Basic calculations in pharmaceutical

analysis
By: Yehualashet T. (BSc, MSc. Of pharmaceutical Analysis & Quality Assurance)

1
 Cont…
 Quantitative calculations are common everyday practice for
pharmacists engaged in laboratory work.
 This lesson therefore aims at familiarizing students with
such calculations mainly done in pharmaceutical analysis.
 It exposes the reader to various approaches for problem
solving and aids in consolidating theoretical knowledge
by applying it to the solution of real problems.

2
 Expression of concentration

Percentage volume/volume (%v/v)

 It is most often encountered in relation to the composition of
mobile phases used in HPLC.
 It measures the concentration of a substance in a solution and
it is expressed as the ratio of the volume of the solute to the
total volume of the solution multiplied by 100.
 % v/v = mL of solute/100 mL of solution

3
 Cont…
 Example: What is the % v/v of a solution that has 5.0 mL
of hydrochloric acid (HCl) diluted to 100 mL with
deionized water?

4
 Percentage weight in volume (%w/v)

 It is used to express the content of active ingredient in

liquid

formulations such as injections, infusions and eye drops.

 It is calculated by dividing the mass of the solute in grams by the

volume of solution in millilitres then multiplying this by 100.

w/v (%) = mass of solute (g)
x100
volume of solution (mL)

Question 1. What is the weight/volume percentage concentration of 250 mL

of
aqueous sodium chloride solution containing 5 g NaCl?
5
 Percentage weight in weight (%w/w)

 used to express the concentration of active ingredient in a

formulation such as a cream or to express the content of a
minor impurity in a drug substance.

Example: Determine the percentage of a solution containing 25.0 g NaCl

dissolved in 100 mL deionized water.
Given: Solute mass (NaCl) = 25 g, Solvent mass (deionized water) = 100 g (1 ml deionized water
weighs about 1 g)
Required: mass% of NaCl
Solution: solution mass = solute Mass + mass of solvent = 100 g + 25 g = 125 g
Mass% of NaCl in this solution = (25 g / 125 g) 100% = 20%
Therefore, the mass% of NaCl in solution is 20%.

6
Molarity
The molar concentration (Cx) of the solution of the chemical
species X is the number of moles of that species that is
contained in one liter of the solution (not one liter of the
solvent).
The unit of molar concentration is molarity, M, which has the
dimensions of mol L-1.
Cx= no mole solute = no m mole

solute no L solution
no ml solution
7
 Examples
1. Suppose you had 0.2 moles of solute dissolved into 100 ml of solution.
What's the molarity of the solution?

2. Calculate the molar concentration of ethanol in an aqueous solution

that contains 2.30g of C2H5OH (46.07 g/mol) in 50L of solution.

3. Suppose you had 58.44 grams of NaCl and you dissolved it in

exactly
2.00 L of solution. What would be the molarity of the solution?

4. How many grams of KMnO4 (158g/mol) are needed to make 500.0

mL
of a 0.200 M solution?
8
Normality

⚫ Normality (N) is defined as the number of equivalents of solute dissolved in one liter
of solution.
N= no of equivalent weight no of equivalent weight =

weight of solute Volume of so/n in Liter equivalent

weight

⚫ An equivalent weight is defined as the ratio of a chemical species’ formula

weight (FW) to the number of replacing units, n

⚫ The number of replacing units, n, is based on a reaction unit, which is that part of a

chemical species involved in a reaction

⚫ Normality makes use of the chemical equivalent, which is the amount of one
9
chemical species reacting stiochiometrically with another chemical species.
 Dilutions
 It is the process of decreasing the concentration of a stock solution by

adding more solvent to the solution

 Frequently, solutions with very low concentrations are used in

pharmaceutical analysis

 To prepare very dilute solutions it is common to first make a

concentrated solution, and then to dilute this to a lower concentration

10
 Dilutions……..
 In order for an extract from a formulation or a solution of a pure drug
substance to be measured, it must be diluted so that it falls within
the working range of the instrument used to make the measurement.
 Thus an understanding of dilution factors is fundamental to
calculations based on analytical data.

