The document outlines stability testing for pharmaceutical products, detailing definitions, objectives, and methods involved in ensuring drug quality and efficacy over time. It emphasizes the significance of stability studies in establishing shelf life, identifying storage conditions, and preventing degradation that could impact therapeutic effectiveness. Additionally, the document references various international guidelines and regulatory requirements pertinent to stability testing in pharmaceuticals.

1. ANDHRA PRADESH STATE SKILL DEVELOPMENT CORPORATION
(Department skill development & training, Govt of Andhra Pradesh)
CHEBROLU HANUMAIAH INSTITUTE OF PHARMACEUTICAL
SCIENCES
Chandramoulipuram, Chowdavaram, Guntur – 522019, Andhra Pradesh.
(Sponsored by Nagarjuna Education Society)
Approved by AICTE & PCI, Affiliated to Acharya Nagarjuna University.
Recognized by Govt. of Andhra Pradesh, An ISO 9001:2015 Certified Institute.
Accredited by NAAC
Presented by
Dr. J. Ramesh babu, M.Pharm., Ph.D.
Professor & HOD
HANDS ON TRAINING ON MACHINERY USED FOR
PHARMACEUTICAL PRODUCT DEVELOPMENTS

3. ABBREVIATIONS
API Active Pharmaceutical Ingredient
DRA Drug Regulatory Authority
EoI Expression of Interest
FDC Fixed-Dose Combination
FPP Finished Pharmaceutical Product
GMP Good Manufacturing Practices
ICH International Conference on Harmonization
MA Marketing Authorization
PQIF Pharmaceutical Quality
Information Form
Yellow → emphasis Green → WHO Blue → ICH region

4. ESSENTIAL ICH
DEFINITIONS
STABILITY STUDIES

5. SELECTED DEFINITIONS
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.
Shelf life (expiration dating period, conformance period)
The time period during which an API or a FPP is expected to
remain within the approved shelf-life specification, provided
that it is stored under the conditions defined on the container
label.

6. SELECTED DEFINITIONS
 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.

7. SELECTED DEFINITIONS
 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.
7/60

8. SELECTED DEFINITIONS
 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.

9. SELECTED DEFINITIONS
 Supporting data
Data, other than those from formal stability studies, that support the
analytical procedures, the proposed re-test period or shelf life, and the label
storage statements. Such data include (1) stability data on early synthetic route
batches of API, small-scale batches of materials, investigational formulations
not proposed for marketing, related formulations, and product presented in
containers and closures other than those proposed for marketing; (2)
information regarding test results on containers; and (3) other scientific
rationales.

10. SELECTED DEFINITIONS
 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.

11. CONTENTS :
 Definition
 Objectives Of Stability Study
 Application Of Stability Studies In Pharmaceuticals
 Factors Affecting Drug Stability
 Design Of Stability Program
 The Role Of Stability Testing
 Requirements Of Stability Testing Under Indian Drug Laws
 ICH Stability Guidelines
 Different Steps Involved In Stability Study
 Conclusion
 References

12. DEFINITION:
 Drug Stability refers to the capacity of a drug substance or product to remain within
established specifications of identity, strength, quality, and purity in a specified
period of time.
 Stability is officially defined as the time lapse during which the drug product
retains the same properties and characteristics that it possessed at the time of
manufacture.
 The stability of a product is expressed as the expiry period or technically as shelf
life.
OBJECTIVES
 To gather information during preformulation stage to produce a stable product.
 To determine maximum expiration date.
 To get an idea of storage condition.
 To determine the packaging components.
 The retest period of pharmaceuticals.
 Transport conditions.

13. APPLICATION OF STABILITY STUDIES
IN PHARMACEUTICALS :
 Chemical degradation of active drug may reduce the quality of therapeutic indices like 5-
flurouracil, carbamazepine etc have very small therapeutic range, slight degradation of
drug may produce sub therapeutic concentration.
 After degradation a drug may produce more toxic product(s) which may be more toxic
than the parent product.
 Instability of drug product reduce bioavailability. This may be caused by physical or
chemical instability.
 Instability of a product may change the physical appearance of the product.
 FACTORS AFFECTING DRUG STABILITY
 Storage time
 Storage condition
 Type of dosage form
 Container and closure system

