Interdiction of hypoglycemia in diabetic children by multiparticulate dosage form with controlled glucose release.

Patients tend to evade the occurrence of hypoglycemic episodes by excessive carbohydrate intake. Glucose pellets with delayed release in the time of the maximum effect of insulin can not only prevent hypoglycemia but also eliminate the preventive carbohydrate intake. The pellets can be administered in a mixture with semisolid food. The cores containing glucose in combination with osmotically active agents (croscarmellose sodium, carmellose sodium, polyethylene glycol, or carboxymethyl starch) were prepared by extrusion-spheronization and coated with 15% water ethylcellulose dispersion (Surelease® B NF) in Wurster column (Medipo, Havlíckuv Brod, Czech Republic) into four coating levels (12.5, 25, 35, and 50%). Mean particle size is 0.63-0.73 for cores and 0.82-0.98 for coated pellets. Cores and coated pellets have excellent or good flow properties according to Hausner ratio and Carr index. Aspect ratio ranges from 1.78 to 2.17 for cores and from 1.73 to 2.31 for coated pellets. Dissolution was performed using pH-independent method and method with continual change of pH. The suitable pH-independent release was achieved in the samples containing carboxymethyl starch or polyethylene glycol. Glucose release is enabled by a membrane rupture caused by core swelling. It can be, therefore, assumed that the glucose release profile will not be affected by food or transit time.

[Influence of the mesh of extrusion dies on the properties of cores intended for the preparation of pellets with controlled glucose release]. / Vliv velikosti oka extruzní prepázky na vlastnosti jader urcených k príprave pelet s rízeným uvolnováním glukosy.

UNLABELLED: Diabetes mellitus and its compensation are accompanied by serious complications. One of them is hypoglycaemia, which occurs in patients treated with insulin and/or certain peroral antidiabetics. Hypoglycaemic episodes can be prevented by a dosage form with controlled release of glucose. The pellet cores of four compositions and three different sizes corresponding to the diameter of extrusion screen mesh (0.6, 0.8, and 1.0 mm) were prepared for this purpose. The cores contain 75-80% of glucose combined with one of the following osmotically or swellable active agents: croscarmellose sodium (ADS), a mixture of microcrystalline cellulose and carmellose sodium Avicel RC 591 (RC), polyethylene glycol 6000 (PEG), and carboxymethyl starch (CMS). The cores were prepared by extrusion-spheronization and are intended for subsequent coating by a semipermeable membrane based on ethylcellulose. The aim of the work was to statistically evaluate the results of the physical evaluation of the pellets which were prepared and evaluated in previously published papers. The results are processed in the form of a meta-analysis using principle component analysis. The physical characteristics of the individual pellet sizes were different among themselves. Although the same compositions and manufacturing methods were used for all the pellets sizes, the cores produced through a 0.6 and 0.8 mm mesh screens showed similar properties while the properties of cores produced through a 1.0 mm mesh screen were rather different. KEY WORDS: hypoglycemia delayed release glucose principal component analysis PCA meta-analysis of data.