DELAYED-RELEASE TABLETS USING HYDROXYETHYLCELLULOSE AS A GEL-FORMING MATRIX

Delayed-release tablets containing diltiazem hydrochloride (DIL) were prepared by using CM-type hydroxyethylcellulose (HEC) of three viscosi ty grades. The tablets consisted of a core containing 30 mg of DIL and an outer shell formed by compressing HEC. DIL in the core was rapidly released from the tablets after a lag time of several hours in all ca ses. The lag time to the start of release of DIL was more prolonged wi th an increase in viscosity of CM-type HEC. The rate of water-uptake w as greater in the CM-L4 type HEC tablet of a low viscosity grade (14 c ps) than those in CM-LS and CM-L2 type HEC (27 and 95 cps, respectivel y) tablets. There was little difference in lag time to the start of re lease of DIL from CM-type HEC tablets between JP XII Ist (pH 1.2) and 2nd (pH 6.8) fluids. A human volunteer study was performed using the d elayed-release tablets prepared with CM-type HEC of two or three visco sity grades. The t(max) and MRT values of CM-type HEC tablets were sig nificantly increased with an increase in viscosity of HEC and showed o nly small variations between subjects, respectively. On the other hand , although the AUC values were almost the same, the C-max values decre ased with prolongation of lag time. The lag time in vivo for appearanc e of DIL in the blood corresponded well to the lag time in vitro for d rug release, but tended to be shortened as compared with the lag time in vitro. These results indicate that the lag time can be optionally c ontrolled by selecting HEC with a proper viscosity and/or by changing the amount of HEC forming the outer shell. This delayed-release tablet using HEC will be useful for control of time-related symptoms which n eed time-controlled or site-specific delivery in the gastrointestinal tract.