Professional Documents
Culture Documents
SUGIYONO, APT
Instability
may cause
- Undesired change in performance, i.e.
dissolution/bioavailability
- Substantial changes in physical appearance of
the dosage form
- Causing product failures
PHYSICAL STABILITY
Physical
It is significant as it affects:
pharmaceutical elegance
drug content uniformity
drug release rate.
Likely physical
instability problems
Effects
Effects
Parenteral
solutions
Change in
appearan
ce and in
bioavailabilit
y
Likely physical
instability
problems
Suspensions 1- settling
2- caking
3- crystal growth
Effects
1-Loss of
drug content
uniformity in
different
doses from
the bottle
2- loss of
elegance.
Formulatio
n
Emulsions
Likely physical
instability
problems
1- Creaming
2- coalescence
Effects
1- Loss of
drug content
uniformity in
different
doses from
the bottle
2- loss of
elegance
Coalescence
Likely physical
Effects
instability problems
1. Changes in:
1-Loss of drug
content
a) Particle size
uniformity
b) Consistency
2. Caking or
coalescence
2- loss of
elegance
3. Bleeding
3-change in
drug release
rate.
Likely physical
Effects
instability
problems
Change in:
Change in
a) Disintegration time drug
release
b) Dissolution profile
c) Hardness
d) Appearance (soft
and ugly or
become very hard)
Likely physical
instability
problems
Change in:
a) Appearance
b) Dissolution
c) Strength
Effects
Change in
drug
release
CHEMICAL STABILITY:
Chemical
stability implies:
The lack of any decomposition in the chemical moiety
that is incorporated in the formulation as the drug,
preservatives or any other excipients.
This decomposition may influence the physical and
chemical stability of the drug
MECHANISMS OF
DEGRADATION
1- Hydrolysis:
Hydrolysis means splitting by water
Examples
Esters
Aspirin, alkaloids
Dexmethasne sodium phosphate
Nitroglycerin
Lactones
Pilocarpine
Spironolactone
Chloramphenicol
Penicillins
Cephalosporins
Amides
Lactams
Examples
Imides
Glutethimide
Malonic ureas
Barbiturates
MECHANISMS OF
DEGRADATION
2- Oxidation
Oxidation of inorganic and organic compounds is
explained by a loss of electrons and the loss of a
molecule of hydrogen.
Examples
Catecholamines (dopamine)
Diethylether
Dimercaprol (BAL)
Chlorpromazine
Fatty acids
MECHANISMS OF
DEGRADATION
3- Photolysis
MECHANISMS OF DEGRADATION
Relationship between wavelength and associated
energy of various forms of light.
Type of radiation
Wavelength
Energy
U.V.
Visible
I.r.
50 400
Kcal mol-1
400 750
287 72
750 10,000
36 - 1
MECHANISMS OF
DEGRADATION
Photolysis
is prevented by:
1- suitable packing in amber coloured bottles
2- cardboard outers
3- aluminium foil over wraps
1- pH
The acidity or the alkalinity of a solution has a
profound influence on the decomposition of drug
compound.
- Aspirin buffered solution is maximum stable at a
pH of 2.4, above a pH of 10 the decomposition rate
rapidly increases.
2- Light
Light sensitive materials are stored in ambered colour
bottles.
Oil systems
Ascorbyl palmitate
Butylaled hydroxy toluene
Butylated hydroxy anisole
MICROBIOLOGICAL STABILITY
Microbiological
Microbiological stability
Sources of Microbial Contamination:
Water
Air
Raw materials
Micrococci
Starches
Coliforms
Pigments
Salmonella
Actinomyces
Animal
products
Salmonella, Coliforms
Personnel
Coliforms, Staphylococci,
Sterptococci
2)
3)
4)
Preservative
Concentration(%w.
v)
0.5
0.3
0.1
Injections
Phenol
Cresol
Chlorocresol
Eye drops
Chlorhexidine
acetate
Benzalkonium
chloride
0.01
0.01
Mixtures
Benzoic acid
Methyl paraben
0.1
0.1
PRESERVATIVES USED IN
PHARMACEUTICAL
PREPARATIONS:
Preparatio
n
Preservative
Concentration(%
w.v)
Creams
Parabens
Chlorocresol
Methylparabe
n
0.1-0.2
0.1
0.1
Tablets
Glass
Overcome
use of Borosilicate glass
Masalah
corrosion
and