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超细微包覆布洛芬的流动和压实行为。

Flow and compaction behaviour of ultrafine coated ibuprofen.

机构信息

Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Sector-67, S.A.S. Nagar, Mohali, Punjab, India.

出版信息

Int J Pharm. 2013 Jan 30;441(1-2):527-34. doi: 10.1016/j.ijpharm.2012.10.048. Epub 2012 Nov 8.

Abstract

Good flow and compaction properties are prerequisites for successful compaction process. Apart from initial profile, mechanical properties of pharmaceutical powders can get modified during unit processes like milling. Milled powders can exhibit a wide range of particle size distribution. Further downstream processing steps like compaction can be affected by this differential particle size distribution. This has greatest implications for formulations like high dose drugs wherein the active pharmaceutical ingredient (API) contributes the maximum bulk in the final formulation. The present study assesses the impact of dry coating with ultrafine particles of same material, on the flow and compaction properties of the core material. Ibuprofen was selected as model drug as it has been reported to have poor mechanical properties. Ultrafine ibuprofen (average size 1.75 μm) was generated by Dyno(®) milling and was dry coated onto the core ibuprofen particles (average size 180 μm). Compaction studies were performed using a fully instrumented rotary tablet press. Compaction data was analyzed for compressibility, tabletability, compactibility profiles and Heckel plot. Dry coating of the ibuprofen exhibited greater compressibility and tabletability, at lower compaction pressure. However, at compaction pressure above 220 MPa, compressibility and tabletability of coated as well as uncoated materials were found to be similar. Heckel analysis also supported the above findings, as P(y) value of uncoated ibuprofen was found to be 229.49 MPa and for 2.0% ultrafine coated ibuprofen was found to be 158.53 MPa. Lower P(y) value of ultrafine coated ibuprofen indicated ease of plastic deformation. Superior compressibility and deformation behaviour of ultrafine coated ibuprofen attributed to increased interparticulate bonding area. This strategy can also be explored for improving tabletability of high dose poorly compressible drugs.

摘要

良好的流动性和紧实度是成功压实过程的前提条件。除了初始形态外,药物粉末的机械性能在研磨等单元操作过程中也可能发生变化。研磨后的粉末可能表现出广泛的粒径分布。进一步的下游加工步骤,如压实,可能会受到这种差异粒径分布的影响。这对高剂量药物等制剂的影响最大,其中活性药物成分(API)在最终制剂中占最大比例。本研究评估了用相同材料的超细颗粒进行干法包衣对芯材流动性和压实性能的影响。布洛芬被选为模型药物,因为它被报道具有较差的机械性能。超细微布洛芬(平均粒径 1.75μm)是通过 Dyno®(R)研磨生成的,并被干法包衣到核心布洛芬颗粒(平均粒径 180μm)上。使用全仪器化旋转压片机进行压实研究。对压缩性、可压性、压实性曲线和 Heckel 图进行了分析。布洛芬的干法包衣表现出更高的压缩性和可压性,在较低的压实压力下。然而,在压实压力高于 220MPa 时,涂层和未涂层材料的压缩性和可压性被发现相似。 Heckel 分析也支持了上述发现,因为未涂层布洛芬的 P(y) 值为 229.49MPa,而 2.0%超细微涂层布洛芬的 P(y) 值为 158.53MPa。超细微涂层布洛芬的较低 P(y) 值表明其易于发生塑性变形。超细微涂层布洛芬具有更好的压缩性和变形行为,这归因于增加了颗粒间的结合面积。这种策略也可以探索用于改善高剂量难以压缩药物的可压性。

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