This document discusses stability studies and drug kinetics. It defines stability as how a product maintains its quality over time. Stability testing is used to determine shelf life, recommended storage conditions, and container suitability. Kinetics deals with the rates of chemical reactions and processes. The order of a reaction determines how concentration influences the reaction rate. Common orders seen in drug degradation are zero order (rate is constant), first order (rate depends on concentration of one reactant), and second order (rate depends on concentrations of two reactants). Understanding reaction kinetics helps predict degradation over time and ensure drug quality.
QUALIFICATION OF UV-VISIBLE SPECTROPHOTOMETER, FTIR, DSC, HPLCAnupriyaNR
Analytical method qualification consists of a simplified evaluation of a subset of validation characteristics with a goal to demonstrate that an analytical method is scientifically sound and suitable for its intended use. In contrast to validation, analytical method qualification is performed without predefined acceptability criteria. Qualification may be performed as a prerequisite to method validation, or when an assay for product knowledge has not yet been established as a test for a critical product quality attribute. Qualification of equipment is pre-requisite for validation of the process in which the equipment is being used. Many types of equipment have measuring devices on them. Calibration of measuring devices is a part of qualification. Calibration of measuring devices is important, as the data is often collected through them. If the data collected is not from measuring devices that have been calibrated, the data cannot be relied upon. Thus the whole validation exercise can be questioned.
Dissolution, factors affecting drug dissolution, methods to evaluate dissolution, advantages and disadvantages, recent approaches--these are the topics covered in this presentation.
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.
QUALIFICATION OF UV-VISIBLE SPECTROPHOTOMETER, FTIR, DSC, HPLCAnupriyaNR
Analytical method qualification consists of a simplified evaluation of a subset of validation characteristics with a goal to demonstrate that an analytical method is scientifically sound and suitable for its intended use. In contrast to validation, analytical method qualification is performed without predefined acceptability criteria. Qualification may be performed as a prerequisite to method validation, or when an assay for product knowledge has not yet been established as a test for a critical product quality attribute. Qualification of equipment is pre-requisite for validation of the process in which the equipment is being used. Many types of equipment have measuring devices on them. Calibration of measuring devices is a part of qualification. Calibration of measuring devices is important, as the data is often collected through them. If the data collected is not from measuring devices that have been calibrated, the data cannot be relied upon. Thus the whole validation exercise can be questioned.
Dissolution, factors affecting drug dissolution, methods to evaluate dissolution, advantages and disadvantages, recent approaches--these are the topics covered in this presentation.
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.
vendor validation is important now a days in pharmaceutical industries.
vendor is authorizes seller of raw material,equipment and packaging material to the pharmaceutical organization.
Presentation on-stability-study of pharmaceutical productMd Mohsin
this content takes important information about stability & stability study of pharmaceutical products including guidelines,climate zone,testing conditions,sampling plan,extension of shelf life,re test,current trends in stability study etc.
The system to deliver the drug to the body to produced desired therapeutic action and activity against diseases and disorders is known as Drug delivery system
Chapter of M pharm First semester, Which covers order and rate of reaction,first order and zero order kinetics , ICH guidelines for stability testing,Storage conditions,etc.
The all the content in this profile is completed by the teachers, students as well as other health care peoples.
thank you, all the respected peoples, for giving the information to complete this presentation.
this information is free to use by anyone.
KINETICS OF STABILITY , ACCELERATED STABILITY STUDY, AND ICH STABILITY GUIDEL...Akhila Anil
CHEMICAL KINETICS
ORDER OF REACTION
DETERMINATION OF ORDER
SALIENT FEATURES OF ACCELERATED DRUG STABILITY
STABILITY METHOD
LIMITATIONS OF ACCELERATED DRUG STABILITY
ICH GUIDELINES ON STABILITY
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
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.
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
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!
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
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
- 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
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists
Stability studies
1. STABILITY STUDIES
……… A measure of how a pharmaceutical product
maintains its quality attributes over time
Dr. Gajanan S. Sanap M.Pharm.,Ph.D
Department of Pharmaceutics
Ideal College of Pharmacy and Research
Kalyan 421- 306
2. STABILITY –
The capacity of a drug or product to remain within established
specifications of identity , quality, purity in a specific period of time.
OR
The capacity or the capability of a particular formulation in a specific
container to remain with in particular chemical , microbiological ,
therapeutically , and toxicological specifications.
OR
USP defines stability of pharmaceutical product as , “extent to which a
product retains with in specified limits and throughout its period of
storage and use ( i.e. shelf life).
3. Stability testing is used to:
Provide evidence as to how the quality of the drug product varies with
time.
Establish shelf life for the drug product.
Determine recommended storage conditions.
Determine container closure system suitability.
Why Stability studies are necessary ?
Chemical degradation of the product leads to lowering of the concentration
of the drug in the dosage form.
Toxic products may be formed , due to chemical degradation of the active
ingredient.
Advantages of Stability studies
Assurance to the patient Economic considerations Legal requirement
4. OBJECTIVES
1. To determine maximum expiration date/ shelf life.
2. To provide better storage condition.
3. To determine the packaging components.
4. To gather information during preformulation stage to
produce a stable product.
