LIGHT DEGRADATION OF ML7 FORMULATIONS BY OCTALIA TECHNOLOGIES CRO: CONCLUSION

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5. CONCLUSION

This report presents the data generated for the degradation study under light exposure

conducted on ML7 formulations upon Neuroptis’ request.

Based on the results, the following conclusions can be drawn:

· ML7 is significantly sensitive to light when formulated in solution. Whatever the

formulations, recoveries after light exposure are about 30-37%. This behavior was

confirmed with a ML7 aqueous solution for which a 37% recovery was also reported

after light exposure.

· Many additional peaks were reported for all the samples tested (HPMC-based batch,

HEC-based batch and ML7 aqueous solution); none of them were found pure while

ML7 peak remained pure even when an important degradation of the sample was

observed.

· The main degradation product linked to light exposure is the one having a RRT of

0.84. This peak was reported up to 17% (in % area vs ML7 standard area) in the

degraded ML7 aqueous solution and up to 28 and 30% in degraded batches E753-2

(HPMC-based batch) and E728-4 (HEC-based batch), respectively. This peak was

reported after 6-month storage at RT and 40°C but in lower levels than the

identification threshold.

· Mass balances were not fully reached for degraded samples (between 60 and 66% for

ML7 formulations and around 48% for the ML7 aqueous solution). This could be

mainly explained by the fact that some degradation peaks do not absorb in UV or are

not eluted with this HPLC method.

· This stressed degradation study under direct light exposition clearly demonstrates the

significant ML7 sensitivity to light in aqueous solution. Therefore, it is appropriate to

start considering a packaging that would adequately protect ML7 formulation from

light. This study design will then have to be reiterated to demonstrate that the

immediate packaging selected would only induce acceptable change of the product

(ICH Q1B - Photostability).

CONCLUTION: A light protection "sachet" will protect unidoses of the product after their

manufacturing