The guantitative examination of gel formed in the reconstituted solutions from five lyophilized tissue plasminogen activator (t-PA) preparations was performed using a submicron particle analyzer, scanning electron microscopy and size exclusion HPLC. In two preparations containing human serum albumin (HSA), comparatively marked gel formation was observad. These gels were confirmed to be protein-containing products by X-ray emission spectrometry, suggesting that gel formation occurred by denaturation, aggregation and precipitation of t-PA and ingredients, especially HSA. The gel formation was not marked in the preparations to which was added polysorbate 80. Furthermore, the site specific change in the cake structure was observed by scanning electron microscopy, suggesting that gel is formed during the lyophilization process.
In conclusion, the optimal selection of excipient and the lyophilized condition should be desired in pharmaceutical development of the lyophilized t-PA preparation to decrease gel formation.