5. Study Storage condition Minimum time
period covered by
data at submission
Long Term
(Ambient)
25º C ± 2º C
60%RH ± 5%
12 months
Intermediate
(controlled)
30º C ± 2º C
60%RH ± 5%
6 months
Accelerated 40º C ± 2º C
75%RH ± 5%
6 months
7. It involves the study of rate of change and the way in which this rate is
influenced by the concentration of reactants, products, and other
chemical species that may be present, and by factors such as solvents,
pressure, and temperature.
Kinetics applies to:
Stability
Incompatibility,
Dissolution,
Absorption,
Distribution
Drug action at molecular level
Elimination processes
8. WHY DO WE STUDY ABOUT KINETICS?
It gives an in light into the mechanism of changes involved
Allows a prediction of the degree of change that will occur
after a given time has elapsed.
9. DRUG STABILITY
• The resistance of the drug to the various chemical, physical, and
microbiological reactions that may change the original properties of
the preparations during transport, storage and use.
• Quantitatively it is expressed as shelf life.
Shelf life
is the time during which the medicinal product is predicted to
remain fit for its intended use under specified conditions of storage.
It is the time from manufacture or preparation until the original
potency or content of the active ingredient has been reduced by 10%
[t10 or t90] which is the limit of chemical degradation
10. WHY DO WE STUDY ABOUT DRUG STABILITY?
Safety of the patient [toxic products or less potent product]
Legal requirements with identity, strength, purity and quality
To prevent economic repercussions.
11. RATES AND ORDERS OF REACTIONS
RATES
• the speed or velocity of a reaction with which a reactant or
reactants undergoes a change.
• It is determined by the change in the concentration of the
reactants or products as a function of time.
• The rate may be determined by the slowest or rate determining
step.
kc
n
Rate
dt
dc
12. ORDERS OF REACTIONS
the number of concentrations that determine rate.
the way in which the concentration of the reactant influences
the rate.
Law of mass action
The rate of a reaction is proportional to the molar concentrations of the reactants each raised to
power equal to the number of molecules undergoing reaction.
a A + b B Product
Rate α [A]a .[B]b
Rate = K [A]a .[B]b
Order of reaction = sum of exponents
Order of A = a and B = b
Then Overall order = a + b
13. Example:
The reaction of acetic anhydride with ethyl
alcohol to form ethyl acetate and water
(CH3 CO)2 + 2 C2H5OH 2 CH3 CO2 C2H5 + H2O
Rate = K [(CH3 CO)2 O] . [C2H5OH]2
Order for (CH3 CO)2 O is 1st order
Order for [C2H5OH]2 is 2nd order
Overall order of reaction is 3rd Order
14. ZERO ORDER REACTIONS
rate is constant and is independent of the concentration of
any of the reactants.
A constant rate of drug release from a dosage form is highly
desirable.
Equation for zero order:
15. Equation for zero order:
a [A] k Product (P)
Rate = - dc/dt = K [c]0
- dc/dt = k dc = - k dt
co = Initial concentration
ct = Concentration at time t
t
t
c
c
kdtdc
t
00
C – C0 = -kt
16. Units of the rate constant K
c = co – Kt
K = co – c /t
K = Concentration / time
= mole / liter . second
= M. sec-1
C
t
17. Determination of t1/2
Let c = co /2 and t1/2 = t
substitute in equation;
c = co – k t
Note: Rate constant (k) and t1/2 depend on co
Determination of t0.9
Let c = 0.9 co and t= t0.9
substitute in equation;
c = co –k t
t1/2 = co / 2K
t90% = t0.9 = 0.1 co / k
18. Examples
• Drug X degrades by a zero-order process with a rate constant
of 0.05 mg ml1 year−1 at room temperature. If a 1%
weight/volume (w/v) solution is prepared and stored at room
temperature:
1. What concentration will remain after 18 months?
2. What is the half-life of the drug?
20. FIRST ORDER REACTION
The most common pharmaceutical reactions
e.g; drug absorption & drug degradation
The reaction rate of change is proportional to drug
concentration.
21. - dc/dt = kc1 = kc
- dc/c = kdt
t
t
t
c
dtk
c
dc
00
ktcc o lnln
303.2
loglog 0
kt
cc
22. C = co e –kt
Difficult to determine slope
lnc = lnco – kt
Slope = c1 – c2 / t1 – t2
Slope = -k
lnco
Log co
Log c = log co – kt / 2.303
Slope = c1 – c2 / t1 – t2
Slope = -k / 2.303
Or use semi log paper
C Lnc
Logc
t t
t
23. Determination of t1/2
Let t = t1/2 and C = C0 /2
substitute in ln C = ln C0 – Kt
t1/2 = ln 2/ K = 0.693 / K
K units = 0.693 / t1/2 = time-1
Determination of t0.9
Let t = t0.9 c = 0.9 Co
substitute in ln c = ln co – Kt
t0.9 = 0.105 / K and K = 0.105/ t0.9
t1/2 = 0.693 / K
t0.9 = 0.105 / K
24. Examples
1 Ten (10) ml aqueous solutions of drug A (10% w/v) and drug B
(25% w/v) are stored in two identical test tubes under
identical storage conditions at 37°C for 3 months. If both
drugs degrade by first-order, which drug will retain the highest
percentage of initial concentration?
(a) Drug A
(b) Drug B
(c) They will be the same.
2. The concentration of drug X in aqueous solution drops by 10%
per month when stored at room temperature. If the
degradation occurs by first order, what concentration will
remain if a 5 mg/ml solution of the drug is stored under the
same conditions for 3 months?
