IN-VITRO TOLERABILITY OF HUMAN NASAL-MUCOSA - HISTOPATHOLOGICAL AND SCANNING ELECTRON-MICROSCOPIC EVALUATION OF NASAL FORMS CONTAINING SANDOSTATIN(R)

An in vitro human nasal model was developed as a tool to study the loc al tolerabiliity of nasal powder forms using excised nasal mucosa in a diffusion chamber. The suitability of this model was tested using San dostatin(R) (SMS) an octapeptide analog of somatostatin, as a referenc e drug enhanced by Avicel(R) (microcrystalline cellulose) or lactose ( 100 mesh). The standard nasal spray vehicle was taken as a harmless co ntrol and 1% chenodeoxycholate (CDC) as a harmful control in terms of local tolerability. The extent of peptide permeation was determined by measuring SMS concentration in the receiving chamber. The labeling of SMS was detected by immunoperoxidase staining on cross sections. The local tolerability for all tested forms was assessed by histopathologi cal examination and scanning electron microscopy. The apparent permeat ion coefficient allowed us to rank the absorption of the tested drug f orms as Avicel > spray=lactose > 1%CDC. For all formulations, SMS was detected in the epithelium. No changes of the nasal mucosa could be ob served with Avicel, lactose or nasal spray vehicle in the presence or absence of SMS. 1%CDC with or without drug showed an immediate destruc tion of the nasal epithelium. The validation of this in vitro model us ing human nasal mucosa will be further discussed as a tool for assessi ng the local tolerability of intranasally applied test substances.