bishen, Head, Centre for Health and Healthcare and Member of the Executive Committee, World Economic Forum
Dr Karin Tegmark Wisell, Director General, Public Health Agency of Sweden
Contact ME {89011**83002} Haridwar ℂall Girls By Full Service Call Girl In Ha...
An orientation lecture For M.Pharm
1. QUALITY CONTROL OF TABLETS
Dr. V. S. Kashikar
Asso. Prof., Head, Dept. of Pharmaceutics
PES Modern College of Pharmacy ( for ladies), Moshi Pune 412 105
An orientation lecture
For
M.Pharm
on
2. In Process Quality Control
The development of a drug product is a lengthy process involving drug discovery, laboratory testing,
animal studies, clinical trials and regulatory registration.
To further enhance the effectiveness and safety of the drug product after approval, many regulatory
agencies such as the United States Food and Drug Administration (FDA) also require that the drug product
be tested for its identity, strength, quality, purity and stability before it can be released for use.
For this reason, pharmaceutical validation and process controls are important in spite of the problems
that may been countered. Process controls include raw materials inspection, in-process controls and target
so for final product.
IPQC stands for in process quality control. These are checks that are carried out before the
manufacturing process is completed.
The function of in-process controls is monitoring and if necessary adaption of the manufacturing
process in order to comply with the specifications. This may include control of equipment and environment
too.
15 September 2019 2
3. IPQC/Quality Control-Tablets
DIAMETER AND SHAPE
TABLET THICKNESS
UNIQUE IDENTIFICATION MARKINGS (embossing, engraving
or printing)
HARDNESS (CRUSHING STRENGTH)
FRIABILITY TEST
DISINTEGRATION TEST
WEIGHT VARIATION TEST
DRUG CONTENT
DISSOLUTION
15 September 2019 3
4. Diameter and shape depend on the die and punches selected for the compression of the tablet.
Tablet thickness should be controlled within a ± 5 % variation of standard value.
Tablet thickness is the only dimensional variable related to the compression process and can be
measured by micrometer
HARDNESS (CRUSHING STRENGTH) is a function of the die fill and compression force
FRIABILITY TEST To study the effect of abrasion and shock during handling, packaging and
shipping operations
DISINTEGRATION TEST is a measure of the time required for a tablet to break up into particles
under a given set of conditions
WEIGHT VARIATION test would be a satisfactory method of determining the drug content
uniformity of tablets if the active ingredient is 90 to 95% of the total tablet weight.
DRUG CONTENT The potency (drug content) of tablet is expressed in terms of gm, mg, or mcg
(for some potent drugs) of drug per tablet and is given as the label strength of the product
15 September 2019 4
5. WEIGHT VARIATION
Weigh individually 20 units selected at random and calculate the average weight. Not
more than two of the individual weights deviates from the average weight by more than
the percentage given in the pharmacopea and none deviates by more than twice that
percentage.
15 September 2019 5
IP/BP Limit USP
<80 mg ± 10% <130mg
80 mg to 250 mg ± 7.5% 130 mg to 324 mg
>250 mg ± 5% >324 mg
6. Friability Test As per USP
Friability is the phenomenon where the surface of the tablet is damage or shown a site of damage due to
mechanical shock.
PURPOSE : to evaluate the ability of the tablets to withstand the breakage during the transportation and
handling.
APPARATUS: ROCHE FRIABALITOR
CRITERIA :
For the tablet with a unit equal to or less than 650 mg, take a sample of whole tablets corresponding
as near as possible to 6.5 gm.
For tablets with a unit weight of more than 650 mg, take a sample of 10 whole tablets.
Friability = ((W1-W2)/W1) *100
Compress tablet that lose less than 0.5 to 1.0 % of the Tablet weight are consider acceptable.
15 September 2019 6
7. DRUG CONTENT
This test is applicable to tablets that contain less than 10 mg or less than 10% w/w of active
ingredient. For tablets containing more than one active ingredient carry out the test for each
active ingredient that corresponds to the aforementioned conditions. The test for Uniformity of
content is not applicable to tablets containing multivitamins and trace elements.
Determine the content (assay) of active ingredient(s) in each of 10 tablets/30 tablets.
Comply with the test if not more than one (9 out of 10) of the individual values thus obtained
is outside the limits 85 to 115 % of the labeled drug content and none is outside the limits 75
to 125 % of the labeled drug content. If these conditions are not met repeat the determination
using remaining 20 tablets. The tablets comply with the test if in the total sample of 30 tablets,
none is outside the limits 85 to 115 % range.
Note: Several samples of tablets should be taken from the various part of production run to satisfy
statistical procedure.