25. 3. A 5 gm/100 ml solution of drug X is stored in a closed test tube
at 25°C. If the rate of degradation of the drug is 0.05 day−1,
calculate the time required for the initial concentration to
drop to (a) 50% (half-life) and (b) 90% (shelf-life) of its initial
value.
4. A 5 gm/100 ml solution of drug X is stored in a closed test tube
at 25°C. If the rate of degradation of the drug is 0.05 day−1,
calculate the time for the drug concentration to degrade to
2.5 mg/ml.
26. PSEUDO ORDER REACTIONS
• For some reactions, the rate of the reaction may be
independent of the concentration of one or more of the
reacting species over a wide range of reactions.
• These may occur under the following conditions:
One or more of the reactants enters into the rate equation
in great excess compared to others;
One of the reactant is catalyst;
One or more of the reactants is constantly replenished
during the course of reaction
27. SECOND ORDER REACTION
Rate depends on the product of two concentration terms.
When you have two components reacting with each other or
one component reacting with itself.
Example: 2HI = H2 + I2 , here the reaction is not simply a
matter of an HI molecule falling apart, but relies on the
collision of two HI molecules.
The rate of reaction from the law of mass action is given by:
Rate = dc/dt = k[HI][HI] = k[HI]2
28. dc/dt = -kc2
dc/c2 = -kdt
t
t
c
c
dtk
c
dc
0
2
0
kt
cc
0
11
2nd Order reaction
29. 2nd order graph
Units of K:
1/C = 1/Co + Kt
K = (1/C - 1/Co) / t
K = M-1. sec -1
i.e, K is dependent on initial drug concentration.
Derive equation for t1/2 and shelf life
Half life: t1/2 = 1 / KCo
Shelf life: t0.9 = 0.11 / KCo
30. DETERMINATION OF ORDER AND RATE CONSTANTS
1. Substitution method [data plotting method]
• Data accumulated in experimental kinetic study may be
substituted in the integrated form of the equation that
describes the various reaction orders and observing which
plot is a straight line.
• Accordingly, plot of:
Concentration against time …….. zero order reaction [if
straight line]
ln concentration against time ……. First order reaction [if
straight line]
1/concentration against time …….. second order reaction
[if straight line].
31. 2.Half-life method
• This method is based on the relationship between the initial
concentration of the reactant, the half life, and the reaction
order.
• For zero-order reactions, t1/2 increases with increasing
concentration, whereas for first-order reactions, t1/2 does not
change with change in concentration
32. DEGRADATIVE PATHWAYS
Degradation of active drug leads to lowering of quantity of the therapeutic
agent in the dosage form.
It may not be extensive , a toxic product formation may take place due to
decomposition instability of drug product can lead to a decrease in its
bioavailability .
Changes in physical appearance of given dosage form may take place.
Degradation may increase or may decrease the potency of drug.
Sometimes active drug may retain its potency , but excipients like –
antimicrobial , preservatives , solubilizers , emulsifying or suspending agent
may degrade , lead to compromising the integrity of drug product.
EXAMPLE :
Drugs like 5-fluorouracil , carbamazipine , digioxin and theophylline have
narrow therapeutic indices these needs to be carefully treated in patient so
that plasma levels are neither too high as to be toxic nor too low as to be
ineffective
The antimicrobial chloroquine can produce toxic reactions that are attribute
to the photochemical degradation of the substance.
33. DEGRADATION MAY BE OF TWO TYPES
PHYSICAL DEGRADATION
CHEMICAL DEGRADATION
1. OXIDATION
2. DECARBOXYLATION
3. PHOTOLYSIS
4. RACEMIZATION
5. HYDROLYSIS
PHYSICAL DEGRADATION
The physical stability properties includes appearance, palatability ,uniformity
,dissolution and suspend ability are retained . Maintained throughout the shelf life
of the drug.
It includes following :
Loss of water
loss of volatile oil
Water Absorbance
Polymorphism
Color change
34. Physical degradation includes following :
LOSS OF VOLATILE CONTENT: Volatile compounds used such as
Alcohol ether , camphor oils , etc . Try to escape from the formulation
leads to degradation of formulation.
Example : nitroglycerine from drugs evaporate.
LOSS OF WATER : Water loss from liquid preparation (o/w emulsion)
leads to changes in stability .It causes crystallization of drug product .which
may lead to increase in potency , and decrease in weight.
Example : water evaporates from Na2SO4 .BORAX.
WATER ABSORBANCE : pharmaceutical formulations which are
hygroscopic in nature absorb the water from its external environment leads
to degradation .
Example : gelatin capsule , deliquescent salts like –Cacl3 , Potassium
citrate.
POLYMORPHISM: A stable crystal form is effected (it may loosen)
leads to the formation of polymorph and cause instability in formulation.
This may lead to alteration in solubility , dissolution of drug
COLOR CHANGE: Loss or development of color may occur . (due to
change in PH , use of reducing agent , exposure to light )
35. Physical Stability
Physical stability implies that:
The formulation is totally unchanged throughout its shelf
life and has not suffered any changes by way of appearance,
organoleptic properties, hardness, brittleness, particle size
etc.
It is significant as it affects:
1.pharmaceutical elegance
2.drug content uniformity
3.drug release rate.