11
 Calculation example

1. A 2 ml volume of eye drops containing the local anesthetic

proxymetacaine. HCl is diluted to 100 ml and then 5 ml of the dilution
is diluted to 200 ml. The diluted sample was measured by UV
Spectrophotometry and was found to contain 0.512 mg/100 ml of the
drug. Calculate the %w/v of the drug in the eyedrops.
Answer: Dilution factors 2 to 100 ( 50), 5 to 200 ( 40). Total dilution 40
x 50 = 2000.
Original concentration =2000x 0.512 = 1024 mg/100 ml = 1.024 g/100
ml = 1.024% w/v.

12
 Self test
2. A 5 ml sample of an injection of a steroid phosphate was diluted to 100 ml.
Then 10 ml of the diluted injection was diluted to 100 ml and this dilution
was further diluted 10 to100 ml. From measurement by UV the diluted
sample was found to contain 0.249 mg/100 ml of the steroid. What was the
original concentration of the injection in %w/v and in mg/ml? Answers:
0.498% w/v, 4.98 mg/ml
3. 50.0 mg paracetamol is dissolved in 100.0 ml methanol in a volumetric
flask. From this solution, 1.00 ml is picked up by a transfer pipette and
diluted to 100.0 ml with methanol in a new volumetric flask. What is the
concentration of paracetamol in the final solution?

Answer:
13
Physical and chemical properties of
drug molecules

14
 Physical and chemical properties of drug molecules

 Chemical analysis is an important part of the quality

assessment of drugs.
 The physical properties of drug molecules, along with simple
chemical derivatisation and degradation reactions, play an
important part in the design of analytical methods
 Drug molecules can be complex, containing multiple
functional groups that in combination produce the overall
properties of the molecule

15
 Cont.…
 A deeper understanding of the analytical method requires
knowledge about both the analytical technique and the
chemical properties of the analytes.
 Chemical and physical behavior of drug molecules, influence
the development of analytical methods.
 Here, the chemical and physical behavior of drug molecules
that influence the development of analytical methods.

16
 Cont.…
 most drugs used in medicine behave in solution as either weak acids
or weak bases.

The pKa and pKb values give information about the strength of
acids and bases; they tell you the pH at which 50% of the drug is
ionised.

Better to discuss pH, pKa and pkb

17
 How Do We Measure pH?

 For accurate
more
measurements, one uses a pH
meter, which measures the
voltage in the solution.

18
 pH
 The hydrogen ion concentration or pH is a measure of
the
acidity or alkalinity of a solution.
 In an aqueous solution, the product of hydrogen
ion concentration and hydroxyl ion concentration is constant.
 The pH of solution is defined as the negative logarithm of the
hydrogen ion concentration, in an aqueous solution

19
 Cont.…
 A pH meter is a scientific instrument that measures the
hydrogen-ion activity in water-based solutions, indicating its
acidity or alkalinity expressed as pH
 pH is the unit of measure that describes the degree of
acidity or alkalinity. It is measured on a scale of 0 to 14

20
 pH value of aqueous solutions

 Dissociation of water
 The pH of a solution is defined as –log [H+]

 pH = - log[H+] = log1/[H+]

[H+] is the concentration of hydrogen ions in solution.

Where Ka is the dissociation constant for the equilibrium , is known as Kw (

ion product of water) in case of the dissociation of water

pKw

= pH + pOH = 14

21
 Cont.…
 If an acid is introduced into an aqueous solution , the [H+] increases

 If the pH of an aqueous solution is known, the [H+] is given by the

expression 10-pH
 e.g. [H+] in pH 4 solution=10-4M=0.0001M

 Since [H+][OH]=10-14 for water, the concentration of [OH]

in this
solution is 10-10 M

22
 Strong acids and bases

 Strong acids and bases are completely dissociated in to

its
component ions in aqueous solution.
 The strong acid of its conjugated base are quite weak and
weak acid do not dissociate in water hence its conjugated base
exceedingly strong.

