Freeze-drying of protein pharmaceuticalin vials with different character

Sammanfattning: Freeze-drying of protein pharmaceuticals is a procedure frequentlyused to obtain stability of the active pharmaceutical ingredientduring distribution and storage. It can be performed in pre-filledsyringes, with a lubricous coating of silicone on the inside, toenable the piston moving. The coating changes the environmentpotentially affecting the features of the freeze-dried cake sincethe wetting behavior and adhesion to the inner wall is affected.This project aimed to investigate the effect of the siliconizationof the cakes. Three different formulations were freeze-dried in nonsiliconized(NS) and siliconized vials using differentsiliconization protocols. Analysis was done using differentialscanning calorimetry (DSC), thermal gravimetric analysis (TGA),scanning electron microscopy (SEM), X-ray photoelectron spectroscopy(XPS) and an embedding method, intended to give information aboutthe cake’s shrinkage, cracking and pore-structure. The water contentin the bottom of the cakes was consistently higher than in the top,a difference decreasing over time. Increased surface hydrophobicitylead to increased shrinkage of the cake’s volume and a decrease infogging. The bottom of the protein cake in the vial siliconized witha commercial silicone emulsion consisted of pores with regularlyequal pore size and thick pore walls, a structure not seen in anyother cake. All cakes in the silicone emulsion siliconized vials hadlower water content than the cakes in the vials using the othersiliconization method. The XPS-analysis showed that the cakes in theemulsion siliconized vials contained silicon, indicating an excessof silicone when siliconizing and/or an unstable coating.