Use of enzymatic activity for design of orally administered enteric dosing forms.
Liquid and semi-solid enteric dosage forms were prepared by entrapping drug with an appropriate partition coefficient in a lipid base vehicle which would then be released by the action of intestinal enzymes. Lipid ester derivatives such as glyceryl monocaprylate and polysorbate 80 were used as vehicles. These vehicles readily dissolved the poorly water-soluble compounds used in the study, itazigrel, indomethacin and the dye, sudan II, and were digested by lipase and esterase, releasing the test drugs with time profiles similar to those observed in dissolution studies. The vehicles released little or only a small amount of the drugs into aqueous medium in the absence of an appropriate enzyme. The enzyme-sensitive enteric vehicles when containing sudan II did not release the dye in the stomach of rats after oral administration, but released significant amounts of the dye in the small intestine.
Nishihata
T
T
Upjohn Tsukuba Research Laboratories, Upjohn Pharmaceuticals Limited, Ibaraki, Japan.
Yamamoto
K
K
Ishizaka
M
M
D000818:Animals; D001391:Azo Compounds / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D015195:Drug Design; D004798:Enzymes / Q000378:metabolism*; D004950:Esterases / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007213:Indomethacin / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics; D008049:Lipase / Q000378:metabolism; D008297:Male; D014677:Pharmaceutical Vehicles; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013608:Tablets, Enteric-Coated; D013844:Thiazoles / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics
D001391:Azo Compounds; D004798:Enzymes; D014677:Pharmaceutical Vehicles; D013608:Tablets, Enteric-Coated; D013844:Thiazoles; C033003:sudan red; D004950:Esterases; D008049:Lipase; C035025:itazigrel; D007213:Indomethacin