Hara Michio

The inactivation process of fibroblast interferon-β in the preparation stage and in rabbit nasal absorption of mixed and freeze-dried powder dosage forms

Abstract The present paper is concerned with a new finding with regard to the inactivation and the nasal bioavailability of IFN-β in two different powder dosage forms, i.e. mixed powder (MP) and freeze-dried powder (FP) dosage forms. The two types of preparations which contained bile salts were prepared. The IFN-β titer was determined by bioassay and enzyme immunoassay (EIA). Employing EIA, it was confirmed that the titers of sample MP and sample FP after preparation were different, while their bioavailabilities in the nasal absorption study were not significantly different. In an attempt to clarify the above result, studies of stability and rabbit nasal absorption of IFN-β were performed, additionally investigating the effects of cryoprotectants for sample FP. As a result, in the case of sample MP, rapid inactivation seemed to take place mainly on the nasal mucosal membrane during the absorption stage, while for sample FP it appears mostly during the preparation stage on freeze-drying. Additionally, the pharmacokinetic behavior of IFN-β was found to differ between both samples.