Dissolution study under high mechanical-force conditions. The influence of mechanical force at different rotation speeds on the APAP release rate was investigated. Figure 4 shows
dissolution profiles of APAP from HS or HPMC matrix tablets (HS or HPMC/APAP /MCC = 60%/10%/30%). The experiments were performed
using a USP Type 1 apparatus at a rotation speed of 100 rpm in a JP-2 buffer containing α-amylase in a 5-µg/L concentration.
Under these conditions, the release rates of APAP from the HS tablet and the HPMC tablet were almost identical, but the drug-release
mechanisms were different. HS matrix tablets were hardly eroded, whereas HPMC matrix tablets gradually became smaller by erosion.
Figure 5 shows the dissolution profiles of APAP of HS or HPMC matrix tablets (HS or HPMC/APAP/MCC = 60%/10%/30%). The experiments
were performed using a USP Type 2 apparatus at rotation speeds of 50 or 200 rpm in a JP-2 buffer containing α-amylase in a
5-µg/L concentration. Under these conditions, the drug-release profiles of HPMC were remarkably accelerated by increasing
rotation speed. On the other hand, those of HS matrix tablets were hardly affected by rotation speed. The difference of 85%
APAP release time between 50 and 200 rpm of HPMC and HS were respectively 3.4 h and 0.9 h.
Figure 6 is a schematic description of gelling and drug release of HS and HPMC matrix tablets in dissolution tests. The HS
matrix tablets could retain the gel matrix structure with resistance to erosion because the swollen particles of HS did not
entirely dissolve and maintain the gel-matrix structure. On the other hand, the HPMC gel layer of the tablet surface was gradually
eroded because HPMC particles dissolved completely and could not maintain gel structure. Therefore, the rate of dissolution
was accelerated by rapid paddle rotation.
Zero-order release. The effects of PEG on drug-release profiles were investigated to make the formulation of zero-order release matrix tablets.
HS or HPMC matrix tablets containing various model drugs (ETZ, APAP, and SSA) with or without PEG, were used in this study.
Figure 7 shows the dissolution profiles of model drugs from HS and HPMC matrix tablets. Table II shows the formulations of
the tablets. The experiments were performed using a USP Type 1 apparatus at a rotation speed of 100 rpm in a JP-2 buffer containing
α-amylase in a 5-µg/L concentration. For HS matrix tablets, HS could control the drug-release profiles from first-order to
zero-order depending on PEG concentration, regardless of drug solubility. In contrast, HPMC tablets could not provide zero-order
release, especially in the case of water-soluble drugs.
Kazuhiro Obae is a chief engineer in the Ceolus Research and Development Department at Asahi Kasei Chemicals Corporation, 1-105 Kanda Jinbocho, Chiyoda-ku, Tokyo 101-8101 Japan.
Articles by Kazuhiro Obae
Yoshihito Yaginuma is a general manager, all in the Ceolus Research and Development Department at Asahi Kasei Chemicals Corporation.
Articles by Yoshihito Yaginuma
FDASIA was signed into law two years ago. Where has the most progress been made in implementation?