DRUG STABILITY

Ungsari Rizki Eka P., M.Sc., Apt.

STABILITY ------- QUALITY
 Main Categories of Drug Stability
Category Description Examples
Chemical Stability Breakage or formation of Ester hydrolysis
covalent bonds resulting in, Amide hydrolysis
for example, loss of
potency. Lactam hydrolysis
Oxidation
Physical stability No breakage or formation Christallization of
of covalent bonds. Such amorphous drug
change can lead to changes Change in crystal form
in drug solubility or change
in the appearance of the Loss of crystal water
drug product.
Microbial stability Microbial contamination Aqueous eye drop
Parenteral solution
 Classification of Drug Degradation
According to the Drug Product Form
Form Description Examples
Solution One liquid phase Parenteral solutions
Hydrogels
Ointments
Suspension One solid and one liquid Oral suspensions
phase Eye drop suspensions
Emulsion Two liquid phase Creams
Solid oral dosage form One or more solid phases Tablets, capsules
 The rate of reaction may be defined as the rate of concentration
changes of the reactants or products :

a.A + b.B  P
where a and b represent number of molecules, A and B the
reactants, and P the product.
The rate is expressed as 2d[A]/dt, 2d[B]/dt, and d[P]/dt, where t is
the time and [A], [B], and [P] represent concentrations.
The order of reaction is the sum of a and b (i.e., the number of
molecules participating in the reaction). For example, hydrolysis of methyl
salicylate in aqueous solution follows the chemical equation :

where methyl salicylate and water are the reactants and salicylic acid and
methanol the products.
 DEGRADATION
PATHWAYS
3
1
HYDROLYSIS OXIDATION

5
DECARBOXYLATION
2 6
DEHYDRATION
PHOTOLISIS 4
7
POLYMERIZATION ISOMERIZATION
 TUGAS KELOMPOK
1 kelompok : 3 mahasiswa
Cari jurnal yang membahas jalur degradasi obat
sesuai tema pada slide sebelumya.
Dibaca, dipahami, direview (dibahas),
diketik, dicetak
PENGUMPULAN : 2 MINGGU SETELAH
PERTEMUAN HARI INI
Presentasi 2-3 kelompok per pertemuan
Presentasi dan tugas yang baik akan dibebaskan
mengikuti KUIS dengan nilai 85.
 DEGRADATION PATHWAYS
HYDROLISIS
Hydrolysis indicates cleavage of chemical bonds by the addition of
water. Hydrolysis is one of the most common drug degradation reactions,
even in solid dosage forms in the presence of moisture, and the most
common substrates are those that contain the acyl group:
 DEGRADATION PATHWAYS
HYDROLISIS

Example :

HYDROLYSIS OF HOMATROPINE
IN AQUEOUS SOLUTION ??
 HYDROLYSIS OF HOMATROPINE IN AQUEOUS SOLUTION ??

Homatropine is an ester that undergoes hydrolysis in aqueous solutions.

Samples were collected and the homatropine concentration at various time
points calculated:

Time (h) [Homatropine] (M) Ln [Homatropine] (M)

1.4 0.026 ?
3.0 0.024 ?
6.0 0.021 ?
9.0 0.018 ?
12 0.015 ?
17 0.012 ?
The following values can then be

calculated from the graph:

The first-order rate constant = k1 = ?

The half-life = t1/2 = ?

The shelf-life = t90 = ?

 PUSTAKA
• Loftsson, Thorsteinn. 2014. Drug Stability for Pharmaceutical
Scientists. USA : Elsevier Inc.