15 September 2019 7
9. Sr.
No
Types of tablets Medium Temperature Limit
1 Uncoated Water/As specified in
monograph
37º± 2ºC Within 30 min/As per individual
monograph
2 Coated Water/As specified in
monograph
37º± 2ºC Within 30 min/ As per individual
monograph
3 Enteric-coated Tablets Simulated gastric fluid,
Simulated intestinal fluid
37º± 2ºC 01 hour in simulated gastric fluid : No
disintegration
As per individual monograph:
Simulated intestinal fluid should
disintegrate within 2 hour
4 Buccal Tablet Water/As specified in
monograph
37º± 2ºC Within 4 hour
Disintegration Testing Condition (USP)
15 September 2019 9
10. Sr.N
o
Types of tablets Medium Temperature Limit
1 Uncoated Water/ Buffer 37º± 2ºC Within 15 min/ As per individual
monograph
2 Film Coated Water 37º± 2ºC Within 30 min/ As per individual
monograph
3 Sugar coated Water/ 0.1N HCl 37º± 2ºC Within 60 min/ As per individual
monograph
4 Dispersible Tablets Water 20º± 5ºC Within 03 min/ As per individual
monograph
5 Effervescent Tablets Water 20º± 5ºC Within 05 min/ As per individual
monograph
6 Enteric-coated Tablet 0.1N HCl
Mixed phosphate
buffer pH 6.8
37º± 2ºC 02 hour in HCl: No disintegration
60 min in Buffer: Disintegrate
7 Soluble Tablet Water 20º± 5ºC Within 03 min.
Disintegration Testing Condition (IP)
15 September 2019 10
11. Dissolution Test
When solid particles come in contact with the GI tract, a
saturated layer of drug solution is created very quickly in
the surface of particles in the liquid immediately
surrounding them (called the diffusion layer). The drug
molecules then diffuse through the GI content to the
lipoidal membrane where diffusion across the gastro
intestinal membrane and absorption into the circulation
takes place.
15 September 2019 11
12. There are two possible scenarios for the drug dissolution
• Absorption from solution takes place following the rapid dissolution of
solid particles. In this case rate of absorption is controlled by rate of
diffusion (Rate limiting step) into the GI fluid.
• Absorption from solution takes place following the slow dissolution of
solid particles. In this case rate of absorption is controlled by rate of
dissolution (Rate limiting step) into the GI fluid.
Hence, Dissolution is a process in which a solid substance solubilises in a
given solvent i.e., mass transfer from solid surface to the liquid phase
15 September 2019 12
13. In the pharmaceutical industry, drug dissolution testing is routinely
used to provide critical in vitro drug release information for
both quality control purposes, i.e., to assess batch-to-batch
consistency of solid oral dosage forms such as tablets and drug
development, i.e., to predict in vivo drug release profiles.
The main objective of developing and evaluating an IVIVC is to
establish the dissolution test as a surrogate for human studies, as
stated by the Food and Drug Administration (FDA).
15 September 2019 13
14. Dissolution test is conducted for,
Optimization of therapeutic effectiveness during product
development and stability assessment.
Routine assessment of production quality to ensure uniformity
between production lots.
Assessment of ‘bioequivalence’.
Prediction of in-vivo availability, i.e. bioavailability (where
applicable).
15 September 2019 14
16. USP
Apparatus Type
NAME Rotator Speed Used for
I Rotating basket 50-120 rpm Immediate release, delayed release, chewable tablets,
delayed release suppositories, Extended release tablets
and floating dosage form
II Paddle 25-50 rpm Immediate release, orally disintegrating tablets, chewable
tablets, delayed release and Extended release tablets and
capsules and suspensions.
III Reciprocating cylinder
It enables the product to be
subjected to different dissolution
media and agitation speeds in a
single run
6-35 rpm Controlled release formulations, Chewable tablets and
beads
IV Flow through cell
To provide Sink conditions by
continually removing solvent and
replacing it with fresh solvent
- Drug products containing poorly soluble API, Powders
and granules, microparticles and Implants.
V Paddle over disk 25-50 rpm Transdermal Patches, Ointments and Emulsions
VI Rotating Cylinder
Basket being replaced by a stainless
steel cylinder
25-50 rpm Transdermal Patches
VII Reciprocating Holder
A sample holder that oscillates
up and down
30 rpm Controlled release formulations Transdedrmal
formulations & non disintegrating oral formulations
15 September 2019 16
21. Model Linear Equation Plot System that
follows the
model
On X- axis On Y-axis
Zero Order Qt = Qo +Kot Time Cumulative of
percentage of
drug release
Osmotic systems,
transdermal
system
First Order Log C = log Co – Kt /
2.303
Time Log cumulative
percentage of
drug remaining
Water soluble
drugs in a
porous matrix
Higuchi Model Qt = KHt1/2 Square root of
Time
Cumulative
percent amount of
drug release
Diffusion matrix
formulation
Hixon Crowell Wo1/3 – Wt1/3 = Kst Time Cube root of
percentage of
drug remaining
Erodible matrix
formulation
Korsmeyer-
peppas Model
Mt/Ma = Ktn Log Time Log cumulative
percentage of
drug release
Swellable
polymeric
devices
Some model with linear equation for graphical presentation
15 September 2019 21
22. Where, a = Scale parameter
b = Suface parameter
Qt = Fraction of dose released at time t
K,KH,K0,KS = Release rate constant characteristics to respective models
m & n = Release exponents
Mt = Amount released at time t
M∞ = Amount release at infinite time
Q0 = Drug amounts remaining to be released at zero hour
Qt = Drug amounts remaining to be released at time t
Ti = Lag time before the onset of dissolution
W0 = Initial amount of drug present in matrix
Wt = Amount of drug released at time t
15 September 2019 22
23. Korsmeyer-peppas Model
A plot of the log (cumulative percentage drug released ) vs log (time) yields
slope n (diffusion exponent) having value.
