Biomedical Engineering Reference
In-Depth Information
Table 4
(continued)
Test
Recommended target
Rationale for test
Comment
Drop size
a
As per QTPP
Usually 25-45
Control of container
closure system
Control of dosage
form administration
-
μ
L/drop
for topical ophthalmics
Weight loss
Preferably less than 5 %
at 40
C/26 weeks
Control of DP
Control of container
closure system
For information purpose
Developmental test
-
a
Not required for ointment
b
Not required for injectable products (IVT, intracameral, etc.)
Solutions are the most common dosage form for BCS class I and III
compounds or their suitable salts. Most of the currently marketed
ophthalmic products belong to this dosage form. The solution
dosage form has several advantages including dose uniformity,
ease of manufacturability and often provides better bioavailability.
The limitations with solution dosage forms is rapid clearance and a
short precorneal residence time after instillation. Additionally, solu-
tions of hydrolytically labile compound may have a limited shelf life
to have a marketable product.
Improvement of precorneal residence time after administra-
tion by reducing drainage can be improved by increasing viscosity
of the formulation [
38
-
40
]. For this purpose, synthetic, semisyn-
thetic, and naturally occurring polymers such as carbomer, polyvi-
nyl alcohol, povidone, hypromellose, other cellulose derivatives,
and guar gum were successfully used in various products [
41
].
According to current USP and work by Robinson [
39
] the corneal
residence time of active from topically applied formulation
increases proportionally with the increase of formulation viscosity
up to 20 cps. Potential disadvantages of high-viscosity solution
formulation include blurred vision and ocular discomfort; there-
fore attention should be paid before developing a high-viscosity
formulation.
For a solution formulation the drug concentration that can be
achieved is dependent on the pH solubility profile of the DS. If
needed the strength that can be achieved by increasing solubility
using suitable cosolvents and solubilizing systems. Low-dose
volumes, typically less than 50
4.1.1
Solution
L, are necessary for a product to
be appropriate for topical ocular administration. Selection of for-
mulation pH is driven by the drug substance's pH stability, pH
solubility, and ocular tolerability data, with the typical pH range for
μ
