Drug release from and mechanical properties of press-coated tablets with hydroxypropylmethylcellulose acetate succinate and plasticizers in the outershell

Dissolution profiles of diltiazem hydrochloride (DIL) contained in core tab lets from press-coated (PC) tablets with hydroxypropylmethylcellulose aceta te succinate (HPMCAS) and plasticizers-adsorbent in the outer shell were in vestigated. Although, on the addition of triethyl citrate (TEC), triacetin (TA), and acetyltriethy citrate (ATEC) as plasticizers, DIL release was sup pressed 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 monoglyc eride. On the other hand, DIL in second fluid (pH 6.8) was released rapidly after a lag time ib 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 mech anical impact, tablets with HPMCAS, HPMCAS and TEC- br DBS-adsorbent (H, HT , or HD tablets, respectively) were prepared. In compressive load-strain cu rves 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 w as hard to find crushing points. These results suggested that the resistanc e of the outer shell was due to plastic deformation properties involving so me interaction between HPMCAS and TEC. (C) 2001 Elsevier Science B.V. All r ights reserved.