n = 0.5 indicating pure fickian diffusion.
n = 0.5-1 or n = 0.45-0.89 indicating anomalous non- fickian diffusion i.e
the rates of solvent penetration and drug release are in the same range. This deviation is
due to increased drug diffusivity from the matrix by the solvent induced relaxation of the
polymers.
n=0.89 or n = 1 indicate zero order release which can be achieved when drug
diffusion is rapid compared to the constant rate of solvent induced relaxation and
swelling in the polymer (case II transport for swellable polymers).
15 September 2019 23
29. First Step
Determine concentration of drug released by using formula
Y =mX +/- C
Y is absorbance, m is slope, C is intercept, X is concentration (mcg/ml)
Second Step
Calculate amount of drug released
Amount of drug released (mg)= [Concentration X Dilution factor X Volume of Dissolution
medium] / 1000
Final Step
% Drug release = Amt of drug released (mg) X 100 / Dose (mg)
Cumulative % drug Released (CDR) =
Volume of sample withdrawn(ml)/Bath volume (v) X P (t-1) +Pt
Where, Pt Percentage drug released at time t
P (t-1) = Percentage drug released previous to t
15 September 2019 29
31. BIOWAIVER
Biowaiver is an exemption granted by the US FDA to conduct in-vivo bioequivalence studies. It
implies that it is not necessary for generic products to conduct the in-vivo studies for product
approval. Instead a dissolution test can be adopted.
Biowaiver can be suggested only for solid, orally administered immediate release products (85%
release in 30 min), containing highly soluble drugs over a pH range of 1 to 7.5.
For a bioequivalence study of a waiver, the test and reference product should exhibit similar
dissolution profile (f2 >50). However, it is not applicable for buccal, sublingual, oral dispersion
and modified release formulations. Biowaiver reduces the cost of bringing new products to the
market. It has a major advantage in reducing the time for approval of a product.
15 September 2019 31
32. Fit factor:
Similarity factor f2: For comparison of in-vitro dissolution profiles, similarity and
difference factors are emphasized by US FDA. As the name specifies, similarity
factor (f2) stresses on the comparison of closeness of two comparative
formulations. The f2 parameter is commonly used to establish similarity of two
dissolution profiles The FDA defines Similarity factor as " the logarithmic
reciprocal square root transformation of one plus the mean squared (the average
sum of squares) differences of drug percent dissolved between the test and the
reference products".
f2 = 50 + log {[1+ (1/n) ∑t=1 * n (Rt-Tt) 2] -0.5 ×100}
Rt and Tt are the cumulative percentage dissolved at each of the selected n time points of the reference and test product
respectively
Two profiles are considered to be same when f2=100. f2 value results in 50 at an average difference of
10% for all measured time points. f2 value between 50-100 indicates similarity between two
dissolution profiles. In other words if difference at each sampling time is less than or equal to 10% f2
value will be between 50 and 100.
15 September 2019 32
33. Dissimilarity factor (f1):
Dissimilarity factor focuses on the difference in percent
dissolved between reference and test at various time intervals.
Therefore the factors directly compare the difference between
percent drug dissolved per unit time for a test and a reference
product. f1 factor is used to calculate the approximate % error
in drug release profile.
f1 should be between 0 and 15.
f1= {[Σ t=1 n |Rt-Tt|] / [Σ t=1 nRt]} ×100.
15 September 2019 33
34. The criteria stated by US FDA for dissolution profile
1. The dissolution profiles can be compared only when the number of dissolution unit used is equal to or greater
than 12. f2 should be computed from average mean dissolution data of 12 units.
2. For accurate calculation of similarity factor, statistical approach of establishment of confidence intervals to
determine whether the reference and test are statistically significant or not may be used.
3. The dissolution conditions should be identical for both reference and test products like the strength of dosage
form, test time intervals, temperature, rpm, total test time etc.
4. The literature also states to consider only one time after 85% dissolution of product, since f2 values are
sensitive to number of dissolution time points.
5. For rapid dissolving products, that may dissolve 85% in 15 minutes, comparison of dissolution profiles is not
mandatory.
6. Similarity factor of 50-100 ensures sameness of two products.
7. Difference factor of 0-15 ensures minor difference between two products.
Therefore prior to in-vivo study, comparison of in-vitro dissolution profiles using fit factors may be the promising
surrogate.
15 September 2019 34