14. WHY SO MUCH EMPHASIS ON RIGHT
PRACTICES IN STABILITY TESTING?
 The ideal production environment
- Regulations and Controls
- GMP
- GLP
 The non-ideal shipment and storage environment Transport
Wholesalers
Retailers
Patients
Mishandling

15. THE STORAGE FACILITIES CURRENTLY
AVAILABLE IN THE RETAIL DRUG OUTLETS AND
PHARMACIES INCLUDE:-
 A refrigerator, mostly of 165 litres size.
 Freezer compartment of the same refrigerator.
 Open shelves [storage at ambient temperature and light of the
outlet).
 Covered cupboards/drawers that do provide protection from light
at ambient temperature of the outlet.
 Air-conditioning, but only of 10% outlets, providing an
environment of <30°C.

16. THE POSSIBLE CHANGES (INVISIBLE AND VISIBLE)
:
 Loss of active ingredient
 Alteration in bioavailability
 Loss of content uniformity
 Decline of microbiological status
 Loss of pharmaceutical elegance and patient acceptability
 Formation of toxic degradation products
 Loss of package integrity
 Reduction of label quality
 Modification of any factor of functional relevance (dissolution,
release, etc.)

17. THE ROLE OF STABILITY TESTING :
 Provides evidence on how the drug substance or product quality varies with
time under environmental conditions during distribution
 Helps to recommend storage conditions, including establishment of shelf life,
expiry date or retest period
 Key to assurance of quality of pharmaceuticals .
 REQUIREMENTS OF STABILITY TESTING UNDER
INDIAN DRUG LAWS.
 Quality control department shall
 control the quality and stability of finished product
 The quality control department shall have the following principle duties:
(Viii) - “to establish shelf life and storage requirements on the basis of
stability tests related to storage conditions

18. WHO TRS 823 OF 1992 (16.17 TO 16.20) :
 Quality Control department should evaluate the quality and stability of finished
pharmaceutical product and, when necessary, of starting materials and
intermediate products.
 Quality Control department should establish expiry dates and shelf life
specifications on the basis of stability tests related to storage conditions.
 Stability study should be determined prior to marketing and following any
significant changes in processes, equipment and packaging material etc.
 A written program for on going stability determinations should be developed
and implemented.

19. ORIGINAL ICH STABILITY GUIDELINES
Q1A Stability testing of
New drugs and
products
October 1993
Q1B Stability testing : Photo
Stability testing
November 1996
Q1C Stability testing for new
Dosage form
November 1996
Q5C Stability testing of
biotechnological /
biological
November 1995
Q1- Stability Guidance document
Guideline number Year of publication
Q1A 1993
Q1A(R) Nov. 2000
Q1A(R2) Feb. 2003

20. OTHER ICH STABILITY GUIDELINES :
Q1D Bracketing and matrixing
Designs for stability testing
February 2003
Q1E Evaluation of stability data February 2003
Q1F Stability data package for
Registration in Zone III and IV
February 2003(Withdrawn
June 2006)
Applicability of these Guidelines :
ICH New drug products
WHO Existing drugs and products
US FDA Comprehensive, covers IND,
NDA, ANDA
CPMP Existing drugs
VICH New drugs and products

21. APPLICABILITY OF THESE GUIDELINES :
ICH New drug products
WHO Existing drugs and products
US FDA Comprehensive, covers IND, NDA,
ANDA
CPMP Existing drugs
VICH New drugs and products

22. ICH GUIDELINES ON STRESS TESTING
Standard Title and reference
ICH Q1A(R2) Stability Testing of New Drug Substances and Products
(the parent guideline)
ICH Q1B Photostability Testing of New Drug Substances and
Products
ICH Q2B Validation of Analytical Procedures: Methodology
ICH Q3A(R) Impurities in New Drug Substances
ICH Q3B(R) Impurities in New Drug Products

23. DESIGN OF STABILITY PROGRAM
 The design of the stability program for the finished product is based on the
knowledge of the drug substance and experience gained from clinical
formulation study & stability study.
 It should state the storage condition and the rational change in the dosage form.
 Different steps involved :
 Test procedure & test criteria
 Specifications
 Selection of batches
 Storage test condition
 Testing frequency
 Packaging material
 Evaluation
 Statements & labeling


