The influence of tonicity and viscosity on the intranasal absorption of salmon calcitonin in rabbits

Abstract

As with any drug delivery system, a clear understanding of the physicochemical and formulation factors is necessary for the rational design of a dosage form. Formulation factors need to be carefully assessed to identify those which may influence pharmacological or physiological response and thus assure optimum therapeutic activity. On the basis of physicochemical and biopharmaceutical studies a nasal peptide formulation when administered with an appropriate delivery device may be designed to provide optimal nasal activity. In the present study an attempt was made to investigate the effect of tonicity and viscosity on the intranasal absorption of salmon calcitonin (sCT). Formulations were designed as nasal sprays with viscosity at 1 and 76 cps, using 0% w/w and 1% w/w methylcellulose as the viscosity enhancing agent; and with a tonicity of 100, 300 or 600 mOsms, using sodium chloride as the tonicity adjusting agent. The low viscosity formulations were delivered using a metered nasal spray pump and the high viscosity formulations were administered using a prototype device, the nasal micron spray pump (NMSP), to facilitate a uniform distribution of the spray into the nasal cavity. Serum levels of sCT were determined in healthy male New Zealand rabbits after intranasal administration of 2000 I.U. of sCT in 200 μl. The pharmacodynamic effect of salmon calcitonin of lowering blood calcium levels was measured using a visible spectrophotometric technique. Deviation from isotonicity increased the bioavailability by 4–5 times. Variation in the viscosity did not influence the bioavailability of salmon calcitonin. Response surface methodology and the canonical analysis parameters were applied to predict the optimum formulations.