36. Physical Stability
Formulation Likely physical
instability problems
Effects
Oral solutions 1- Loss of flavor
2- Change in taste
3- Presence of off
flavors due to
interaction with plastic
bottle
4- Loss of dye
5- Precipitation
6- discoloration
Change in smell
or feel or taste
37. Formulation Likely physical
instability problems
Effects
Parenteral
solutions
1. Discoloration due to
photo chemical
reaction or oxidation
2. Presence of precipitate
due to interaction
with container or
stopper
3. Presence of “whiskers”
4. Clouds due to:
(i) Chemical changes
(ii) The original
preparation of a
supersaturated
solution
Change in
appearance and in
bio-availability
38. Physical stability
Formulation Likely physical
instability
problems
Effects
Suspensions 1- settling
2- caking
3- crystal
growth
1-Loss of drug
content
uniformity in
different doses
from the bottle
2- loss of
elegance.
39. Physical stability
Formulation Likely physical
instability
problems
Effects
Emulsions 1- Creaming
2- coalescence
1- Loss of drug
content
uniformity in
different doses
from the bottle
2- loss of
elegance
41. Physical stability
Formulation Likely physical
instability
problems
Effects
Semisolids
(Ointments and
suppositories)
1. Changes in:
a) Particle size
b) Consistency
2. Caking or
coalescence
3. Bleeding
1-Loss of drug
content
uniformity
2- loss of
elegance
3-change in
drug release
rate.
42. Physical stability
Formulation Likely physical
instability problems
Effects
Tablets Change in:
a) Disintegration
time
b) Dissolution profile
c) Hardness
d) Appearance (soft
and ugly or
become very
hard)
Change in
drug release
43. CHEMICAL DEGRADATION
Chemical degradation of a dosage form occurs through several pathways
like –hydrolysis , oxidation , decarboxylation , photolysis , racemization.
which may lead to lowering of therapeutic agent in the dosage form,
formation of toxic product , decreased bioavailability etc.
1. HYDROLYSIS
Most important in systems containing water such as emulsion , suspension ,
solutions , etc.
Also for drugs which are affected by moisture (water vapor) from
atmosphere.
It is usually catalysed by hydrogen ion(acid) or hydroxyl ion(base).
In this active drug is decomposed with solvent.
Usually solvent is water some time reaction may involve pharmaceutical
co solvents such as ethyl alcohol or poly ethylene glycol
Main classes of drugs that undergo hydrolysis are the ESTERS ,AMIDE
,ALKALI, ACID.
44. Cont…
ESTER HYDROLYSIS involve acyl – acid cleavage.
Example of drugs: aspirin ,atropine , physostigmine , procaine..
R .COOR (ester) + H2O RCOOH (acid) + HOR(alcohol)
AMIDE HYDROLYSIS is more stable than ester , susceptible to specific and
general acid base hydrolysis. It involves cleavage of amide linkage to give an
amine instead of alcohol as in case of esters.
Example of drugs : chloramphenicol , barbiturates .
RCONHR(amide) + H2 O RCOOH + NH2 R(AMINE)
45. Some functional groups subject to
Hydrolysis
Drug type Examples
Esters Aspirin, alkaloids
Dexmethasne sodium
phosphate
Nitroglycerin
Lactones Pilocarpine
Spironolactone
Amides Chloramphenicol
Imides Glutethimide
Malonic ureas Barbiturates
46. PROTECTION AGAINST OXIDATION
Avoiding contact with moisture at time of manufacture.
Packaging in suitable moisture resistant packs such as strip packs and storage in
controlled humidity and temperature.
In liquid dosage form since , hydrolysis is acid or base catalyzed , an optimum
PH for max stability should be selected and the formulation should be stabilized
at this PH by inclusion of proper buffering agents.
Hydrolysis of certain drugs such as benzocaine and procaine can be decreased
by the addition of specific complexing agent like caffeine to the drug solutions .
Hydrolysis susceptible drugs such as penicillin and derivatives can be prevented
by formulating them in the dry powder form for reconstitution or dispersible
tablets instead of a liquid dosage form such as solutions or suspensions.
47. 2. OXIDATION
Oxidation is controlled by environment i.e, light ,trace elements , oxygen and
oxidizing agent .
Occurs when exposed to atmospheric oxygen.
Either the addition of oxygen or removal of hydrogen .
Oxidation is the loss of electrons while reduction is the gain of electrons.
AUTOXIDATION
The reaction between the compounds and molecular oxygen is required for
initiating the chain reaction is called autoxidation .
Free radicals produced during initial reaction are highly reactive and further
catalyze the reaction produced additional free radicals and causing a chain
reaction.
48. Heavy metals such as copper , iron , cobalt , and nickel have been known to
catalyze the oxidative degradation .Heat and light further influence the kinetics
of oxidative degradation processes.
STEPS INVOLVED OXIDATION REACTION
INITIATION : Formation of free radicals is taken place .
R--H R’ + [H’}
PROPOGATION : here the free radical is regenerated and react with more oxygen .
R’ + O2 R’—O2
R’O2 + RH ROOH + R’
HYDROPEROXIDE DECOMPOSITION
ROOH RO’ + OH’
TERMINATION : free radicals react with each other resulting in inactive products.
R’--O2 + X Inactive product
RO2 + RO2 Inactive product
EXAMPLE OF DRUGS DECOMPOSED BY OXIDATION PATHWAYS
Archis oil , clove oil , ethyl oleate ,Heparin , Ascorbic acid , Morphine ,Vitamin A , Vitamin
B12 , etc.
