Stability is important for drug products to remain within specified limits of identity, strength, quality and purity during storage and use. The stability of solid dosage forms is most commonly studied to understand drug degradation. Many factors can influence degradation, including temperature, humidity, light, and the drug's excipients. Preformulation studies help identify stable storage conditions and compatible excipients to minimize decomposition for new drug substances and solid formulations.

2. • Stability means the extend to which the product or
substance remains within specified limit of identity ,
strength, quality & purity throughout its period of storage
and use.
• Need: It provides an evidence on how the quality of a
drug product degrades with time under the influence of
various factor- Temperature Humidity Light Shelf life of
drug product Storage condition solvent.

3. • The stability of drugs in solid dosage form is most
important and common for the study of degradation of
drug substance or drug product. Solid dosage form
decomposes by either first- or zero-order profile.

4. • Drugs in liquid or solid dosage forms susceptible to
chemical decomposition which leads to
• physical changes (discoloration)
• Chemical changes (loss of potency)
• Therapeutic instability
• Toxicological instability
• Microbial degradation

5. • Water-soluble drugs present in solid dosage form will
dissolve in any moisture which has absorbed in solid
surface. The drug will now be in an aqueous enviroment
and its decomposition would be now influence by many
of factors which also affect liquid dosage form.
• Moisture is considered to be most important factor that
must be control in order to minimized decomposition.

6. • Excipient such as starch and povidone having
particularly high water content. This high moisture level
has an effect on stability depend upon how strongly it is
bound and whether the moisture can come in contact
with drug.
• Meganisum trisilicate affect the drug apirin because it has
high water contant.

7. • The drug or one of the excipient may e.g
• Melt or change its polymorphic form whether change in
temprature.
• It may contain loosely bound water which is lost at high
temprature.
• The relative humidity is change with temprature so we
must take care whether remains its constant.

8. • The stability problem which arise with drugs which are
susceptible with photodecomposition or oxidation. Water
contain dissolve oxygen so the moisture present on
surface of solid drugs may cause oxidation. Such drugs
must be store under dry conditions.

9. • Preformulation study give first quantitative assesment of
chemical stability of new drug
• chemical stability
Solution
state
Solid
state

10. AIM
• Identifications of stable storage conditions for drug in the
solid state and identification of compatible excipients for
a formulations
formulations.
• Affected by change in purity and crystal property.
• Solid state is slower and difficult to interpret than solution
state.
• TLC, UV-Vis, fluorescence
• Polymorphic changes – DSC, IR or appearance changes

11. • Storage conditions Storage conditions
• Refrigerator- 5°C
• Room temp.- 22-25°C
• Ambient humidity 70%
• RH 90%
• 25°C/60% RH, 40°C/75% RH
• Light- Clear, Amber, yellow-green glass, control sample

12. • The elevated temperatures commonly used are and 60
degree centigrade with ambient humidity.
• The samples stored at highest temperature are observed
weekly for physical and chemical change and compared
to an appropriate control .
• If a substantial change is seen, samples stored at lower
temperature are examined.
• If no changes is seen after 30 days at 60°C , the stability
prognosis is excellent.

13. • Solid drug samples can be exposed to different relative
humidity conditions by keeping them in laboratory
desiccators containing saturated solutions of various
salts.
• The closed desiccator in turn are kept in oven to provide
constant temperature.

14. • Many drugs faded on exposure light due to Increased
Impurity level . Samples should be exposed to light
providing an overall illumination of not less than 1.2
million lux hours.
• If protected samples protected samples (e.g., wrapped in
aluminum foil) are used as dark controls to evaluate the
contribution.

15. • Drug’s sensitivity to oxidation can be examined by
exposing it to atmosphere of high oxygen tension.
exposing it to atmosphere of high oxygen tension.
• Usually a 40% oxygen atmosphere allows for rapid
evaluation.

16. • Colour:-Stability problems, improve appearance by
including dye in body or coating
• Taste:-palatability, flavours, and excepient may be
added.
• Odour:-degradation products, eg. Aspirin stable form of
drug to be used, flavours and excepients may be used.

17. Colour
Off-white
Cream / yellow
Shiny
odour
pungent
sulfurous
Aromatic
Sweet , odourless
taste
acidic
bitter
Intense sweet
tasteless

18. • Purity studies are essential for further studies to be
carried out safely. Impurities may make a compound toxic
or render it unstable. TLC,HPLC,GC and Paper
chromatography used. HPLC-Impurity Index(II),
Homogeneity index(HI). DTA, gravimetric analysis and
melting point by hot stage microscopy are other
techniques.
• Impurity index(II):defined as the ratio of all responses
(peak areas) due to components other than the main

19. • Differential thermal analysis(DTA)
• Thermo gravimetric analysis(TGA)
• Differential scanning calorimetry (DSC)
• Powder X-Ray Diffraction(PXRD)

20. • Various chemical and physical properties of drug
substances are affected by their particle size distribution
and shapes.
• The effect is not only on physical properties as well as
biopharmaceutical behavior.
• It also influence the flow and the mixing efficacy of
powders and granules.
• Fine materials are relatively more open to attack from
atmospheric oxygen, humidity, than that of coarse
material.

21. • Microscopy. Eg. Light microscope, electron microscope.
• Sieving method
• Instruments based on light blockage(HIAC) and blockage
of electrical conductivity path(coulter counter are
available).

22. technique particle size
Microscopic 1 - 100
Sieve > 50
Sedimentation > 1
Elutriation 1 - 50
Light scattering 0.5 - 50

23. • It is determined based on
• Brunaver Emitter Teller (BET)theory of adsorption.
• Most substances adsorb mono molecular layer of gas
(Nitrogen) and temperature.
• Air adsorption and permeability methods.

24. • All substances are transparent examined under
microscope – are either isotropic or anisotropic.
• Isotropic substances do not transmit the light – appears
black – and have single refractive index. E.g. Sodium
Chloride
• Anisotropic substances – more than one refractive index
– appear bright and brilliant color – uniaxial and biaxial
• Color depends upon – thickness of crystal and diff. in
refractive indexs.

25. • Differential Scanning Colorimetry (DSC) and Differential
Thermal Analysis (DTH) measures the heat loss or heat
gain - resulting from physical or chemical changes.
• Two types of processes
• 1) Endothermic : like fusion, boiling, sublimation,
vaporization.
• 2)Exothermic : like crystallization,degradation
Quantitative measurement of these process have many
application in preformulation study including Purity,
Polymorphism, solvation, degradation

26. • Crystalline materials gives characteristics pattern – by
peaks in certain position & varying intensities.
• different Polymorphs – different x-ray diffraction pattern
due to crystal lattice. Single crystal x-ray analysis
provides precise identification & description of a
crystalline substances.