24. TEST PROCEDURE & CRITERIA :
 Test procedure & criteria It must cover those features which are susceptible to
change during storage & likely effect quality, safety & efficacy.
 Analytical procedure should be fully validated and that should be stability indicating
 The testing not only include chemical & biological stability but also loss of
preservative, physical, organoleptic properties & also microbiological attributes.
 Preservative efficacy testing should be done on stored sample.
 Specifications :
Specification is a list of:-
 Tests & test attributes
 References to analytical procedure
 Acceptance criteria


25. TESTING FREQUENCY :
 Long term studies
 Accelerated studies
generally minimum three points
e.g.:-0, 3, 6 months
 Intermediate studies
minimum four time points e.g.:-0, 6, 9, 12 months
. Storage conditions :
. . Storage conditions for
- different zones
- type of study – long term/accelerated
- different product types

26. THE ZONE CONCEPT :
ZONE I
MODERATE
ZONE II
MEDITERRANEAN
ZONE III
HOT / DRY
ZONE IV
VERY HOT /
MOIST
Kinetic average
Temperature
21 ̊c
Kinetic average
Temperature 25 ̊c
Kinetic average
Temperature 30 ̊c
Kinetic average
Temperature 30 ̊c
Yearly average
Humidity 45%
R.H
Yearly average
Humidity 60% R.H
Yearly average
Humidity 35% R.H
Yearly average
Humidity 70% R.H

27. Region Zone I and II ZONE III and IV
Europe All countries --------------------
America Argentina, Bolivia, Chile, Canada,
Mexico, Peru, Uruguay, USA
Barbados, Belize, Brazil, Coastarica,
Dominican republic, Ecuador, El
Salvadar , Guyana, Hiita, Honduras,
Jamaica , Columbia, Cuba, Panama,
uraguay, Puerto Rico, Venezuela. All
these countries are assigned to CZ IV
Asia Afghanistan, Armenia, China, Georgia,
Iran, Israel, Japan, Kazakhsthan,
Korea, Lebanon, Nepal, Syria, Turkey,
Turkmenesia, Uzbekistan
Behrain, Bangladesh, HongKong,
India, Indonesia, Iraq(III), Jordan(III),
Qatar, Kuwait, Laos, Malaysia,
Maldives Island, Oman, Pakistan,
Saudi Arabia, Singapore, Sri Lanka,
Taiwan, Thailand, UAE, Vietnam,
Yemen
Africa Egypt, Algeria, Tunisia, Libya,
Morocco, Namibia, south Africa,
Zambia, Zimbabwe .
Angola, Ethiopia, Benin, Bostwana,
Burundi, Djibouti, Ivory coast, Gaban,
Gambia, Ghana, Guinea, Cameroon,
Kenya, Congo, Liberia, Madagascar,
Niger, Nigeria, Senegal, Sudan,
Somalia, Togo, Central African
Republic
Australian/ Oceanic Australia and New zealand Figi, Society Islands, marshal islands,
New caledonia, New guinea, Tonga,
Samoa.

28. STORAGE CONDITIONS FOR GENERAL PRODUCTS :
*It is applicant to decide whether the long term studies are performed at 25 ± 2 ̊c / 60%
RH ± 5 %RH or 30 ̊c ± 2 ̊c / 65% RH ± 5 %RH
** 30 ̊c ± 2 ̊c / 65% RH ± 5 %RH is the long term condition, there is no intermediate
condition.
Study Storage condition Minimum time period
covered by data at
submission
Long term* 25 ̊c ± 2 ̊c / 60% RH ± 5 %RH
Or
30 ̊c ± 2 ̊c / 65% RH ± 5 %RH
12 months
Intermediate** 30 ̊c ± 2 ̊c / 65% RH ± 5 %RH 6 months
Accelerated 45 ̊c ± 2 ̊c / 75% RH ± 5 %RH 6 months

29. STORAGE CONDITIONS FOR LIQUID PRODUCTS PACKED IN
SEMI- PERMEABLE CONTAINERS
*
*It is applicant to decide whether the long term studies are performed at 25 ± 2 ̊c / 60%
RH ± 5 %RH or 30 ̊c ± 2 ̊c / 65% RH ± 5 %RH
** 30 ̊c ± 2 ̊c / 65% RH ± 5 %RH is the long term condition, there is no intermediate
condition.
Study Storage condition Minimum time
period covered
by data at
submission
Long term* 25 ̊c ± 2 ̊c / 60% RH ± 5 %RH
Or
30 ̊c ± 2 ̊c / 65% RH ± 5 %RH
12 months
Intermediate** 30 ̊c ± 2 ̊c / 65% RH ± 5 %RH 6 months
Accelerated 45 ̊c ± 2 ̊c / not more than
(NMT)25% RH
6 months

