WET SPHERICAL AGGLOMERATION OF PROTEINS AS A NEW METHOD TO PREPARE PARENTERAL FAST SOLUBLE DOSAGE FORMS

Using a wet spherical agglomeration technique it was possible to form agglomerates from a powder containing proteins by suspending it in an organic liquid and adding a small amount of an aqueous liquid with a pH that guarantees good stability of the protein. Regarding the size distribution of the agglomerates an optimal amount of aqueous bridging liquid could be defined. Using bovine serum albumin (BSA) as a low-cost model protein, the influence of various parameters on the agglomeration process was evaluated. The disintegration time could be influenced by the type and the amount of added excipient. The optimal amount of bridging liquid needed could be predicted at each protein/excipient ratio, the experimental results showing good agreement with the predicted values. The resulting agglomerates were nearly spherical and the yield in the range between 250 and 1000 mu m was over 80% (w/w). Also, it was possible to agglomerate recombinant bovine alpha(I)(1)-interferon as a model for a bioactive protein to spherical agglomerates with a good yield. The agglomeration behaviour of interferon was similar to that of BSA. It could be shown that the procedure of agglomeration using n-hexane has no influence on the biological activity of this protein.