Gastrointestinal absorption enhancement of insulin by administration of enteric microspheres and SNAC to rats.

The preparation and characteristics of insulin enteric microspheres (EMS) were studied and the gastrointestinal absorption enhancement of insulin by co-administering EMS with sodium N-(8-[2-hydroxybenzoyl] amino) caprylate (SNAC) was determined. The w/o/w and o(1)/o(2) emulsion solvent evaporation methods were used to prepare insulin-hydroxypropyl methylcellulose phthalate (HPMCP) EMS. High-performance liquid chormatography determined the drug loading, entrapment efficiency, stability to pepsin, and drug dissolution rate in hydrochloric acid solution (pH 1.2) and phosphate buffer solution (pH 6.8). The hypoglycaemic effect was studied by orally administrating the insulin EMS and SNAC to rats. The particle size of EMS (o(1)/o(2)) and EMS (w/o/w) was about 500 and 30 micro m respectively, and drug loading was 7 and 3% respectively. After being incubated with 18 micro g/mL pepsin solution (pH 1) at 37 degrees C, only 20% of insulin in EMS (o(1)/o(2)) was digested within 4 h, while 60% of the insulin in EMS (w/o/w) was digested within 1 h. In hydrochloric acid solution (pH 1.2), EMS (o(1)/o(2)) had less drug dissolution than EMS (w/o/w). In phosphate buffer solution (pH 6.8), the entire drug release time of EMS (o(1)/o(2)) and EMS (w/o/w) was 75 and 10 min, respectively. After orally administering with SNAC, EMS (o(1)/o(2)) could decrease the blood glucose level of rats remarkably and maintain the hypoglycaemic effect for 4 h, while EMS (w/o/w) had just a weakly hypoglycaemic effect. The results showed that the characteristics-optimized EMS, i.e. EMS (o(1)/o(2)) incorporating SNAC, could enhance insulin absorption significantly in the gastrointestional tract by taking advantage of both protection from enzyme degradation and improvement of drug permeability.