49. PROTECTION AGAINST OXIDATION
USE OF ANTIOXIDANTS : antioxidants are Mainly of 3 types :
1. The first group probably inhibits the oxidation by reacting with free radicals.
Example – tocopheral , butylated hydroxyl anisole (BHA) , butylated hydroxyl
toluene's (BHT). Concentration 0.001 – 0.1%.
2. The second group comprising the reducing agents , have a lower redox potential
than the drug or other substance that they should protect and are therefore more
readily oxidized.
Example –ascorbic acid and iso ascorbic acid , potassium or sodium salts of
metabisulfite.
3. The third group, little antioxidant effect themselelf but enhance the action of true
antioxidant .example
Example -- Citric acid , tartaric acid , disodium edetate and lecithin .
USE OF CHELATING AGENT
when heavy metals catalyze oxidation .
Example -- EDTA , citric acid , tartaric acid form complexes.
50. 3. PHOTOLYSIS
Exposure to light cause substantial degradation of drug molecule.
• When molecules are exposed to electromagnetic radiation they absorb light
(photons) at characteristic wavelength which cause increase in energy which
can :
Cause decomposition.
Retained or transferred.
Be converted to heat .
Result in light emission at a new wavelength (fluorescence ,
phosphorescence).
• Natural sun light lies in wavelength range (290– 780nm) of which only higher
energy (UV) range (290 --320) cause photo degradation of drugs.
`
51. Example of phototoxic drugs:
Furosemide , acetazolamide , cynocobalamine .
EXAMPLE
Sodium nitropruside in aqueous solution (which is administered by IV infusion
for management of acute hypertension ).
If protected from light it is stable to at least 1yr.
If exposed to normal room light it has a shelf life of 4 hrs.
PROTECTION
Use of amber colored bottles .
Storing the product in dark , packaging in cartons also act as physical barrier to
light.
Coating of tablets with polymer films.
52. Accelerated Stability StudiesAccelerated Stability Studies
Stability study to predict the shelf life of the product, by accelerating
the rate of decomposition, preferably by increasing the temperature of
reaction conditions.
With the advancement in branch of kinetics, shelf life of a dosage form
can be predicted within months based on accelerated stability reports
Preparations are subjected to high stresses during stability testing.
Common high stresses include :
Temperature
Humidity
Light
53. It is defined as the time required for the concentration of the reactant to reduce to
90% of its initial concentration .Represented as t90 and the units of time /conc.
t90 = (a-0.9a) = 0.1 a
ko ko
Where , a = initial concentration .
ko = specific rate constant for zero order reaction.
(the time from the date of manufacture and packaging of the formulation until its
chemical or therapeutic activity is maintained to a predetermined level of labeled
potency and ,
its physical characteristic have not changed appreciably or deleteriously ).
54. Arrhenius equation
It explains the effect of temperature on rate of a reaction.
According to Arrhenius, for every 10º rise in temperature, the speed
of reaction increases about 2-3 times.
k = A e -Ea / RT
Arrhenius factor
Energy of activation
Ideal gas constant
Log k = log A – Ea / 2.303 RT
Arrhenius factor is the frequency of molecular collisions occuring between
the molecules.
55. Estimation of k value
The reaction is conducted at several temperatures.
Concentration of reactants is determined.
Appropriate graphs are drawn for the kinetic data.
Data is processed for all the orders.
The order of the reaction is identified.
From the slopes of the lines, k values are calculated for all
temperatures.
56. Estimation of energy of activation
A graph can be drawn by taking log k on y-axis and reciprocal
temperature (1/T) on x-axis.
A straight line is obtained, the slope of the line is negative and the
magnitude is Ea / 2.303 R.
The intercept corresponds to log A
All the constants in the Arrhenius equation can be obtained from the
graph.
Activation energy is the minimum energy that a molecule should
possess so that the molecular collisions produce the product.
57.
58. The Preparation is stored at different elevated temperatures, to
accelerate the degradation
Samples are withdrawn at different time intervals
The Order of the reaction is determined by plotting the appropriate
function of concentration against time and linear relationship is
determined
Straight line in a graph permits the estimation of k value from the slope
Similarly graphs are drawn for different elevated temperatures.
K value for each temperature are calculated.
By using Arrhenius relationship, Log k values are plotted against
reciprocal of absolute temperature, energy of activation can be
calculated.
Steps involved in prediction of shelf life
59. Extrapolate the straight line to room temperature (k25) or
refrigerated temperature and read the log k value on y-axis.
Substitute the k value in the appropriate equation to get the shelf
life of the product.
60. Arrhenius plot for predicting the rate constant at ambient
temperature(25ºC).
61. Stability
investigation
Organoleptic and
physicochemical
stability
Photostability
Chemical stability
Dosage form
Solid
Semisolid
Liquid
All
Solid
Semisolid
Liquid
Storage condition
Storage in open
container until
equilibrium is reached at
25ºC/60%,30ºC/70%,
40ºC/75%
5ºC
≥ - 10ºC
5ºC -40ºC Temperature
cycle within 24 hrs
40ºC(content uniformity)
5ºC
≥ -10ºC
Xenon lamp
40ºC, 50ºC, 60ºC, 70ºC
30ºC, 40ºC, 50ºC
40ºC, 50ºC, 60ºC, 70ºC
Storage period
1-2 weeks
4 weeks
4 weeks
2 weeks
3 months
4 Weeks
4 weeks
48 hrs
3 months
3 months
3 months
62. LONG TERM STABILITY STUDIES :
According to WHO, long term stability testing during and beyond expected shelf life
under storage conditions in the intended market.