30. STORAGE CONDITION IN ACCORDANCE WITH
ICHQ1A (R2) AND Q1F
 When significant changes occur due to accelerated testing, additional testing at an intermediate condition 30 ̊c
± 2 ̊c / 65% RH ± 5 %RH should be significant
 According to ICH significant change in drug product are:-
 A 5% change in assay value from initial
 Any degradation products exceeds its set limits
 Failure to meet acceptance criteria
 The PH value and dissolution no longer satisfies the requirement
Study Zone I and II Zone III and IV
Long term 25 ̊c ± 2 ̊c / 60% RH ± 5
%RH
30 ̊c ± 2 ̊c / 65% RH ±
5 %RH
Intermediate 30 ̊c ± 2 ̊c / 65% RH ± 5
%RH
--------------------
Accelerated 40 ̊c ± 2 ̊c / 75% RH ± 5
%RH
40 ̊c ± 2 ̊c / 75% RH ± 5
%RH

31. STANDARD STORAGE CONDITION FOR
TEMPERATURE SENSITIVE PRODUCTS
Note: Freezer temperature storage of -15 ̊c +
5 ̊c was specified in FDA
Storage condition Temperature and relative
humidity
Refrigerator storage 5 ̊c to 8 ̊c/ monitored
Freezer storage -20 to -13 ̊c

32. TERMINOLOGY –
ADAPTED FROM ICH Q1A 2000 (6)
Reduced study designs:
- Bracketing
- A design in which only the extremes are tested at all
time points, eg strength, pack size, container fill
- Matrixing
- Designs in which a selected subset of samples is
tested, eg different strengths, container/closure
systems, batches

33. EXAMPLE OF A BRACKETING DESIGN
Strength 50mg 75mg 100mg
Batch 1 2 3 1 2 3 1 2 3
15ml T T T T T T
100ml
Container
size
500ml T T T T T T
T = Sample is tested

34. EXAMPLE OF A MATRIXING DESIGN
“ONE HALF REDUCTION”
Time point (months) 0 3 6 9 12 18 24 36
Batch
1
T T T T T T
Batch
2
T T T T T T
S1
Batch
3
T T T T T
Batch
1
T T T T T
Batch
2
T T T T T T
Strength
S2
Batch
3
T T T T T
T = Sample is tested

35. WHEN MIGHT BRACKETING & MATRIXING BE APPROPRIATE?
(NB THE FOLLOWING IS NOT FROM ICH ! YOU MUST ARGUE THE
CASE!)
- Container size?
- Batch size?
- Formulation of coating?
- With varying amounts of an excipient (eg starch, Mg stearate)?
The risk associated with bracketing & matrixing
-If the results are not what you expected, you may have
insufficient to propose an intermediate shelf life
-Would be risky to use bracketing & matrixing if you did
not have a good idea as to what the product’s stability will
be
-Consequently: Bracketing & matrixing designs are used
mainly for confirmatory studies

36. CLASSES OF DEGRADATION
- Chemical
- Physical
- Microbiological
Physical degradation
(≡ physicochemical degradation)
-Physical properties can change too!
-Important attributes vary with dosage form
-Bottom line is relevance to quality, safety & efficacy
-Examples for liquid formulations:
-Appearance, colour, odour, pH, clarity (solutions) and freedom from visible
particulate contamination, size range of particulate contamination (large
volume parenterals), particle size distribution (suspensions), micelle size
distribution (micellar solutions), resuspendability (suspensions), viscosity,
moisture content (powders for reconstitution), phase separation (emulsions)

37. OTHER FORMS OF PHYSICAL DETERIORATION MAY
INCLUDE:
- Leaching
- Absorption (into container walls)
- Adsorption (on to container walls)
- Volatilisation (eg sertraline base, glyceryl trinitrate)
- Altered particle size distribution
- Loss of higher order molecular structure (normally only for biological medicines)
- Denaturation
- Aggregation.
Minimising physical deterioration
- Some examples:
- When prone to adsorption on to, or absorption into, packaging materials, use
resistant packaging materials, such as good quality glass
- When prone to volatilisation:
- Use a non-volatile salt (if possible)
- Use packaging materials that are resistant to vapour transfer
- When prone to altered particle size in suspensions:
- Formulate a continuous phase in which the active is less soluble

