Studies on applicability of press-coated tablets using hydroxypropylcellulose (HPC) in the outer shell for timed-release preparations.
Press-coated tablets, containing diltiazem hydrochloride (DIL) in the core tablet and coated with hydroxypropylcellulose (HPC) as the outer shell, were examined for applicability as timed-release tablets with a predetermined lag time and subsequent rapid drug release phase. Various types of press-coated tablets were prepared using a rotary tabletting machine and their DIL dissolution behavior was evaluated by the JP paddle method. The results indicated that tablets with the timed-release function could be prepared, and that the lag times were prolonged as the viscosity of HPC and the amount of the outer shell were increased. The lag times could be controlled widely by the above method, however, the compression load had little effect. Two different kinds of timed-release press-coated tablets that showed lag times of 3 and 6 h in the in vitro test (denoted PCT(L3) and PCT(L6), respectively) were administered to beagle dogs. DIL was first detected in the plasma more than 3 h after administration, and both tablets showed timed-release. The lag times showed a good agreement between the in vivo and in vitro tests in PCT(L3). However, the in vivo lag times were about 4 h in PCT(L6) and were much shorter than the in vitro lag time. The dissolution test was performed at different paddle rotation speeds, and good agreement was obtained between the in vivo and in vitro lag times at 150 rpm. This suggested that the effects of gastrointestinal peristalsis and contraction should also be taken into consideration for the further development of drug delivery systems.
Fukui
E
E
Product and Technology Development Laboratory, Tanabe Seiyaku Co., Ltd. 16-89 Kashima 3-chome, Yodogawaku, 532-8505, Osaka, Japan. fukui@tanabe.co.jp
Uemura
K
K
Kobayashi
M
M
D000818:Animals; D002482:Cellulose / Q000008:administration & dosage / Q000031:analogs & derivatives*; D004110:Diltiazem / Q000008:administration & dosage / Q000493:pharmacokinetics; D004285:Dogs; D016503:Drug Delivery Systems; D006863:Hydrogen-Ion Concentration; D008297:Male; D011312:Pressure; D012995:Solubility; D013607:Tablets; D014783:Viscosity
D013607:Tablets; D002482:Cellulose; C008079:hydroxypropylcellulose; D004110:Diltiazem