An in vitro investigation of the suitability of press-coated tablets with hydroxypropylmethylcellulose acetate succinate (HPMCAS) and hydrophobic additives in the outer shell for colon targeting

To develop a new colon targeting formulation, which can suppress drug relea se completely during 12 h in the stomach and release the drug rapidly after a lag time of 3+/-1 h in the small intestine, the use of press-coated tabl ets with hydroxypropylmethylcellulose acetate succinate (HPMCAS) in the out er shell was investigated. The release of diltiazem hydrochloride (DIL) as a model drug contained in the core tablets in the 1st fluid (pH 1.2) was su ppressed by preparing with higher compression force, hut the lag time in th e 2nd fluid (pH 6.8) could not exceed 1.5 h. Therefore, to improve the diss olution characteristics, the effects of addition of various hydrophobic add itives to HPMCAS were examined. All of the additives examined suppressed th e release rate in the 1st fluid, and prolonged the lag time in the 2nd flui d compared to HPMCAS alone. However, although none of the additives examine d fulfilled all of the desired criteria, magnesium stearate (MgSt) and calc ium stearate (CaSt) showed interesting effects; the former suppressed drug release completely in 1st fluid, while the latter markedly prolonged the la g time in 2nd fluid. To integrate the merits of each additive, press-coated tablets with a powder mixture of HPMCAS, MgSt and CaSt in the outer shell (HMC tablets) were prepared and in vitro tests were performed. The results indicated that HMC tablets with a mixing ratio of 80% HPMCAS, 5-15% MgSt an d 15-5% CaSt in the outer shell met the desired criteria and the lag time i n 2nd fluid could also be controlled from 2 to 9 h. At a mixing ratio of 80 % HPMCAS, 10% MgSt and 10% CaSt, the dissolution profiles of DIL in 1st flu id and 2nd fluid were not remarkably affected by agitation intensity, and a ddition of bile salts, pretreatment time or anticipated higher pH except fo r pH 6.0, respectively. These results indicated the usefulness of HMC table ts with the desirable functions for colon-targeting formulations. (C) 2001 Elsevier Science B.V. All rights reserved.