composição liofilizada e métodos de preparação de composição seca estável do fator ix e de liofilização de formulação farmacêutica

摘要

Methods of preparing lyophilized preparations of Factor IX which preserve more than 90% of the calcium binding property of Factor IX are disclosed. Factor IX formulated with trehalose shows a superior stability profile after 12 weeks storage at 25°C/60% relative humidity (RH) and 40°C/75% RH relative to Factor IX formulated without trehalose. The data suggest that the inclusion of trehalose in the formulation could allow for temperature excursions or even long-term room temperature storage of a Factor IX lyophilized product. The formulations tested contained 10 mM histidine pH 6.8, 3% mannitol, 66 mM sodium chloride, 0.0075% Polysorbate 80, with and without 1% trehalose. Upon storage at 40°C/75% RH or 25°C/60% RH over 12 weeks the trehalose-containing formulation was comparable to product stored at 2-8°C while the formulation without trehalose was found to undergo significant aggregation and loss of activity. The two formulations demonstrated comparable stability over 26 weeks of real time storage at -20°C and 2-8°C.