 The common strong acids are HCl, HClO4, HNO3, H2SO4 and
the common strong bases are NaOH, KOH

23
 Cont.….
 Calculate the pH of the following solutions:
i. 0.05 M HCl
ii. 0.05 M NaOH
iii. 0.05 M H2SO4.

Answered 1.3, 12.7, 1

24
 pH for weakly acidic and basic solutions
weak acid

 Weak acids and bases are those that are not completely dissociated in
aqueous solution and are in equilibrium with the undissociated acid.
 the extent of dissociation is characterized by Ka
 Consider weak acid HA in a solution at total solute concentration of C
 The dissociation reaction is HA Ka H+ + A
- Ka = [H+][A-] / [HA]
 Not completely dissociates, [H+] is less than C
Ka
 HA H+ + A- ,[H+] = [A-], [HA] = c – [H+], [HA] is
undissociated one

25
 Cont.….
 Ka = [H+]2/(c - [H+]), if weakly dissociated, c -
[H+]~ c

 [H+] = (KaC)1/2 , pH = -1/2 log(KaC)

 Example: what is the pH of 0.1M acetic acid (Ka = 1.75 x 10-5) ?

26
 Weak acids…..

In comparison the pH of 0.1 M HCl is 1.

27
 Weak bases
 The calculation of the pH of a weak base can be considered in the same
way as that of weak acids
 The dissociation reaction for a weak base, B, may be written as:
Kb
B + H2O BH+ + OH- Kb = [BH+][OH-] / [B]
 Let the total solute concentration be C
 Kb = [OH-]2 / (C - [OH-]) Kb = [OH-]2 / C

 [OH-] = (KbC)1/2 [H+] = Kw / [OH-] = Kw / (KbC)1/2

28
 Weak base……….

• Example: what is the pH of 0.1M solution of ammonia

(Kb=1.8 x10-5)?

In comparison, the pH of 0.1 M NaOH is 13

29
 Self test
Calculate the pH of the following solutions:
i) 0.1 M HCOOH or formic acid (Ka = 1.77 x 10-4)

ii) 0.05 M phenol or C6H5OH (Ka = 1.3 x 10-10)

iii) 0.15 M ethylamine or CH3CH2NH2 (Kb = 5.6 x 10-4)

30
 Factors Affecting Acid Strength

 The more polar the H-X bond and/or the weaker the H-X bond, the
more acidic the compound.
 Acidity increases from left to right across a row and from top to bottom
down a group.

31
 Buffers

 are used to maintain the pH of a solution in a narrow range.

 Human plasma is buffered at pH 7.4 by a

carbonic acid/bicarbonate buffer system.
 are used in the preparation of mobile phases for chromatography and
the extraction of drugs from aqueous solution.
 The most effective range for a buffer is 1 pH unit either side of the
pKa value of the weak acid or base used in the buffer.
 The pKa value of acetic acid is 4.76; thus its effective buffer range is
3.76–5.76.

32
 Buffer cont…
 The simplest type of buffer is composed of a weak acid or base in
combination with its conjugated a strong base or acid.
A common buffer system is the sodium acetate/acetic
acid buffer
system.
 The most direct way of preparing this buffer is by the addition of
sodium hydroxide to a solution of acetic acid until the required pH is
reached.
pH of buffer is solution determined from Henderson–Hasselbalch equation
Buffer of weak acid and its salt:

Buffer of weak base and its salt:

33
 How a Buffer Works
Consider adding H3O+ or OH- to water and also to a buffer

For 0.01 mol H3O+ to 1 L water:

[H3O+] = 0.01 mol/1.0 L = 0.01 M pH = -log([H3O+]) =
2.0

So, change in pH from pure water: dpH = 7.00 – 2.00 = 5.0

For the H2CO - / HCO - system:

3 3
pH of buffer = 7.38
Addition of 0.01 mol H3O+ changes pH to 7.46

So change in pH from buffer: dpH = 7.46 – 7.38 = 0.08 !!!

34
 The Henderson-Hasselbalch Equation

 Anequation that could calculate the pH value of a given

buffer
solution.
 It wasfirst derived by the American chemist Lawrence
Joseph
Henderson.
 This equation was then re-expressed in logarithmic terms by
the Danish chemist Karl Albert Hasselbalch.
 The Henderson-Hasselbach equation is derived from the definition
of the acid dissociation constant as follows.
 Consider the hypothetical compound HA in water.
35
Cont….

36
Cont….

37
 Cont….
 Suppose we are making a buffer solution of ammonium
(NH4+) and ammonia (NH3). In this example, ammonium is
our weak acid and ammonia is the conjugate base. The
reaction is as follows.

