Thermoreversible Gel Formulation for the Intranasal Delivery of Salmon Calcitonin and Comparison Studies of In Vivo Bioavailability.

Abstract

Objectives: We developed original thermoreversible (sol-gel) formulations of salmon calcitonin (sCT) for nasal applications. The sol-gel has been compared with commercial intranasal sprays in vitro and in vivo studies. The aim of studying sol-gel form is to arrange the viscosity of formulations for a reversible adequate fluidity at different temperatures. This situation may facilitate the use of drugs as sprays and increase the bioadhesive ability to mucosa.

Materials and methods: Characterization of optimum formulations was studied. Validated analytical assays determined the number of sCT. An approximately equal number of commercial and sol-gel dosages were sprayed into the nostrils of the rabbits. Blood samples were collected from the ear veins of rabbits and determined by enzyme immunoassay plates. These plates were evaluated by Thermo Labsystem Multiscan Spectrum at 450 nm. Thanks to Winnonlin 5.2, pharmacokinetic data were evaluated by a non-compartmental method.

Results: The absolute bioavailability of the formulation at pH 4 and the commercial product (CP) was compared by evaluating the primary pharmacokinetic data area under the curve 0→t_last. The absolute bioavailability of the commercial intranasal spray was measured 1.88 based on maximum concentration (C_max) assessment. C_max of the sol-gel formulation pH 4 was calculated as 0.99 and the relative bioavailability was obtained 53.3%.

Conclusion: In vivo pharmacokinetic data of sol-gel formulation with pH 3 showed significantly higher volume of distribution parameter than the CP (111167>35408). It is thought that the formulation adhered to the nasal mucosa releases sCT slowly and less.