Site-specific drug delivery to the middle region of the small intestine by application of enteric coating with hypromellose acetate succinate (HPMCAS).
Enteric coatings that deliver drugs to specific regions of the small intestine were examined. Hypromellose acetate succinate (HPMCAS) with different values of succinoyl group contents was used. Decreasing the succinoyl group content resulted in an increase in the pH at which HPMCAS started to dissolve. Drug-containing granules with or without enteric coating were prepared and their in vitro dissolution in a simulated intestinal fluid of pH 6.8 was examined. Granules coated with HPMCAS having the succinoyl group content of 6.2% showed a lag time of about 30 min, although drug release from granules without coating was completed within 20 min. The time lag and dissolution rate were extended and reduced, respectively, as the succinoyl group content was decreased. Rat experiments indicated that enteric-coated granules disintegrated and the bulk of the drugs was immediately released when the granules reached a specific site of the small intestine where the pH corresponded to the pH at which the enteric coating agent started to dissolve. Similar results were observed in monkey experiments. It was suggested that HPMCAS with the succinoyl group content of about 5% was suitable as an enteric coating agent for delivering drugs to the middle-to-lower region of the small intestine.
Tanno
Fumié K
FK
Specialty Chemicals Research Center, Shin-Etsu Chemical Co, Ltd, 28-1, Nishifukushima, Joetsu, Niigata, Japan.
Sakuma
Shinji
S
Masaoka
Yoshie
Y
Kataoka
Makoto
M
Kozaki
Toshio
T
Kamaguchi
Ryosei
R
Ikeda
Yutaka
Y
Kokubo
Hiroyasu
H
Yamashita
Shinji
S
D000818:Animals; D004337:Drug Carriers / Q000737:chemistry / Q000493:pharmacokinetics; D005079:Excipients; D006863:Hydrogen-Ion Concentration; D007421:Intestine, Small / Q000378:metabolism*; D008253:Macaca mulatta; D008297:Male; D008747:Methylcellulose / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D012460:Sulfasalazine / Q000008:administration & dosage / Q000493:pharmacokinetics; D013608:Tablets, Enteric-Coated; D013806:Theophylline / Q000008:administration & dosage / Q000493:pharmacokinetics; D014018:Tissue Distribution