Pengembangan produk

T N Saifullah Sulaiman
Lab. Teknologi Farmasi
Fak. Farmasi UGM
Raw Material Specifications
PROCESS DESIGN, PROCESS OPTIMIZATION, AND SCALE-UP
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 or
therapeutic properties of the dosage form.
• 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.
SOURCES OF INFORMATION ?
Stability to Support Product License
Applications
Packaging Selection for Dosage Forms
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 tamperers
5. Government Rule ?
Effect of Packaging on Stability of Drug
Products
1. Penetrasi
2. Pelunturan
3. Penyerapan
4. Reaksi kimia
5. Perubahan sifat-sifat fisik plastik atau produk
 Penetrasi
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.

Penyerapan
Perpidahan konstituen produk ke dalam wadah
Mis. Zat aktif produk kecil produk tidak
manjur
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
 STAGES IN THE DEVELOPMENT OF A
PACK-PRODUCT COMBINATION

The stages broadly associated with packaging development are as

follows:

Preformulation

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
development.
 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 product

in each pack variant are stored at 25°C and 60% RH
for long-term stability purposes, and at 40°C and
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 60
months. The data generated are sent to the regulatory
authorities as part of the Marketing Authorization
Application.