 If the pKa of ammonium is 9.3 and we want a pH of 10. What

ratio of ammonia to ammonium should you add to the
solution?

38
 Cont…

 Therefore, the ratio is about 5 times the amount of ammonia as

ammonium to get a buffer solution with a pH of 10.

39
Problem:
Calculate the pH of a solution containing 0.200 M NH3
and 0.300 M NH4Cl given that the acid dissociation
constant for NH4+ is 5.7x10-10.

NH3 + H2O  NH4+ + pKa = 9.244

Ka
OH -
base acid

[B] pKa applies

pH  pKa  to this acid
log [BH ]

(0.200)
pH = 9.244 + log
(0.300)
pH = 9.07
40
 Limitation of HH
 When using the Henderson-Hasselbalch to make a buffer solution the
ratio should be close to one.
 This makes the most stable solution.

 When the ratio moves far away from one, the capacity to buffer the
solution decreases as a small disturbance changes the pH dramatically.
 The Henderson-Hasselbalch equation does not provide accurate pH
values for extremely dilute buffer solutions because it does not account
for the self-dissociation that occurs in water.

41
 Limitation….
 If an acid can easily dissociate more than one hydronium ion
(H+) the equation does not account for that and may not work
well.
 The Henderson-Hasselbalch equation cannot be used for
strong acids and strong bases

42
 Ionisation of drug molecules
 When a weakly acidic or basic drug is administered to the body, the drug will
ionize to a greater or lesser extent depending on its pKa and the pH of the body
fluid in which it is dissolved.
 The pH of the body varies widely, but the most important biological solution is
the blood, normally has a pH of 7.4.
 The ionisation of drug molecules is important with regard to
 their absorption into the circulation and
 their distribution to different tissues within the body
 Drugs are better absorbed in unionized form.

 Non-ionized=lipid soluble=absorbed well

 The pKa value of a drug is also important with regard to

 the design of analytical methods for its determination
 Ionized=water soluble
43
 Cont…
 The percentage of ionisation for an acid or base of a
particular pKa value at a particular pH value is:

44
 Example:
1. Calculate the percentage of ionisation of the drugs shown in Figure
below, at pH 7.0.

45
Example………..

46
Example 2:

47
Drug stability

48
 Drug stability
 Drug stability means the ability of the pharmaceutical dosage form to
maintain the physical, chemical, therapeutic and microbial properties
during the time of storage and usage by the patient
 The purpose of drug stability testing is:
– to provide evidence on how the quality of a drug
substance or drug product changes with time under the influence
of environmental factors such as temperature, humidity and light.
 The aim of the testing is to

– establish the shelf-life of a product and recommended

storage
conditions. 50
 Instability may cause
 Undesired in performance, i.e.
change
dissolution/bioavailability
 Substantial changes in physical appearance of the dosage
form
 Causing product failures

50
 Factors affecting Stability
1- Environmental factors : -
Temperature Light , Oxygen, Moisture &
2
Carbon
Drugsdioxide
or excipients in the dosage form: Particle size
of drug & pH of the vehicle
3 Microbial contamination

4 Trace metal Contamination

5- Leaching from containers

51
 Stability is used to determine
 Quality of a drug substance or drug product
 Shelf life for the drug product
Recommended storage conditions
Why stability testing is necessary :
 Chemical degradation may lead lowering of concentration
of drug in dosage form
 toxic product may form due to degradation of
active ingredients

52
Cont….

53
 Types of stability

 Three stabilities of drug must be considered:

1. Physical stability
2. Chemical stability
3. Microbiological stability

54
 A. Physical stability
 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:
 pharmaceutical elegance
 drug content uniformity
 drug release rate.

55
 Types of physical degradation are

1. Loss of volatile components

2. Loss of H2O

3. Absorption of H2O

4. Crystal growth

5. Polymorphic changes

6. Color changes

56
 1. Loss of water
This can be seen in the following dosage forms:
a. Emulsions: Loss of water lead to separation of the two phases and change to

other type

b. Creams: especially oil/water, they become dry by loss of water

c. Ointments: especially aqueous base ointments

 Humectants is added to the previous dosage forms which defined as hydrophilic

substances added to aqueous phase to absorb water from atmosphere and prevent

its loss from the dosage forms. Examples: Glycerin

57
 2. Crystal formation
 Crystal formation in pharmaceutical preparations: Causes:

a. Polymorphism phenomena: i.e. Chloramphenicol (change of

amorphous to crystalline form.

b. Saturated solution: by different temperature precipitation of

solute may occur.

c. In suspension: when very fine powder is used a part

of suspending agent will dissolve then precipitate as crystal.

