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Stabilitas padatan
Fisika
Transformasi Polimorfik
Kristalisasi, perubahan bentuk polimorf, interaksi
dengan eksipien, interaksi dengan lembab,
kontaminasi.
Kimia
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Stabilitas fisika
Stability of amorphous form
greatly depends on how is it prepared.
Crystallization above Tg
Presence of residual crystallinity (defect sites)
can be source for nucleation
In general, grinding/milling produces least stable
amorphous form
Stabilitas fisika
Stability of the crystalline state
Polymorphic transformation and solvation/desolvation
biggest problems
Stability of polymorphic form may depend upon
temperature
Presence of moisture can promote polymorphic and
pseudopolymorphic transformations
Polymorphic and pseudopolymorphic changes are often
observed upon scaling up a process
Stabilitas kimia
Stability of amorphous form
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Stabilitas kimia
Stability of the crystalline state
Four steps to a solid-state reaction
1. Loosening of molecules at the reaction site necessary distortion of reaction cavity
2. Molecular change - breaking and forming of
chemical bonds
3. Solid-solution formation - reactant and product
both present in crystal
4. Separation of product - production of new
product crystals
.Molecular mobility can be enhanced by presence
of defect sites
.Common reactions in the solid state include
hydrolysis, oxidation, and photolysis
Stabilitas kimia
Equations
Relating to
Decomposition
in the Solid
REACTION KINETICS
SIMPLEST DECOMPOSITION MODES OF
PURE SOLIDS
Solid is placed in a vacuum &
exposed by temperature
I
II
III
IV
V
VI
Faktor-faktor yang
mempengaruhi degradasi
obat padat
Kelembaban
2. Eksipient
3. Kekerasan tablet
4. Material kemasan
1.
The
Crystallization of Amorphous
Drugs
Attempts
Polymorphism/Transitions in Crystalline
States
Polymorphs
same drug.
Because these forms have different free energy
or chemical potentials, depending on
temperature conditions, transitions between
polymorphs occur.
Polymorphic transitions during storage may alter
critical properties of drugs because the solubility
and dissolution rate of drug substances
generally vary with changes in their crystalline
form.
From a storage perspective, temperature and
humidity affect polymorphic transitions.
Polymorphism
Many
The
The
mechanism
water
The
Water
Effect
Moisture Adsorption
Moisture
Effect of excipients
Examples:
Excipients
excipients
Eksipient
Beberapa
eksipient dilaporkan
meningkatkan kecepatan degradasi
seperti :
Talcum :
Mg
Stearat :
mempercepat perubahan
warna pada tablet yang
mengandung amina dan
lactose
Asam
stearat dan
kalsium
suksinat
meningkatkan degradasi
tablet aspirin
moisture.
For example, owing the high moisture content of
polyvinylpyrrolidone and urea, aspirin hydrolysis was
enhanced in solid dispersions with these excipients
Decreased drug stability caused by excipients having
higher moisture-containing ability has been reported
for tablets of aspirin and ascorbic acids
Degradation of ascorbic acid in the presence of silica
gel increased with increasing water content
The higher degradation rate observed in the presence
of silica gel compared to that for ascorbic acid alone at
the same moisture content suggested an accelerating
effect of silica gel itself or of one of its impurities
Other Properties of
Excipients
Excipients
Miscellaneous Factors
Excipients
Miscellaneous Factors
Vapor-Phase Transfers
Including Sublimation
Pharmaceuticals
containing components
that sublime easily may undergo changes in
drug content owing to the sublimation of
the drug substances or excipients.
In the case of nitroglycerin, which is a liquid
with a significant vapor pressure, sublingual
tablets exhibited significant variations in
drug content during storage owing to inter
tablet migration through the vapor phase
This transfer was inhibited by adding watersoluble nonvolatile fixing agents such as
polyethylene glycol.
Kinetics of Solid-Phase
Transitions
The
Effect of Packaging on
Stability of Drug Products
primary
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