RECOMMENDED CONDITIONS FOR LONG TERM STABILITY
ACCELERATED STABILITY STUDIES:
In , general the accelerated stability conditions must be at least 15’C above the
actual storage temperature and appropriate relative humidity . Substances and
drugs products intended to be stored in a refrigerator . the accelerated stability
studies should be carried out at 25+/-2’c and 60+/-5% relative humidity.
STORAGE CONDITIONS
TEMPERATURE (‘C) RELATIVE HUMIDITY% MINIMUM TIME
25’C+/- 2’C 60 +/- 5% 12 MONTHS
30’C +/- 2’C 30+/- 5% 6 MONTHS
STORAGE CONDITIONS
TEMPERATURE (‘C) RELATIVE HUMIDITY% MINIMUM TIME
40’C +/- 2’C 75 +/-5% 6 MONTHS
63. Testing Frequency:
For Long term testing, during first year sampling should be done
every
three months, during second year, sampling should be done every six
months and after two years, sampling should be done once a year.
Accelerated testing should be done atleast six months and it
suggests
sampling points of 0, 3, 6 months.
64. Methods Of Accelerated Stability
Testing In Dosage forms
Freeze Thaw test
Centrifugal Test
Shaking test
Elevated Temperature test
65. Accelerated Stability Testing in Emulsions
An emulsion is stored at elevated temperature. This decreases viscosity of the
continuous phase. If the emulsion withstands this stress it is assumed to be
stable at normal conditions of storage.
Centrifugation Method:
Creaming and flocculation are slow processes.
Centrifugation accelerates rate of creaming and flocculation in emulsions.
The emulsion is subjected to different centrifugal speeds and separation of
phases is observed at different time periods.
Bad emulsion separates oil instantly.
Good emulsion does not exhibit detectable separation of oil phase until certain
time period.
66. Accelerated tests for Suspensions
Cake formation is accelerated by centrifugation.
High speed centrifugation is hence not preferred, low speed centrifugation
is used to study the physical stability.
A Freeze-Thaw cycling technique is one of the stress testing . This cycling
treatment promotes particle growth and has primary importance for
changes in absolute particle size, particle size distribution and
crystal habit.
67. Accelerated Tests for moisture absorption
In this method, products are placed in an environment of high relative
humidity and controlled temperature.
Their physical and chemical stabilities are assessed.
The results will indicate whether the product is susceptible to moisture
and also whether the container needs to provide a high degree of
protection.
68. Limitations
Stability predictions based on Arrhenius equation are valid only
when the break down depends on temperature.
The energy of activation obtained in the study should be between
10 to 30 kcal/mole.
When degradation is due to
Microbial contamination
Photochemical reactions
When the product looses its physical integrity at higher temperatures.
When the order changes at elevated temperatures.
In case of disperse systems, when temperature is elevated viscosity is
decreased and this may introduce errors in the prediction of stability.
69. Describes regarding sampling times ,storage conditions&
specific test parameters for each dosage form.
The FDA & The expert working group of the ICH of technical
requirements for the registration of pharmaceuticals for
human use have published guidelines for conducting the
actual studies.
70. ICH Guidelines
• Quality Guidelines “Q” (chemical and pharmaceutical QA)
• Safety Guidelines “S” (in vitro and in vivo pre-clinical studies)
– covering Carcinogenicity Testing, Genotoxicity Testing,
Toxicokinetics and Pharmacokinetics ….. etc.
• Efficacy Guidelines “E” (clinical studies in human subject)
– Covering clinical safety, Dose Response Studies, Good
Clinical Practices, Clinical evaluation …. etc.
• Multidisciplinary Guidelines “M”
– Covering Medical Terminology, Electronic Standards for
Transmission of Regulatory Information …… etc.
– Important for Stability !
» Guideline M4: The Common Technical Document (CTD)
71. Stability Testing Q1
Stability Testing in Climatic Zone I and II (Q1A)
Photo stability Testing (Q1B)
Stability Testing for New Dosage Forms (Q1C)
Bracketing and Matrixing Designs (Q1D)
Evaluation of Stability Data (Q1E)
Stability Testing in Climatic Zones III and IV (Q1F)
Validation of Analytical Procedures (Q2)
Impurities (Q3)
Impurities in New Drug Substances (Q3A)
Impurities in New Drug Products (Q3B)
Pharmacopoeial Harmonization (Q4)
Biotechnological Products (Q5)
Specifications (Q6)
ICH – Q – Guidelines
72. DEFINITIONS
Shelf life (expiration dating period, conformance period)
Self life is the time period during which a drug product is expected to
remain within the approved specification for use, provided that it is
stored under the conditions defined on the container label.
Re-test period
The period of time during which the drug substance is expected to remain
within its specification and, therefore, can be used in the manufacture of a
given drug product, provided that the drug substance has been stored
under the defined conditions.
73. Formal stability studies
Long term and accelerated (and intermediate) studies undertaken on primary
and/or commitment batches according to a prescribed stability protocol to
establish or confirm the re-test period of an API or the shelf life of a FPP.
Stress testing – forced degradation (API)
Studies undertaken to elucidate the intrinsic stability of the API. Such testing
is part of the development strategy and is normally carried out under more
severe conditions than those used for accelerated testing.
