Stability studies ensuring the maintenance of product quality, safety and efficacy throughout the shelf life are considered as pre-requisite for the acceptance and approval of any pharmaceutical product. Stability testing is a routine procedure performed on drug substances and products and is employed at various stages of the product development.

1. M.Pharm 1st Semester Seminar
Subject : Formulation Development
Topic : Solid State Drug Stability
By:
Anindya Jana
M.Pharm 1st Year (Pharmaceutics)
Regd. No. : 1661611006

2. Introduction
Stability of pharmaceutical product may be
defined as the capability of a particular
formulation, in a specific container/closure
system, to retain its physical, chemical,
microbiological, therapeutic & toxicological
specification.

3. Types of Stability & Condition Maintained
Throughout The Self Life of The Drug Product
Stability
Chemical
Therapeutical &
Toxicological
Microbiological
Physical

4. Factors Influencing Drug Stability
The degradation of
pharmaceutical product
can be treated as zero
order reaction, first order
reaction or pseudo order
reaction.

5. (1) Zero Order Reaction
The reaction rate is independent of concentration of the reacting substance.
Mathematically,
Rate of concentration decrease =
-dCa / dt = k (I)
Where,
Ca = concentration of reacting material.
k = Proportionality Factor
T = Time
Since Ca is a constant, X, the amount of
reacting, is identified as
dx / dt = k (II)
Integration of equation (II) yields
x = kt + constant

6. (2) Pseudo Zero Order Reaction
In solid state, many drug decomposes according to
pseudo zero order reaction rates, as reaction occurs
between the drug and moisture in the solid dosage form.
The system behaves as a suspension, & because of the
presence of excess solid drug, the first order reaction rate
becomes a pseudo order reaction rate, & the drug loss
rate is linear with time.

7. (3) First Order Reaction
The rate of reaction is directly proportional to the concentration of the reacting
substance.
Mathematically,
Rate of concentration decrease =
_dCa / dt = kCa (I)
Integrating eq (I)
-dCa / Ca = kdt (II)
We obtain,
-lnCa = kt + i (III)
Where i is the constant of integration converting
from natural logarithm (ln) yields
-log Ca = kt/2.303 + constant

8. (4) Influence of pH on Degradation
The magnitude of rate of hydrolytic reaction
catalysed by hydrogen and hydroxyl ions can vary
with pH .
Hydrogen ion catalysis predominates at lower pH
range.
Hydroxyl ion catalysis at higher pH range.

9. (5) Influence of Temperature on Degradation
In order for the rate constant or velocity of the degradation to be of use in the
formulation of pharmaceutical product, it is necessary to evaluate the
temperature dependency of the reaction.
The most satisfactory method for expressing the influence of temperature is given
by Arrhenius.
k = Ae-Ha/RT (I)
where,
k = specific rate of degradation
R = Gas constant (1.987 Calories degree-1 mole-1
T = Absolute Temperature
A = Frequency Factor
Ha = Activation Energy
After integration equation (I) becomes
log k2 / k1 = ∆Ha / 2.303R (1/T2 – 1/T1)

10. (6) Influence of Dehydration on Degradation
In physical dehydration processes water removal does not
create new bonds but often changes the crystalline
structure of the drug.
Since anhydrous compounds have different dissolution
rates compared to their hydrated, dehydration reaction
involving water of crystallization may potentially affect the
absorption rate of the dosage form.

11. (6) Influence of Optical Isomerization on Degradation
A Change in the optical activity of the drug may result as a change
in its biological activity. Racemization is its main type of optical
isomerization which effect drug molecule and it occurs when the
optical active form of the drug is converted into its enantiomorph.
Racemization continues until 50% of the original drug has been
converted into its enantiomorph.
In most cases the enantiomorph has less therapeutic effect than the
original drug.

12. (6) Influence of Hydrolysis on Degradation
 Drugs with functional group such as ester, amide,
lactones may be susceptible to hydrolytic
degradation.
 It is probably the most commonly encountered mode
of drug degradation because of the prevalence of
such group in medicinal agents and the ubiquitous
nature of water.

13. (6) Influence of Photolysis on Degradation
Photolysis is the process by which the light sensitive drug or
excipient molecules are chemically degraded by light, room light, or
sunlight. The variation of degradation depends on the wavelength
of light.
In this process, light may be initiator while the reaction may be
oxidation, polymerization or ring rearrangement.
Photolysis followed by a thermal reaction since light energy
converted into heat energy.

14. Stability of Tablet
 Stable tablet should retained their original size, shape, weight &
colour under normal handling and storage condition throughout
their self life.
 Excessive powder or solid particle at the bottom of the container,
cracks or chips in the face of tablet or appearance of crystal on
the surface of the tablet or container walls are indication of
physical instability of uncoated tablets.
 Tablet hardness or resistance to crushing or fracturing can be
assayed by commercially available hardness tester.

15.  Colour stability of tablet can be followed by an appropriate
colorimeter or refractometer with heat, sunlight and intense
artificial light employed to accelerate the colour deterioration.
 For making bioavaibility predictions, dissolution test gives more
meaningful results than disintegration test.
 Uniformity of water, odour, texture, moisture content and humidity
effects also studied during a tablet stability test.

16. Reference
 L. Lachman & H Lieberman; The Theory & Practice of industrial Pharmacy;
CBS Publishers & Distributors PVT LTD; 2009; P760-803
 J Carstensen, C Rhodes; Drug Stability Principles & Practice; Third Edison;
2008; P145-190
 Remington; The Science & Pharmacy Practice; 21st Edition; Volume 1; P 1025-
1038

17. Thank You