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

Abstract

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, Havlíčkův 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.