Absorption enhancement of calcitonin in the rat intestine by carbopol-containing submicron emulsions

The absorption of salmon calcitonin (sCT) in the jejunum and the colon of the rat from submicron emulsions with (MA-SME) and without (SME) the adhesive polymer Carbopol®940 was studied in side-by-side diffusion cells and closed intestinal loops of the anesthetized rat. sCT permeated the jejunal and colonic mucosa of the rat at similar rates. However, when the sCT was introduced in MA-SME a profound enhancement (3.3-fold increase) in the diffusion rate was observed in the colon, but not in the jejunal epithelium. It was found that after intra-colonic administration, the SME formulations yielded a significant reduction in plasma Ca²⁺ levels as compared to administration of sCT in normal saline. In the case of MA-SME, the reduction was more profound (80% of Ca²⁺ of basal level at 120 min, as compared to 90% of Ca²⁺ basal level at 15 min for MA-SME and SME, respectively) and was prolonged (1.5-fold) in the case of the MA-SME. Similarly, MA-SME caused a profound increase (14.7%) in the absolute bioavailability of sCT following intra-colonic administration in the rat. Indomethacin-containing MA-SME adhered rapidly, and at similar rates, to the mucosa of everted sacks taken from the jejunum or colon of the rat. It is suggested that enhancement of sCT absorption is attributable to both adherence of the emulsion droplets to the epithelium mucosa and the protease inhibition and absorption enhancement properties of Carbopol®940.