Biomedical Engineering Reference
In-Depth Information
Terminal sterilization can be accomplished by moist heat or by
exposure to gamma radiation of suitable intensity. Although this
is most preferred, due to stability issues of DP and container
closure systems, often this method possesses technical challenges
and could not be realized.
l
Aseptic processing: This would require very tight control on
environment used in manufacturing product. Usually the formu-
lations are prepared in an environmentally sealed vessel and ster-
ilized (such as sterile filtration, autoclaving) prior to filling. For
suspension products, however, autoclaving can induce many
changes in formulation characteristics including crystal form
change of DS, agglomeration, particle morphology, particle size,
and particle size distribution. Therefore, often the DS is sterilized
(and may be micronized) first and then is mixed aseptically with
the other part of vehicle which was presterilized. This process
allows avoiding exposure of DS particle to high temperature.
Various topics and reviews on sterile product manufacturing are
available in literature [
51
,
52
].
Topical ophthalmic formulations (solution, gels, and suspensions)
contain
5.3 Typical Stability
Study and Protocol
95 % water as formulation vehicle and are packaged in
semipermeable plastic containers. Table
11
provides a stability
guideline for conducting stability study.
It should be noted that stability study should be designed by
keeping characteristics of drug substance, drug product, and QTPP
in mind. The stability study should be carried out in final packag-
ing. Table
11
provides a guideline only and should be modified
depending on the situation by including additional storage condi-
tion and timepoints.
>
Table 11
A general guideline to develop stability protocol for ophthalmic
formulations
Storage condition
Pull time (week)
Comment
20
C
1
Excursion criteria
5
C/35%RH
26, 52
NA
25
C/40 % RH
13, 26, 39, 52, 78, 104 Standard condition
30
C/65 % RH
13, 26, 39, 52, 78, 104 Intermediate condition
40
C/
<
25 % RH
6, 13, 26
Accelerated condition
55
C
1
Excursion criteria
Cycle (5
C/25
C)
-
NA
Cycle (
20
C/30
C) -
NA
Light (ICH condition) 6
NA
