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.

Coated pellets with delayed-release glucose for prevention of hypoglycemic episodes

“…Considering the dissolution profiles of the CMS sample, the lag time was prolonged from 60 min (25 % coating) to 360 min (50 % coating), with a sufficient amount of released glucose. It can be assumed that these lag times would also be reached in vivo, since glucose release from the samples containing carboxymethyl starch is unaffected by the change of pH (22). This suggests that the pellet composition containing carboxymethyl starch is most suitable for the intention of this work and for future use.…”

Clinical assessment of the lag‐time and tmax of pellets with controlled release of glucose: in vitro/in vivo comparison using 13C–breath test

“…The pellet morphology and coating thickness is documented in the SEM image (Figure ). Since the pellet size and morphology considerably affect the lag time, the pellet size and coating thickness were chosen to reach a lag time suitable for diabetology practice according to previously published experiments (Franc et al, , ; Sabadková, Franc, Muselík, & Neumann, ). The pellets containing 13 C–glucose are physically and pharmaceutically identical to those without the 13 C–label as they are prepared for personalized food.…”

“…The pellets were prepared according to previously described methodology (Franc et al, ). The current core composition corresponded to the original sample of carboxymethyl starch with added 13 C–glucose.…”

“…The dissolution conditions were determined in previous experiments. It was found that the lag time was unaffected by the rotation speed of the dissolution apparatus and the pH of the dissolution media (Franc et al, , ). Furthermore, it was verified that the type of dissolution apparatus (basket vs. paddle apparatus) did not influence the lag time either (unpublished results).…”

“…This simple calculation of the clinical lag time can be used due to the pellet composition and characteristics. Since the lag time is unaffected by changes in pH or mechanical stress, it remains unchanged during the gastrointestinal passage (Franc et al, , ).…”