58
 3. Colour Changes:
Colour changes are of two types.
1. Loss of color due to PH change , Presence of reducing agent
2. Development of color · Exposure to light
Preventive measures for physical instability
 Loss of volatile components, Loss
of water & Absorption of
water:
Products should be placed in well-closed
 For solutions: Stabilizers are added
container.

 Crystal
For suspensions · Minimum
growth: flocculation should be
temp. Incorporation of surface active managed,

agent ·
 Color By increasing viscosity
changes: PHof should
suspendingnot be Exposure to light should be
material
changed
avoided and, An attempt has been made to prevent the fading by incorporating UV light
absorbing material.
59
 B. Chemical stability:
 It implies lack of any decomposition in the chemical moiety
that is incorporated in the formulation as the drug,
preservatives or any other excipients
 If any decomposition occur, it may influence the physical
and chemical stability of the drug

60
 Types of chemical degradation are as under

 Chemical degradation due to hydrolysis, Oxidation,

De-
carboxilation, Isomerization,
and
Polymerization Complexation or chelation.
 The ability of the drug remain within its chemical form under
various environmental condition.

61
 i. Hydrolysis
 “It is defined as the reaction of a compound with water.”

 Major cause of degradation of drug

 Factors Effecting Hydrolysis:

 Moisture
PH
Temp
Type of the solvent

62
Some Functional Groups Subject to Hydrolysis
Drug type Examples
Esters Aspirin, alkaloids
Dexmethasne sodium phosphate
Nitroglycerin
Lactones Pilocarpine
Spironolactone
Amides Chloramphenicol

Lactams Penicillins
Cephalosporins
64
 Hydrolysis Preventive Measures:
 Adjustment of pH: Rate of decomposition is critically
dependent Upon pH.
 Choice of solvent

 Addition of surfactants

 Modification of chemical structure

65
 ii. Oxidation
Oxidation of a compounds is explained is defined as loss
of electrons or gain of oxygen.

Some Functional Groups Subject to Autoxidation

Functional group Examples
Catechols Catecholamines (dopamine)
Ethers Diethylether

Thiols Dimercaprol (BAL)

Thioethers Chlorpromazine
Carboxylic acids Fatty acids

66
 Factors lead to oxidation
 Presence of oxygen, Light (It can cause photo-chemical reaction, i.e. chemical reaction

occur in presence of light.

 Temperature: Elevated temperature accelerate oxidation reaction

 PH : each drug has its ideal pH for stability. Any change in pH affect drug stability and

may accelerate oxidation reaction.

 Pharmaceutical dosage form; Oxidation reaction occur in solutions faster than in solid

dosage forms.

 Type of solvent used : Oxidation reaction occur faster in aqueous solution than others.

 Presence of unsaturated bonds : as double and triple bonds (oils) which undergo easier

than saturated bonds for oxidation.

66
 Protection of drugs from oxidation
 Addition of Antioxidants and inorganic sulfur compounds: Vitamin E,
Vitamin C, thio sulfate and polysulfide
 Addition of chemicals which form complexes with metals: EDTA,
Benzalkonium chloride
 Protection from light: Using of dark container , Storage in dark
places ,
Packaging with substances which absorbed light i.e. Oxybenzene
 Choice of suitable pharmaceutical dosage forms which reduce the
possibility of oxidation process (solid dosage )
 Maintenance of pH by using buffer solution and choice of
suitable solvent(rather than water)
 Storage in low temperature and protection from air by: using good
closed 67
 iii. Polymerization
 In polymerization, small repeating units called monomers are
bonded to form a long chain polymer.
 Ampicillin in high temperature forms polymers which
cause allergy

68
 Factors induce Polymerization

1. Temperature
2. Light
3. Solvent
4. pH
5. Impurities

69
 Iv. Isomerization
 It means conversion of drug to its isomer

 Isomers have Identical molecular but posses a

formulas different arrangement of atoms.

 reading assignment
1. Optical isomerization
2. Geometric isomerization

70
 C. Microbiological stability
 Microbiological stability implies that: formulation has not
suffered from any microbiological attack and is meeting the standards
with respect to lack of contamination/sterility.

