Enteric-coated cholylsarcosine microgranules for the treatment of short bowel syndrome.

Cholylsarcosine (CS) is a semisynthetic bile salt that may be useful in bile salt replacement therapy of short bowel syndrome (SBS). In SBS the bile salt pool becomes depleted, disturbing the uptake of dietary lipids and resulting in weight loss. Previous studies showed that CS in a simple capsule formulation of 1.5-12 g day(-1) can increase the uptake of lipids but often results in gastric irritation. In this work a microgranule dosage form was developed to protect the gastric mucosa while facilitating rapid generation of CS levels in the duodenum. CS microgranules were produced by wet granulation and coated with Eudragit L30D-55 in a fluidized-bed coater. The in-vitro dissolution rate of CS from the microgranules was investigated with USP apparatus under fasted- and fed-state conditions. CS release was delayed under simulated gastric conditions (pH 1.2 and 4.5) but was very fast at higher pH values (5.5, 5.8 and 6.5) more typical of the duodenum. In a pilot clinical trial, four patients received 4 g CS with meals (1.5 g with lunch, 2.5 g with dinner) for 1 week. The parameters investigated were fat absorption coefficient (FAC%), serum beta-carotene level and faecal weight. Although study numbers were too small to achieve statistical significance, the serum beta-carotene level and FAC% increased in the three patients who completed the trial. As expected, the fecal weight did not change. The results indicate that the CS microgranules are promising for the treatment of the intraluminal bile salt deficiency in patients with SBS.