Preparation of enteric coated timed-release press-coated tablets and evaluation of their function by in vitro and in vivo tests for colon targeting.
As a new oral drug delivery system for colon targeting, enteric coated timed-release press-coated tablets (ETP tablets) were developed by coating enteric polymer on timed-release press-coated tablets composed of an outer shell of hydroxypropylcellulose and core tablet containing diltiazem hydrochloride (DIL) as a model drug. The results of the in vitro dissolution tests in JP 1st fluid (pH 1.2) and JP 2nd fluid (pH 6.8) indicated that these tablets showed both acid resistance and timed-release. To clarify whether ETP tablets could have been of use in the gastrointestinal tract, ETP tablets with a layer of phenylpropanolamine hydrochloride (PPA) (a marker of gastric emptying) between the enteric coating layer and outer shell were prepared, and were administered to beagle dogs. The gastric emptying time and lag time after gastric emptying were evaluated by determining the times at which PPA and DIL first appeared in the plasma (TFA(PPA) and TFA(DIL), respectively). TFA(PPA) and TFA(DIL) were about 4 and 7 h, respectively. This value of TFA(PPA) indicated that ETP tablets displayed acid resistance in the stomach as well as in JP Ist fluid. Subtraction of TFA(PPA) from TFA(DIL) gave a value of about 3 h which agreed well with the lag time determined by in vitro dissolution test in JP 2nd fluid. Also, the results seemed to be in accordance with the time at which the tablets reached the colon after gastric emptying. Therefore, ETP tablets seemed to be an effective tool for oral site-specific delivery including targeting of the colon.
Fukui
E
E
Product & Technology Developnent Laboratory, Tanabe Seiyaku Co. Ltd, Osaka, Japan. fukui@tanabe.co.jp
Miyamura
N
N
Uemura
K
K
Kobayashi
M
M
D000284:Administration, Oral; D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage / Q000097:blood* / Q000737:chemistry; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000097:blood* / Q000737:chemistry; D002482:Cellulose / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D003106:Colon / Q000378:metabolism; D003692:Delayed-Action Preparations; D004110:Diltiazem / Q000008:administration & dosage / Q000097:blood* / Q000737:chemistry; D004285:Dogs; D016503:Drug Delivery Systems / Q000379:methods*; D005746:Gastric Emptying / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D008297:Male; D010665:Phenylpropanolamine / Q000008:administration & dosage / Q000097:blood* / Q000737:chemistry; D011108:Polymers / Q000008:administration & dosage / Q000493:pharmacokinetics; D013607:Tablets
D000316:Adrenergic alpha-Agonists; D000959:Antihypertensive Agents; D003692:Delayed-Action Preparations; D011108:Polymers; D013607:Tablets; D010665:Phenylpropanolamine; D002482:Cellulose; C008079:hydroxypropylcellulose; D004110:Diltiazem