38. MICROBIOLOGICAL DETERIORATION
 Proliferation of microbes in non-sterile products
 Consequences may include:
 Infection of the patient
 Formation of endotoxins (≡ pyrogens)
 Foul odour
- Formation of gas
- Change in colour
- Cloudiness
- Hydrolysis.
Minimising microbiological deterioration of non-sterile
products
-Control the microbial load of API & excipients
-Validate & monitor manufacturing conditions
-Include antimicrobial preservatives in formulations
-NB Normally only bacteriostatic & not bactericidal

39. APPROPRIATE TESTS FOR STABILITY
STUDIES - 1
- Normally test same attributes as for routine QC
- May use other methodology for stability testing (avoid for
dissolution rate) but must be validated
- Avoid changing methodology mid-study (unless correcting
a clear deficiency)

40. APPROPRIATE TESTS FOR
STABILITY STUDIES - 2
- Quantitate degradation products if possible, even if the
assay is specific for the API
- But can be difficult to quantitate impurities if there are
no reference standards & relative response factors are
unknown → semiquantitative estimates
- Regulatory authorities usually expect an approximate
mass balance
- Appropriate physical tests vary with dosage form.
- Remember to conduct preservative efficacy tests too, in
addition to assay of any antimicrobial preservative

41. FOR ALL STABILITY STUDIES
 Validate the analytical methodology!
 See relevant guidelines, especially:
 Validation of analytical procedures: Terminology
ICH Q2A 1994
 Validation of analytical procedures: Methodology
ICH Q2B 1996
 Use stability-indicating assays

42. DISSOLUTION RATE
- Avoid using a method different to that in routine QC
- Most regulatory authorities, including PQP, prefer dissolution
profiles rather than single time points during stability testing.
Better ability to detect trends.
- Avoid using a method different to that in routine QC
- Most regulatory authorities, including PQP, prefer dissolution
profiles rather than single time points during stability testing.
Better ability to detect trends.

43. EVALUATION / INTERPRETATION
OF THE RESULTS
So what’s the shelf life?
 The validity of an assigned shelf
life depends upon:
- The results of stability studies,
&
- Whether the batches used in the
stability studies accurately
model those to be marketed, &
- Whether analytical methodology
was adequately validated

44. ASSIGNING A SHELF LIFE
 Assigning a shelf life is easier if results are available:
- For the full duration of the proposed shelf life
- At the maximum recommended storage conditions
- For all formulations & manufacturing methods
- In exactly the packaging to be registered
- At all sites of manufacture of finished product & API
 If these conditions are not met, that’s when shelf life
assignment becomes difficult.
 There will be arguments between manufacturers &
registration/prequalification authorities
 There will be delays in approving the product

45. WHAT ARE THE LIMITATIONS OF
THIS STATISTICALALGORITHM?
- It applies only to quantitative attributes
Does not apply for example to colour tests, or to semiquantitative
comparisons such as TLC limit tests
- It may be unreliable for physical attributes
Such as dissolution tests & discoloration
- Use your judgement! Look at the slope of
the curve. Does the change accelerate with
time?

46. FACTORS TO BE TAKEN INTO ACCOUNT WHEN
ASSIGNING A SHELF LIFE BASED ON STATISTICAL
ANALYSIS - 1
- Release limits
- Expiry limits
- Results of stability studies
- Is there any desired safety margin?
This is largely a matter for the manufacturer/supplier.
Based on statistical analysis – 2
 A batch may be released with a result anywhere in range
of release limits
 Consequently a prudent manufacturer will take into
account the lower limit of release when estimating shelf
life

47. A COMPREHENSIVE STABILITY EVALUATION :
 Physical
 Chemical
 Microbiological
 Toxic
 Therapeutic

48. EVALUATION :
 A systematic approach should be adopted in the presentation and evaluation of
the stability information which covers the physical, chemical & biological
parameter.
 A minimum of 3 batches of drug product should be tested.
 The analyst must find the batch to batch variability & if it is small than only it
is accepted & it can be done by different statistical tests(P value for level of
significance for rejection).
 When the data shows so little degradation & so little variability that is
apparent from looking the data that the requested shelf life will be
granted & it is normally unnecessary to go through the formal statistical
analysis.
 The stability of the drug product after reconstitution or dilution
according to labeling should be addressed to provide appropriate and
supportive information.

