Sutch Jonathan C D, Ross Alistair C, Köckenberger Walter, Bowtell Richard W, MacRae Ross J, Stevens Howard N E, Melia Colin D
Formulation Insights, School of Pharmacy, University of Nottingham, University Park, Nottingham NG7 2RD, UK.
J Control Release. 2003 Oct 30;92(3):341-7. doi: 10.1016/s0168-3659(03)00341-9.
Chronopharmaceutical capsules, ethylcellulose-coated to prevent water ingress, exhibited clearly different release characteristics when coated by organic or aqueous processes. Organic-coated capsules produced a delayed pulse release, whereas aqueous-coated capsules exhibited less delayed and more erratic release behaviour. Nuclear magnetic resonance microscopy was used to elucidate the internal mechanisms underlying this behaviour by studying the routes of internal water transport and the timescale and sequence of events leading to the pulse. Images showed that the seal between the shell and the tablet plug is a key route of water penetration in these dosage forms. There is evidence for a more efficient seal in the organic-coated capsule, and although some hydration of the contents was evident, erosion of the tablet plug is most probably the controlling factor in timed release. The premature failure of the aqueous-coated capsule appears to be a result of rapid influx of water between plug and capsule with hydration of the low substituted hydroxypropylcellulose expulsion agent. As a result of this, the tablet plug remains intact, but appears unable to be ejected. The resulting significant pressure build-up causes premature release by distortion and splitting of the capsule shell. These events may be aided by a weakening of the aqueous-coated gelatin shell by hydration from the inside, and at the mouth of the capsule where previous electron microscope studies have shown incomplete coating of the inside by the aqueous process.
采用乙基纤维素包衣以防止水分进入的时辰药理学胶囊，在通过有机或水性工艺包衣时表现出明显不同的释放特性。有机包衣胶囊产生延迟脉冲释放，而水性包衣胶囊表现出较少延迟且更不稳定的释放行为。通过研究内部水传输途径以及导致脉冲的时间尺度和事件顺序，利用核磁共振显微镜来阐明这种行为背后的内部机制。图像显示，在这些剂型中，外壳与片剂塞之间的密封是水分渗透的关键途径。有证据表明有机包衣胶囊中的密封更有效，并且尽管内容物有一些水合现象明显，但片剂塞的侵蚀很可能是控释的控制因素。水性包衣胶囊的过早失效似乎是由于水在塞子和胶囊之间快速流入，以及低取代羟丙基纤维素促渗剂水合的结果。因此，片剂塞保持完整，但似乎无法弹出。由此产生的显著压力积聚导致胶囊壳变形和裂开从而过早释放。这些事件可能因内部水合作用导致水性包衣明胶壳变弱而得到促进，并且在胶囊口处，先前的电子显微镜研究表明水性工艺对内部的包衣不完全。
