Development of Self-Emulsifying Nanoplatform as Anti-Diabetic Sulfonylurea Carrier for Oral Diabetes Therapy

This study aimed to develop a novel controlled delivery self-emulsifying nanoplatform as an anti-diabetic sulfonylurea carrier for oral diabetes therapy. G004 (1-(4-(2-(4-bromobenzenesulfonamino)ethyl)phenylsulfonyl)-3-(trans-4-methylcyclohexyl)urea) was selected here as a model drug due to its weak solubility. The formulation of the self-emulsifying drug delivery system (SEDDS) was optimized in terms of particle size and self-emulsifying time. Rat intestinal perfusion indicated that G004-SEDDS with the highest absorption in the ileum has a higher absorption than normal. The emulsion with a particle size of about 150 nm was then solidified for preparation of self-emulsifying nanoplatforms. Further study indicated that the release of G004 was significantly influenced by absorbent type, osmotic substance dosage, polyoxyethylene/povidone ratio, plasticizer varieties, plasticizer dosage and coating weight gain. The cumulative release of the optimized formulation at 12 hr was 80.9%. In vivo pharmacokinetic study showed plasma concentration-time curves took significantly longer time to reach peak plasma concentration (T _max) and showed reduced peak plasma concentration (C _max) for solidified self-emulsifying nanoplatform in comparison with solid self-emulsifying tablets. And compared with the conventional tablets, C _max of the self-emulsifying nanoplatform was decreased, while T _max was prolonged, and the relative bioavailability was 1.88 times that of conventional tablets. All the results confirmed that enhanced bioavailability and controlled release of G004 had been achieved by this novel controlled delivery self-emulsifying nanoplatform, bringing great significance and high potential to the treatment for type 2 diabetes.