 In the type of hygienic manufacture carried out today where

“Quality Assurance” is a prerequisite as per the GMP
procedures, there are definite procedures to prevent microbial
contamination in all formulations.

71
 CONT…
 Sources Microbial Contamination: Water, Air, Raw
materials,
of containers and closures, Personnel & Instruments
and apparatus
 To prevent contamination to the formulation during storage
1. suitably designing the containers

2. usually using single dose containers

3. sticking to proper storage conditions

4. adding an antimicrobial substance as preservative.

72
Stability Testing

73
Stability: is the capacity of product to remain
drug within
specification established to ensure its identity, strength, quality,
and purity

Stability is the study of the extent to which the

study: of a drug substance or drug product remain
properties
within
specified limits at certain temperature and humidity

74
 Stability Testing
 Provide evidence as to how the quality of the drug
product
varies with time.
 Establish shelf life for the drug product
 Determine container closure system suitability

 determine recommended storage condition

– Temperature and humidity
– advising patient on storage conditions
75
 Advantages of Stability studies
 Assurance to the patient
 Economic considerations
 Legal requirement
 Many drugs are quite stable, but functional groups such as:
– esters and lactam rings, which occur in some drugs, are
susceptible to hydrolysis,
– catechols and phenols are quite readily oxidised.
 The most common types of degradation which occur in pure and
formulated drugs obey zero- or first-order kinetics.

76
 Order of reaction
 Refers to the way in which the concentration of the reactant (s)
influence the rate of a chemical rxn.

1. Zero-order degradation
 Zero order rxn: the rate of rxn is independent of
the concentration of the reactants and constant with respect to
time

77
 Zero-order degradation
 In zero-order kinetics the rate of degradation is independent of
the concentration of the reactants.
 Thus, if the rate constant for the zero-order degradation of a substance is

0.01 moles h-1, then, after 10 h, 0.1 moles of the substance

will be degraded.
 This type of degradation is typical of hydrolysis of drugs
in
suspensions or in tablets.
 where the drug is initially in the solid state and gradually dissolves at
more or less the same rate as the drug in solution is degraded, i.e. the
equilibrium concentration in free solution remains constant. 78
Rate is constant

 where dC is the change in concentration wrt change in time t

 minus sign indicates that the concentration is decreasing

79
 Mathematically
 where k0 is the zero-order rate constant [concentration(C)/time(t)].

 The integrated and more useful form of the equation:

 The half-life equation for a zero-order reaction:

EXAMPLE 1
 A drug suspension (125 mg/mL) decays by zero-order kinetics
with a
reaction rate constant of 0.5 mg/mL/ hour. What is the concentration of intact
drug remaining after 3 days (72 hours), and what is its t1/2?
C=kot + Co
C = −(0.5 mg/mL/hour) (72 hour) + 125
mg/mL C = 89 mg/mL after 3 days
t½=1/2 Co /ko
t½ = 1/2 (125 mg/mL)/(0.5 mg/mL/hour) 80
• EXAMPLE 2
– How long will it take for the suspension to reach 90% of its
original concentration?

– Shelf-life: is the period at which the drug remains to its 90%

81
 First-order degradation

• First-order kinetics of drug degradation have been widely studied.

• This type of degradation would be typical of the hydrolysis of a drug

in solution..
• In first-order kinetics the rate constant k has the units h-1 or s-1 and
the rate of the reaction for a drug is governed by the expression:

82
83
 EXAMPLE 3

• An ophthalmic solution of a mydriatic drug at 5 mg/mL exhibits first-order

degradation with a rate of 0.0005/day. How much drug will remain after
120 days, and what is its half-life?
ln C = −(0.0005/day) (120) + ln (5 mg/mL)
ln C = −0.06 + 1.609
ln C = 1.549
C = 4.71 mg/mL
t½ =
0.693/0.0005/day
t½ = 1,386 days

84
85
Stability protocol

86
 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 at least six months and it
suggests sampling points of 0, 3, 6 months.

87
 Accelerated stability testing
 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 and Light

88
Thank you

89