Drug release from and mechanical properties of press-coated tablets with hydroxypropylmethylcellulose acetate succinate and plasticizers in the outer shell.
Dissolution profiles of diltiazem hydrochloride (DIL) contained in core tablets from press-coated (PC) tablets with hydroxypropylmethylcellulose acetate succinate (HPMCAS) and plasticizers-adsorbent in the outer shell were investigated. Although, on the addition of triethyl citrate (TEC), triacetin (TA), and acetyltriethy citrate (ATEC) as plasticizers, DIL release was suppressed completely in first fluid (pH 1.2) for 10 h, it was not suppressed in HPMCAS on the addition of dibutyl sebacate (DBS) and acetylated monoglyceride. On the other hand, DIL in second fluid (pH 6.8) was released rapidly after a lag time in all the PC tablets. Water-soluble plasticizers such as TEC, TA, and ATEC showed greater compatibility to HPMCAS, and the results were consistent with suppression of DIL release in first fluid. Furthermore, as to PC tablets with HPMCAS and TEC-adsorbent, the DIL release in second fluid did not change after pretreatment in first fluid by the paddle-beads methods. To evaluate the resistance of the outer shell against such a mechanical impact, tablets with HPMCAS, HPMCAS and TEC- or DBS-adsorbent (H, HT, or HD tablets, respectively) were prepared. In compressive load-strain curves after immersion in first fluid, wet crushing strength was lower in the order of HT > H > HD tablets. Also, the curves of HT tablets at 3 and 21 h after immersion were quite different from those of other tablets, and it was hard to find crushing points. These results suggested that the resistance of the outer shell was due to plastic deformation properties involving some interaction between HPMCAS and TEC.
Fukui
E
E
Product & Technology Development Laboratory, Tanabe Seiyaku Co., Ltd., 16-89 Kashima-3-chome, Yodogawa-ku, 532-0085, Osaka, Japan. fukui@tanabe.co.jp
Miyamura
N
N
Yoneyama
T
T
Kobayashi
M
M
D002317:Cardiovascular Agents / Q000737:chemistry*; D019245:Compressive Strength; D004110:Diltiazem / Q000737:chemistry*; D019563:Mechanics; D008747:Methylcellulose / Q000031:analogs & derivatives / Q000737:chemistry*; D010968:Plasticizers / Q000737:chemistry*; D012995:Solubility; D013608:Tablets, Enteric-Coated
D002317:Cardiovascular Agents; D010968:Plasticizers; D013608:Tablets, Enteric-Coated; C048331:hydroxypropylmethylcellulose acetate succinate; D008747:Methylcellulose; D004110:Diltiazem