49. Description of the conditions of storage (standardized conditions for long
term testing as described in this guideline, and consistent with the
product labelling, should be used);
Other applicable parameters specific to the pharmaceutical product.
TESTING PARAMETERS
1. Tablets
Dissolution (or disintegration, if justified), water content and
hardness/friability.
2. Capsules
 Hard gelatin capsules: brittleness, dissolution (or disintegration, if justified),
water content, and level of microbial contamination.
 Soft gelatin capsules: Dissolution (or disintegration, if justified), level of
microbial contamination, pH, leakage, and pellicle formation.

50. 3. Emulsions
Phase separation, pH, viscosity, level of microbial contamination, and
mean size and distribution of dispersed globules.
4. Oral Solutions and Suspensions
Formation of precipitate, clarity for solutions, pH, viscosity,
extractables, level of microbial contamination. Also, polymorphic
conversion may be examined, if applicable.
Additionally for suspensions, redispersibility, rheological properties
and mean size and distribution of particles should be considered.
5. Powders for oral solution or suspension
Water content, and reconstitution time. Reconstituted products
(solutions and suspensions) should be evaluated as described in “Oral
Solutions and Suspensions” above, after preparation according to the
recommended labeling, through the maximum intended use period.

51. 6. Metered-dose Inhalers and Nasal Aerosols
Dose content uniformity, labelled number of medication actuations per container
meeting dose content uniformity, aerodynamic particle size distribution, microscopic
evaluation, water content, leak rate, level of microbial contamination, valve delivery (shot
weight) and extractables/leachables from plastic and elastomeric components. Samples should
be stored in upright and inverted/on-the-side orientations.
7. Nasal Sprays: Solutions and Suspensions
Clarity (for solution), level of microbial contamination, pH, particulate matter, unit
spray medication content uniformity, number of actuations meeting unit spray content
uniformity per container, droplet and/or particle size distribution, weight loss, pump delivery,
microscopic evaluation (for suspensions), foreign particulate matter and
extractable/bleachable from plastic and elastomeric components of the container, closure and
pump.
8. Topical, Ophthalmic and Otic Preparations
Included in this broad category are ointments, creams, lotions, paste, gel, solutions, eye
drops, and cutaneous sprays.
Topical preparations should be evaluated for clarity, homogeneity, pH, resuspendability
(for lotions), consistency, viscosity, particle size distribution (for suspensions, when feasible),
level of microbial contamination/sterility and weight loss (when appropriate).

52. Evaluation of ophthalmic or otic products (e.g., creams, ointments, solutions, and
suspensions) should include the following additional attributes: sterility, particulate
matter, and extractable. Evaluation of cutaneous sprays should include: Pressure,
weight loss, net weight dispensed, delivery rate, level of microbial contamination,
spray pattern, water content, and particle size distribution (for suspensions).
9. Suppositories
Softening range, dissolution (at 37°C).
10. Small Volume Parenterals (SVPs)
Colour, clarity (for solutions), particulate matter, pH, sterility, endotoxins.
Stability studies for powders for injection solution should include monitoring for
colour, reconstitution time and water content. Specific parameters to be examined at
appropriate intervals throughout the maximum intended use period of the
reconstituted drug product, stored under condition(s) recommended in labelling,
should include clarity, colour, pH, sterility, pyrogen/endotoxin and particulate
matter.
The stability studies for Suspension for Injection should include in addition
particle size distribution, redispersibility and rheological properties.

53. The stability studies for Emulsion for Injection
should include in addition phase separation, viscosity, and
mean size and distribution of dispersed phase globules.
11. Large Volume Parenterals (LVPs)
Colour, clarity, particulate matter, pH, sterility,
pyrogen/endotoxin, and volume.
12. Transdermal Patches
In-vitro release rates, leakage, level of microbial
contamination/sterility, peel and adhesive forces.

54. CONCLUSION
 Stability is an essential quality attribute for drug products.
 Stability testing is not done for creating data for regulators,
but as an assurance to manufacturer itself on the quality of its
products.
 Has to be done on all the products in the market.
 Structured, systematic and documented stability testing
based on right principles can save manufacturers from lot of
undue hassles, faced when product is proved to be of inferior
quality.

55. REFERENCES
:
 Dr.Ali Javed Khan, R.K.Ahuja Alka, Text book of dosage form
design,2004.
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