Stress testing – forced degradation (FPP)
Studies undertaken to assess the effect of severe conditions on the FPP. Such
studies include photostability testing (see ICH Q1B) and compatibility testing
on APIs with each other in FDCs and API(s) with excipients during
formulation development.
74. Primary batch (called also exhibit batch)
A batch of an API or FPP used in a formal stability study, from which stability
data are submitted in a registration application for the purpose of establishing a
re-test period or shelf life, respectively. A primary batch of an API should be at
least a pilot scale batch. For a FPP, two of the three batches should be at least pilot
scale batch, and the third batch a production batch.
Commitment batches
Production batches of a drug substance or drug product for which the stability
studies are initiated or completed post approval through a commitment made in
the registration application.
Pilot (scale) batch
A batch of an API or FPP manufactured by a procedure fully representative of
and simulating that to be applied to a full production scale batch. (For solid oral
dosage forms, a pilot scale is generally, at a minimum, one-tenth that of a full
production scale or 100,000 tablets or capsules, whichever is the larger.)
Production (scale) batch
A batch of an API or FPP manufactured at production scale by using production
equipment in a production facility as specified in the application.
75. Specification - Release
The combination of physical, chemical, biological, and microbiological tests
and acceptance criteria that determine the suitability of a drug product at the
time of its release.
Specification - Shelf life
The combination of physical, chemical, biological, and microbiological tests
and acceptance criteria that determine the suitability of an API throughout
its re-test period, or that anFPP should meet throughout its shelf life.
Mass balance
The process of adding together the assay value and levels of degradation
products to see how closely these add up to 100% of the initial value, with
due consideration of the margin of analytical error.
76. WORLDWIDE ZONES / TEMPERATURE AND
HUMIDITY CONDITIONS
Zone Mean kinetic
temperature
Yearly average
humidity (%RH)
Zone I ( Moderate) 21 ̊C 45
Zone II (Mediterranean) 25 ̊C 60
Zone III (Hot, dry) 30 ̊C 35
Zone IV (Very hot, moist) 30̊ C 70
77. COUNTRIES AND ZONES
Regions Zone I &II Zone III&IV
EUROPE All countries
AMERICA Argentina, Bolivia, Canada,
Mexico, US
Brazil, Columbia, Cuba,
Jamaica
ASIA Afghanistan, China, Iran,
Nepal, Turkey, Japan
Bahrain , Hong Kong, India,
Oman , Pakistan, Srilanka,
UAE
AFRICA Egypt, Algeria, South Africa,
Libya
Angola, Benin, Congo,
Uganda, Sudan, Somalia,
Senegal
78. Study Storage condition
Minimum time period covered
by data at submission
Long term 25°C ± 2°C / 60% ± 5% r.h or
30°C ± 2°C / 65% ± 5% r.h.
12 months
Intermediate 30°C ± 2°C / 65% ± 5% r.h. 6 months
Accelerated 40°C ± 2°C / 75% ± 5% r.h. 6 months
STORAGE IN A REFRIGERATOR
Study Storage condition Minimum time period covered
by data at submission
Long term 5°C ± 3°C 12 months
Accelerated 25°C ± 2°C / 60% ± 5% r.h. 6 months
STORAGE CONDITIONS FOR STABILITY STUDY
API/DRUG SUBSTANCES TO BE STOTRED AT AMBIENT TEMPERATURES
Study Storage condition Minimum time period
covered by data at
submission
Long term -20°C ± 5°C 12 months
STORAGE IN FREEZER
79. DRUG PRODUCTS - PACKAGED IN
SEMI-PERMEABLE CONTAINERS
Study Storage condition Minimum time period
covered by data at
submission
Long term 25°C ± 2°C / 40% ± 5% r.h. or
30°C ± 2°C / 35% ± 5% r.h.
12 months
Intermediate 30°C ± 2°C / 65% ± 5% r.h. 6 months
Accelerated 30°C ± 2°C / 65% ± 5% r.h. 6 months
80.
81. The Stability Chambers are designed for an operating range of 4°C to
70°C Temperature only, 5°C to 60°C Temperature with Humidity.
These units employ a programmable controller to control the
temperature, defrost and humidity settings. The cabinets use an
evaporator coil, located on top of the cabinet as the heat-removing
source. Through the refrigeration process, heat is captured in the
evaporator, transferred to the condensing unit on top of the cabinet,
and expelled to the surrounding outside air. It is extremely important
to allow a four-inch clearance on the top, rear, and sides of the unit
for the refrigeration process to function properly.
84. Packaging And Stability
1.Glass
Glass is resistant to chemical and
physical change and is the most commonly used material.
Limitations Overcome
1. Its alkaline surface use of Borosilicate glass
2. Ions may precipitate
insoluble crystals from the
glass
the use of buffers
3- Permits the transmission
of light which may accelerate
decomposition.
Amber coloured glass
85. Packing and Stability
2.PLASTICS
The problems with plastic are:
Migration of the drug through the plastic into the
environment.
Transfer of environmental moisture, oxygen, and other
elements into the pharmaceutical product.
Leaching of container ingredients into the drug.
Adsorption of the active drug or
excipients by the plastic.
86. Packing and Stability
3.Metals
Various alloys and aluminum tubes may be utilized as
containers for emulsions, ointments, creams and pastes.
