Studies On Insulin Self-Microemulsifying Drug Delivery Systems For Intranasal Administration

SMEDDS (Self-Microemulsifying Drug Delivery Systems) as a novel DDS were currently of interest to the pharmaceutical scientists. These systems were stable, could make drugs absorbed fast and completely, and could increase curative effect, decrease side-effect of drugs. Self-microemulsifying and biological conglutinate techniques were combined to apply in the powder inhalant for respiratory tract administration in the research. Through drawing (pseudo) ternary phase diagram to screen the best formula which comprised water, oik surfactant, cosurfactant. At first, insulin was prepared to concentrated microemulsions, and then mixed with chitosan. The mixture became powder , which had biological conglutination via freeze-drying. When the system was administrated into nasal cavities, powder were self- microemulsified to microemulsions in the wet environment. Nanometer particles were easy to help drug to permeate the nasal mucosa. Drugs entered into body and exerted curative effect through abundant capillary and lymphatic vessels in the nasal mucosa. On the one hand, the bioavailability of insulin was increased obviously. On the other hand, the absorption and availability of drug were more completely, because when the mixture containing drug expanded after sopping up which could be held in the nasal cavities for a long time.The methods of toad palate model in vitro and in situ were used to investigate the toxicity of nasal capillary after single administration. The nasal membrane of SD rats as experimental materials, the method of scanning electron microscope was used to investigate the toxicity of nasal membrane after multiple administrations. The results of experiments showed that insulin and excipient was used in the formulation that was screened finally were nontoxic to nasal capillary of rats. This preparation was safe to the structure of nasal mucosa organization and configuration of mucosa surface of rats after continuous seven days (3 times/day) administrations.Normal rats ^ diabetic rats ^ normal rabbits -. normal dogs as experimental models were used to do researches for pharmacodynamic studies of insulin microemulsions and SMEDDS. Insulin SMEDDS were proved that they could be self-microemulsified to nanometer particles in the aqueous environment of rabbits' nasal cavities basically. The nanometer particles could help drugs to contact with nasal membrane and enter into systemic circulation rapidly and exert curative effect. The relative pharmacological bioavailability of l.OIU/kg insulin microemulsions given to normal rats' nasal specifically was about 25.46% comparing with insulin aqueous solution for peritoneal injection; the relative pharmacological bioavailability of 1.0IU/kg insulin microemulsions given to diabetic rats' nasal specifically was about 31.71% comparing with insulin aqueous solution for peritoneal injection, it was slightly more than normal rats'. Normal beagle dogs as experimental models, the relative pharmacological bioavailability was about 20.23%, the relative bioavailability was 12.0%. The primary pharmacokinetic studies of normal dogs showed that the elevation of plasma insulin concentration was in accord with decline trend of blood glucose level. This proved the possibility of further clinical studies on insulin microemulsions via nasal route.The results of experiments indicated this insulin SMEDDS was safe and effective.