Sie sind auf Seite 1von 94

Pengembangan produk

T N Saifullah Sulaiman
Lab. Teknologi Farmasi
Fak. Farmasi UGM
Raw Material Specifications
QbD is a systematic approach to
development that begins with
predefined objectives, and
emphasizes product and process
understanding and process control,
based on sound science and quality
risk management.
QbD requires an understanding of
how formulation and process variables
influence product quality.

For example, under QbD, the

specifications for raw materials, in-
process controls, and finished products
are established based on mechanistic
understanding of how formulation and
process factors impact product and
process performance, while ones under
QbT are derived empirically from limited
batch data
Bergstrom et al. in 2003 devised a modified
Biopharmaceutical Classification System, in
which they
categorized the drugs into six classes based on
the solubility and permeability. The solubility
was classified as "high" or "low" and the
permeability was allotted as "low",
"intermediate," or "high".
Excipient compatibility
The selection of excipients is vital in the design
of a quality drug product.

Excipients and their concentration in a

formulation are selected based not only on their
functionality, but also on the compatibility
between the drug and excipients.

An incompatibility may be defined as an

undesirable drug interaction with one or more
components of a formulation, resulting in
changes in physical, chemical, microbiological
Excipient compatibility studies are
conducted mainly to predict the
potential incompatibility of the drug
in the final dosage form.
These studies also provide
justification for selection of
excipients, and their concentrations
in the formulation as required in
regulatory filings.
An incompatibility in dosage form can
result in any of the following changes:

change in color/appearance;
loss in mechanical properties (e.g.,
tablet hardness)
changes to dissolution performance;
physical form conversion;
loss through sublimation;
a decrease in potency; and
increase in degradation products.
Stability to Support Product License
Packaging Selection for Dosage
Packaging is the economical
means by which a product is:
Protection is related to
1. Mojsture-As Liquid Water or Relative Humidity
( RH)
2. Gases
3. Light
4. Pressure (Atmospheric pressure)
5. Other Airborne Contamination
6. Printing and Decoration
Pack Selection
1. Product compatibility
2. Protection from environmental
condition to achieve the desired
shelf life
3. Package and product integrity
through the distribution channel
4. Resistence to children and
5. Government Role ?
Effect of Packaging on Stability of
Drug Products
1. Penetrasi
2. Pelunturan
3. Penyerapan
4. Reaksi kimia
5. Perubahan sifat-sifat fisik plastik atau
Gas, uap, atau cairan dpt. Berpengaruh
pada produk !
Adanya penetrasi hidrolisis dan
oksidasi Shelf life obat?
Temperatur dan kelembaban
faktor yang mempengaruhi penetrasi
oksigen dan uap air melalui plastik.
Pelunturan/ Leaching
Adanya migrasi komponen wadah ke dalam
produk, perusakan produk, kontaminasi,
efek toksik dll.

Perpidahan konstituen produk ke dalam
Mis. Zat aktif produk kecil produk tidak
Pengawet penyerapan produk
tidak terawetkan
Reaksi kimia
Adanya reaksi kimia antara
plastik dan produk akan
mengakibatkan perubahan
tampilan plastik dan produk obat.

Perubahan sifat-sifat fisik

plastik atau produk
Karena satu atau lebih sebab
dapat terjadi perubahan/modifikasi

The stages broadly associated with packaging

development are as follows:


All preformulation studies need some form of

container. It is therefore important to understand the
limitations associated with any packaging contact
material used to contain or retain the material under
test even at this very early stage of product
Product formulation

Formulations and any intermediates all

require to be contained and stored.
It is therefore necessary to make certain
that all packaging contact materials are
defined and that all pack parameters
(torque, heat seal etc.) are identified,
controlled and documented (all part of
good laboratory practice (GLP) and good
pharmaceutical manufacturing practice
(GMP) during formulation studies.
Formal stability tests

Normally three large-scale batches of

in each pack variant are stored at 25C and
60% RH
for long-term stability purposes, and at 40C
75% RH for accelerated stability, and
sampled over a
period of 5 years at examination intervals of
0 (initial), 3, 6, 9, 12, 18, 24, 30, 36, 48 and
months. The data generated are sent to the