Biomedical Engineering Reference
In-Depth Information
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3.2.P.4: Control of Excipients
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3.2.P.5: Control of Drug Product
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3.2.P.6: Reference Standards or Materials
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3.2.P.7: Container Closure System
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3.2.P.8: Stability
Final product release specifications are developed on drug product
characteristics and container closure system used. Ophthalmic prod-
uct quality tests were classified into two general categories namely,
universal and specific tests as per USP [
1
]. If necessary, often perfor-
mance tests may be included into test and specification to sustain
quality. Universal tests consist of active assay, impurity analysis, preser-
vative assay, pH, osmolality, appearance, particulate matter, sterility,
bacterial endotoxin, etc. Specific tests include particle size, viscosity,
drop size, etc. Acceptance criteria of release specifications are based on
target product profile, regulatory guidance, route of administration,
and dosing posology. Shelf life specifications are always developed
based on real time data in final packaging. If adequate real time data
is not available, stress stability results may be used as per guidance of
regulatory agencies.
5.1 Control of Drug
Products (Tests)
A qualitative description of dosage form as to how it should appear
is a part of acceptance criteria of DP. While it is straightforward for
suspension, ointment, and emulsion dosage forms, solution appear-
ance test consists of four individual tests, namely, color, clarity,
particulate, and precipitate tests. Visual observation should indicate
solutions to be essentially particle free.
5.1.1
Universal Tests
Product Description
(Appearance)
Tolerability of ocular formulation to ocular tissues without causing
any considerable irritation is observed in pH ranges 4-8. However,
most of the marketed formulations are formulated at a pH from 5
to 8. This is a critical quality test for all ophthalmic formulations
except ointment. Formulation pH drift should be studied well to
set specification that would allow desired shelf life. Drift of pH in a
well-buffered formulation is usually insignificant. A pH drift may be
associated with leachable from packaging or from degradation of
one component in the formulation. Buffer capacity of the formula-
tion should be kept as such that it does not induce irritation. Test
for pH is usually conducted according to USP
pH
791
.
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>
Ocular tissues can tolerate ophthalmic preparation with a wide
range of osmolality ranging from 160 to 480 mOsm/kg
corresponding to 0.5-1.5 % sodium chloride concentration. How-
ever, it is prudent to develop formulation as close as possible to
isotonic (equivalent to 0.9 % sodium chloride concentration). This
will assure comfort and tolerability of the product. Osmolality test
is routinely performed using freezing point osmometer.
Osmolality