Limitation: They may cause corrosion and precipitation in
the drug product.
Overcome: Coating the tubes with polymers may reduce
these tendencies.
87. Packing and Stability
Rubber
Rubber also has the problems of extraction of drug
ingredients and leaching of container ingredients.
The pretreatment of rubber vial stoppers and closures with
water and steam reduces potential leaching.
88. Physical stability
Formulation Likely physical
instability
problems
Effects
Capsules Change in:
a) Appearance
b) Dissolution
c) Strength
Change in drug
release
89. Types of Stability Studies
1.Long-Term (Real-Time) Stability Testing
Stability evaluation of the physical, chemical, biological
and microbiological characteristics of a drug product
duration of the shelf life
90. Packaging materials permeable to water vapor result in a
falsification of the results for semisolid and liquid dosage forms if
varying degrees of weight loss occur that leads to differences in the
active ingredient concentration or ion strength.
The use of inert standard packaging materials that are impermeable
to water vapor is important precondition for stress tests that are
evaluated in terms of reaction kinetics, and on the results on which
stability predictions are to be tested.
91. Solid dosage forms: 50-mL glass container with twist-off closure
polypropylene tube
Semisolid dosage forms: Standard tube, small volumetric flask,
Aluminum tube, inert internal lacquering
Liquid dosage forms: 25mL volumetric flask with ground-glass
stopper
However, furture investigations for the selection of the final
packaging are necessary.
92. On the basis of the results of the stress tests for solid dosage forms,
the sensitivity to moisture can be determined and suitable
packaging materials can be selected.
As a rule, no interactions are to be expected.
If the final packaging material has been selected and samples
packed in the final packaging material are available, the
investigation of photostability should be performed.
Photostability :The samples with and without container are
irradiated with a Xenon lamp for 24 hours.
93. Packaging: Aluminum tube internally lacquered, plastic tubes.
Problems: Corrosion , permeation, sorption.
Tests packaging material – dosage form:
To test for corrosion ,the filled metal tubes are stored horizontally
upright and inverted at 400C, for 3 months and are then
investigated.
To test for permeation and sorption the filled plastic tubes are
stored for 3 months at 500C, 400C, 300C/70%.
If the final packaging material has been selected, the investigations
on the photostability are performed.
94. Packaging ampoule, injection vial with rubber stopper, glass bottle
or plastic bottle with screw closure.
Problems: leakage.
To test for permeation, and leakage, the finale formulation solution
is filled in the container, and for desorption placebo solution is
used.
The samples are stored vertically and inverted under 500C, 400C,
300C/70% for up to 12 weeks.
Tested intervals: 0, 1, 2, 3 months.
If the final packaging material has been selected the investigations
on the photostability are performed.
95. TABLET
Stable tablets retain their original size ,shape , weight ,roughness ,colour variation ,
cracking under normal handling and storage conditions throughout their shelf life.
• FRIABILITY TEST : studies revel the physical instability if any in tablet.
Maximum weight loss should not be more than 1%.
• HARDNESS TEST : shows resistance to crushing.
• COLOR STABILITY : by colorimeter , reflectometer with heat , sunlight and intense
artificial light.
Uniformity of weight , odor , texture , drug and moisture content , humidity effects
are also Studied during a tablet test.
96. GELATINE CAPSULE
Gelatin capsules are found to be stable in dry
conditions but they rapidly reach equilibrium with
the atmospheric conditions under they are stored.
This shows gelatin capsules are largely effected by
temperature and humidity and susceptibility to
microbial degradation .
soft gelatin capsule have Relative Humidity 20 to
30% at 21 to 24’C.
hard gelatin capsule contain 13 to 16% moisture.
Humidity - capsule shell softens and becomes
sticky.
Dried- capsule shell becomes brittle and crack.
Hard gelatin capsule are tested for Brittleness ,
dissolution , water content and level of microbial
contamination.
97. EMULSIONS
Tested for phase separation , PH , viscosity , level of microbial
contamination , and distribution of dispersed globules.
ORAL SOLUTIONS AND SUSPENSIONS
Formation of precipitate , clarity for solutions , PH , viscosity ,
microbial contamination.
Additionally for suspensions , redispersibility , rheological
properties ,mean size and distribution of particles should be
considered .
NASAL SPRAYS : solution and suspensions
Clarity (for solution) , level of microbial contamination , PH ,
particulate matter , unit spray medication , content uniformity
, droplet and/or particle size distribution , weight loss , pump
delivery.
Microscopic evaluation ,(for suspension) , foreign particulate
matter and extractable/ leachable from components of the
container , closure and pump.
TOPICAL , OPTHALMIC AND OTIC PREPRATION
Included in this broad category are ointments ,creams , lotions
,paste , gel , solutions ,eye drops and cutaneous sprays.
98. TOPICAL
preparations should be evaluated for clarity , homogeneity , PH ,
resuspendibility for lotions , consistency , viscosity , particle size
distribution ,level of microbial contamination / sterility and weight
loss
FOR OPTHALMIC OR OTIC PREPRATION
Should include the following additional attributes : sterility
,particulate matter ,and extractable.
SUPPOSITORIES
Softening range , dissolution (at 37’C)
PARENTERALS
Color , clarity (for solutions) , particulate matter , PH, sterility ,
pyogen / endotoxins .
Stability studies for powders for injection solution ,include color
monitoring , reconstitution time and water content ,to be performed
at regular intervals .