Topical Tolerability of Calcitonin Nasal Preparation, its Excipients and Sodium Taurocholate Studied by SEM and Mucociliary Transport Velocity

Abstract

In addition to the active drugs, intranasal preparations contain various excipients and preservatives to stabilise the formulation and prevent the growth of contaminating microorganisms during repeated use. This study assessed the topical tolerability of 1–7 Asu eel and salmon calcitonin, the excipients ammonium glycyrrhizinate, methyl and propyl p-hydroxybenzoate and benzalkonium chloride, and sodium taurocholate, which is used in other preparations to promote absorption. The ex vivo frog palate preparation was used to measure mucociliary transport velocity (MTV) as an index of their effects. In addition, scanning electron microscopy (SEM) was used to study the morphology of the mucosal surface of the palate before and after contact with the test substances. Frog Ringer’s solution, 1–7 Asu eel and salmon calcitonin did not significantly change MTV, confirming good tolerability by ciliated epithelium. The same was true for 0.5 and 2% ammonium glycyrrhizinate and 0.01% benzalkonium chloride, while p-hydroxybenzoates produced a small though significant reduction in MTV. Sodium taurocholate, however, led to a significant reduction in MTV for the palate with and without mucus. SEM studies confirmed the results, clearly identifying the damage to epithelial ciliated cells produced by sodium taurocholate.