GEA-NUS Pharmaceutical Processing Research Laboratory, Department of Pharmacy, National University of Singapore, 18 Science Drive 4, Singapore 117543, Singapore.
Engineering Science Programme, Faculty of Engineering, National University of Singapore, 9 Engineering Drive 1, Singapore 117575, Singapore.
Eur J Pharm Biopharm. 2020 Jan;146:93-100. doi: 10.1016/j.ejpb.2019.11.006. Epub 2019 Nov 28.
Damage to the drug diffusion coat barrier of controlled release pellets by the compaction force when preparing multiple-unit pellet system tablets is a major concern. Previous studies have shown that pellets located at the tablet axial and radial peripheral surfaces were more susceptible to damage when compacted due to the considerable shear encountered at these locations. Hence, this study was designed to assess with precision the impact of pellet spatial position in the compact on the extent of coat damage by the compaction force via a single pellet in minitablet (SPIM) system. Microcrystalline cellulose (MCC) pellet cores were consecutively coated with a drug layer followed by a sustained release layer. Chlorpheniramine maleate was the model drug used. Using a compaction simulator, the coated pellets were compacted singly into 3 mm diameter SPIMs with MCC as the filler. SPIMs with individual pellets placed in seven positions were prepared. The uncompacted and compacted coated pellets, as SPIMs, were subjected to drug release testing. The dissolution results showed that pellets placed at the top-radial position were the most susceptible to coat damage by the compaction force, while pellets positioned within the minitablet at the middle and upper quadrant positions showed the least damage. The SPIM system was found to be effective at defining the extent of coat damage to the pellet spatial position in the compact. This study confirmed that coated pellets located at the periphery were more susceptible to damage by compaction, with pellets located at the top-radial position showing the greatest extent of coat damage. However, if the pellet was completely encrusted by the cushioning filler, coat damage could be mitigated. Further investigations were directed at how the extent of coat damage impacted drug release. Interestingly, small punctures were found to be most detrimental to drug release whilst coats with large surface cuts did not completely fail. A damaged pellet coat has some self-sealing ability and failure is not total. Thus, this study provides a deeper understanding of the consequence of coat damage to drug release when sustained release coated pellets are breached.
在制备多单位微丸系统片剂时，压缩力对控释微丸扩散包衣层的损害是一个主要关注点。先前的研究表明，由于在这些位置会遇到相当大的剪切力，因此位于片剂轴向和径向周边表面的微丸在压缩时更容易受到损坏。因此，本研究旨在通过微丸中单粒压片（SPIM）系统精确评估微丸在压缩时的空间位置对包衣层因压缩力而损坏程度的影响。微晶纤维素（MCC）微丸核依次包上药物层和持续释放层。马来酸氯苯那敏是模型药物。使用压缩模拟器，将涂覆的微丸单独压缩成 3 毫米直径的 SPIM，MCC 作为填充剂。制备了将单个微丸置于七个位置的 SPIM。未压缩和压缩的包衣微丸作为 SPIM 进行药物释放测试。结果表明，位于顶部-放射状位置的微丸最容易受到压缩力对包衣层的损坏，而位于中间和上部象限位置的微丸受到的损坏最小。SPIM 系统有效地定义了包衣微丸在压缩中的空间位置的损坏程度。这项研究证实，位于周边的包衣微丸更容易受到压缩的损坏，位于顶部-放射状位置的微丸显示出最大程度的包衣损坏。然而，如果微丸完全被缓冲填充剂覆盖，包衣损坏可以减轻。进一步的研究集中在包衣损坏程度如何影响药物释放。有趣的是，发现小的穿孔对药物释放最不利，而具有大表面切口的包衣并没有完全失效。损坏的微丸包衣具有一定的自密封能力，且不会完全失效。因此，本研究深入了解了在缓释包衣微丸被破坏时包衣损坏对药物释放的影响。
