| GALENIC
FORMULATIONS FOR HUMAN STUDIES
Compatibility
and haemolytic potential (CD-98/6309T)
The compatibility
and haemolytic potential of IQB-9302.HCl formulated at five different concentrations,
as shown below were evaluated:
-
0.10% IQB-9302.HCl
in 0.9% saline
>
-
0.25% IQB-9302.HCl
in 0.8% saline
-
0.50% IQB-9302.HCl
in 0.8% saline
-
0.75% IQB-9302.HCl
in 0.75% saline
-
1.00% IQB-9302.HCl
in 0.75% saline
For the compatibility
test, the different concentrations of the test substance were placed in
contact with plasma and serum from human and dogs
The evaluation
of haemolytic potential of the test substance was determined by placing
whole heparinized blood from dogs and humans in contact.
Results
-
The compatibility
test in dog and human serum demonstrated that the test substance IQB-9302.HCl
formulated at the concentrations given above on mixing serum and each formulation
in the ratio 1:1 was fully compatible with no turbidity, precipitation
or formation of aggregates.
No haemolytic
activity was shown when whole heparined blood from dogs and humans was
mixed in the ratio 1:1 with the different concentrations of the test substance
IQB-9302
GLPs: This study was carried
out according to the Good Laboratory Practice regulations published by
OCDE at Centro de Investigación y Desarrollo Aplicado S.A.L. Centro
Industrial Santiga c/ Argenters 6. Santa Perpetua de Mogoda. Barcelona.
Spain.
Head Toxicology Dept: J. Zapatero.
Biologist
Study Director: M. de Luna, Biologist
QAU CIDASAL: G.
Segarra
QAU IQB: A. Soria, Biochemist
Full
Report: CD-98/6309T |
Accelerated Stability Study
The following batches of IQB-9302.HCl
were prerared for accelerated stability studies
-
0.10% IQB-9302.HCl
in 0.9% saline
-
0.25% IQB-9302.HCl
in 0.8% saline
-
0.50% IQB-9302.HCl
in 0.8% saline
-
0.75% IQB-9302.HCl
in 0.75% saline
-
1.00% IQB-9302.HCl
in 0.75% saline
Solutions were
used to fill 5 ml ampoules that were sealed and autoclaved a 121º
C for 20 minutes.
The following
analytical controls were performed (HPLC analysis)
| Solution |
0.10% |
0.25% |
0.50% |
0.75% |
1.00% |
| Fresh |
100,0% |
100.0% |
100.0% |
100.0% |
100.0% |
| After autoclaving |
99.1% |
101.2% |
99.5.0% |
99.2% |
100.4% |
| 4 months in the dark 4ºC |
98.2% |
97.6% |
100.1% |
98.4% |
100.0% |
| 4 months in the dark ambient |
98.5% |
100.1% |
98.6% |
97.2% |
100.1% |
| 4 months light ambient |
99.3% |
98.2% |
100.0% |
100.1% |
99.6% |
| 4 months in the dark 40ºC |
99.5% |
100,8% |
100.8% |
99.8% |
98.3% |
| 4 months in the dark 65ºC |
98.5% |
99.3% |
100.6% |
99.8 |
99.5 |
| 6 months in
the dark 40ºC |
98.6% |
99.1% |
99.6% |
98.6% |
99.6% |
MANUFACTURING
OF AMPOULES FOR CLINICAL TRIALS
Laboratorios INIBSA is the manufacturer
of batches of ampoules of IQB-9302. HCl, bupivacaine.HCl and placebo
needed for clinical trials. Production of ampoules is performed in sterile
clean rooms according to standard SOPs designed by Laboratorios INIBSA
to fulfil GMPs and GLPs. Figure 1
summarizes the manufacturing process.
The detailed procedure of manufacturing
for each of concentrations of IQB-9302.HCl, bupivacaine.HCl and placebo
is available (in spanish)
Ingredients used in manufacturing
IQB-9302.HCl, Bupivacaine HCl and placebo injections are analyzed
according to their corresponding monographs:
TESTING
STANDARD OF IQB-9302 HYDROCHLORIDE, BUPIVACAINE HYDROCHLORIDE AND PLACEBO
AMPOULES
A monograph
has been developed for IQB-9302 hydrochoride injection.
Bupivacaine HCl injection and placebo
(sodium chloride injection) are analized according to their corresponding
USP 23/NF 18 monographs:
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