Nateglinide controlled release tablet containing compressionable enteric coated granules.

We designed a single unit type controlled release tablet containing nateglinide to decrease both postprandial blood glucose level (PBG) and fasting blood glucose level (FBG) in normal beagle dogs. The tablet contains 60 mg of nateglinide in an immediate release portion, and 90 mg of nateglinide in a controlled release portion. Compressionable enteric coated granules were selected as the controlled release portion to primarily decrease FBG, and they were prepared by an aqueous coating with Eudragit. Three types of nateglinide controlled release tablets were obtained, and their weights were 418.1-425.1 mg/tablet containing the above compressionable enteric coated granules. Even after tableting, the dissolution behavior of enteric coated granules was maintained approximately. In vivo single oral administration studies using normal male beagle dogs demonstrated that these tablets were able to decrease both PBG and FBG. The relative bioavailability values of the obtained tablets containing enteric coated granules having a dissolution pH of 6.0 and 6.8 were estimated at about 57.2 and 60.8% respectively against nateglinide immediate release tablets. In an in vivo repeated administration study with the tablets containing enteric coated granules having a dissolution pH of 6.8 (an interval: 8 h), decreases in both PBG and FBG were observed continuously twice. On the basis of the above results, it is expected to enable control of both PBG and FBG for moderate and severe diabetes patients with a controlled release formulation containing a short-acting type oral blood glucose regulator, not only nateglinide but also meglitinides (repaglinide, mitiglinide, etc.).