In this study the possibility to deliver the
acid-sensitive
enzyme alkaline phosphatase (AP) from calf intestine (CIAP) to the intestinal system by
oral administration was investigated.
Tablets were prepared and in vitro evaluated. Final proof of concept studies were performed in rats. This
acid labile
enzyme is potentially useful in the treatment of
sepsis, a serious condition during which
endotoxins can migrate into the blood stream. The CIAP was freeze-dried with
inulin and subsequently compacted into round biconvex
tablets with a diameter of 4mm and a weight of 25-30 mg per
tablet. The
tablets were coated with an enteric coating in order to ensure their survival in the stomach. In vitro evaluation of
tablets containing
alkaline phosphatase from bovine intestine (
BIAP) was the first step in the development. It was found that
tablets without enteric coating dissolved rapidly in 0.10 M HCl with total loss of enzymatic activity of the
alkaline phosphatase.
Tablets that were coated were stable for at least 2 h in 0.10 M HCl, but dissolved rapidly when the pH was increased to 6.8. Furthermore, it was shown that the enzymatic activity of the released
BIAP was fully preserved. The in vivo test clearly showed that the
oral administration of
enteric coated tablets resulted in the release of enzymatically active CIAP in the intestinal lumen of rats. The location of the enhanced enzymatic activity of AP in the intestines varied with the time that had passed between the administration of the
tablets and the sacrificing of the rats. Also, the level of enzymatic activity increased with an increasing number of
tablets that were administered.