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CHEMICAL STABILITY
OF DRUGS
TOMMY JULIANTO
FACULTY OF PHARMACY
UNIVERSITI TEKNOLOGI MARA
Chemical decomposition of
drugs
Type of the main decomposition process.
Conditions of drugs in both liquid and solid
formulations can loss their potency.
T be
To
b aware to
t some chemical
h i l groups
which when present in drug molecules can
cause stability problem.
How to minimize the chemical breakdown.
Hydrolysis
Drugs are susceptible to this type of
degradation:
Examples of chemical
groups susceptible to
hydrolysis. :
Oxidation
Oxidation is the next common pathway for
drug breakdown and the process usually
control by the environment.
E.g. light, trace metal, oxygen and oxidizing
agent.
there are little attention on oxidation
simultaneous hydrolitic and oxidative
degradation also can occur
Autooxidation
Isomerisation
Process of conversion of a drug into its
optical or geometric isomers.
May regarded as a form of drug degradation.
Often resulting in a serious loss of
therapeutic activity.
Adrenaline in solution form at low pH has
been attributed to racemination that lead to
loss of activity. Conversion of the
therapeutically active form, from laevolaevo-rotary
form into its less active isomer.
Photochemical decomposition
(Photolysis)
Light is often catalised oxidation and hydrolysis
When molecules are exposed to electromagnetic
radiation they absorb light (photons) at
characteristic wavelengths
g
which an increase in
energy, which can:
- cause decomposition
- be retained or transferred
- be converted to heat
- result in light emission at a new wavelength
(fluorescence, phosphorescence)
Polymerisation
The process by which two or more
identical molecules combine together to
form a complex molecule.
Concentrated aqueous
q
solution of
ampicillin sodium
The reactive -lactam bond of ampicillin
molecule is opened by reaction with the
side--chain of a second ampicillin molecule
side
and a dimer is formed > higher polymer.
Temperature
Influence of pH
The degradation of most drugs is catalysed
by extreme pH.
Solvolysis
Chelating agents
Hygroscopicity
Solid--state stability
Solid
ORDER OF REACTION
Solid
- Heat (
(C); 4, 20, 30, 40, 40/75% RH, 50 and 75.
- Moisture uptake; 30, 45, 60, 75 and 90% RH at
room temperature.
- Physical stress; ball milling.
Aqueous solution
- pH; 1, 3, 5, 7, 9 and 11 at RT and 37 C. Reflux in 1
M HCl and 1 M NaOH.
- Light; UV (245 and 366 nm) and visible at RT
- Sparging with oxygen at RT; UV.