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 time d-release press-coated tablets (ETP tablets) were developed by coating ente ric polymer on timed-release press-coated tablets composed of an outer shel l of hydroxypropylcellulose and core tablet containing diltiazem hydrochlor ide (DIL) as a model drug. The results of the in vitro dissolution tests in JP Ist fluid (pH 1.2) and JP 2nd fluid (pH 6.8) indicated that these table ts showed both acid resistance and timed-release. To clarify whether ETP ta blets could have been of use in the gastrointestinal tract, ETP tablets wit h a layer of phenylpropanolamine hydrochloride (PPA) (a marker of gastric e mptying) between the enteric coating layer and outer shell were prepared, a nd were administered to beagle dogs. The gastric emptying time and lag time after gastric emptying were evaluated by determining the time:; at which P FA and DIL first appeared in the plasma (TFA(PPA) and TFA(DIL), respectivel y). 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 stoma ch 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 vi tro dissolution test in JP 2nd fluid. Also, the results seemed to be in acc ordance with the time at which the tablets reached the colon after gastric emptying. Therefore, ETP tablets seemed to be an effective tool for oral si te-specific delivery including targeting of the colon. (C) 2000 Elsevier Sc ience B.V. All rights reserved.