Kim Sangah, Cheikhali Mirna, Davé Rajesh N
New Jersey Center for Engineered Particulates, New Jersey Institute of Technology, Newark, New Jersey, 07102, USA.
Pharm Res. 2022 Dec;39(12):3079-3098. doi: 10.1007/s11095-022-03293-z. Epub 2022 Jun 14.
Fine API agglomeration and its mitigation via particle engineering, i.e., dry coating, remains underexplored. The purpose was to investigate agglomeration before and after dry coating of fine cohesive APIs and impact on powder processability, i.e., flowability (FFC), bulk density (BD), and dissolution of BCS Class II drugs.
Ibuprofen (three sizes), fenofibrate, and griseofulvin (5-20 µm), before and after dry coating with varying amounts of hydrophobic (R972P) or hydrophilic (A200) nano- silica, were assessed for agglomeration, FFC, BD, surface energy, wettability, and dissolution. The granular Bond number (Bo), a dimensionless parameter, evaluated through material-sparing particle-scale measures and particle-contact models, was used to express relative powder cohesion.
Significant powder processability improvements after dry coating were observed: FFC increased by multiple flow regimes, BD increased by 25-100%, agglomerate ratio (AR) reduction by over an order of magnitude, and greatly enhanced API dissolution rate even with hydrophobic (R972P) silica coating. Scrutiny of particle-contact models revealed non-triviality in estimating API surface roughness, which was managed through the assessment of measured bulk properties. A power-law correlation was identified between AR and Bo and subsequently, between AR and FFC & bulk density; AR below 5 ensured improved processability and dissolution.
Agglomeration, an overlooked material-sparing measure for powder cohesiveness, was a key indicator of powder processability and dissolution. The significant agglomerate reduction was possible via dry coating with either silica type at adequate surface area coverage. Reduced agglomeration after dry coating also countered the adverse impact of increased surface hydrophobicity on dissolution.
通过颗粒工程（即干包衣）实现的精细原料药团聚及其缓解方法仍未得到充分研究。本研究旨在调查精细粘性原料药干包衣前后的团聚情况及其对粉末加工性能的影响，即流动性（FFC）、堆密度（BD）以及BCS II类药物的溶出度。
对布洛芬（三种粒径）、非诺贝特和灰黄霉素（5 - 20 µm）在使用不同量的疏水性（R972P）或亲水性（A200）纳米二氧化硅进行干包衣前后，评估其团聚情况、FFC、BD、表面能、润湿性和溶出度。通过节省材料的颗粒尺度测量和颗粒接触模型评估的无量纲参数颗粒邦德数（Bo），用于表示相对粉末内聚力。
观察到干包衣后粉末加工性能有显著改善：FFC通过多种流动状态得到提高，BD增加了25 - 100%，团聚比（AR）降低了一个数量级以上，即使使用疏水性（R972P）二氧化硅包衣，原料药的溶出速率也大大提高。对颗粒接触模型的仔细研究表明，在估计原料药表面粗糙度方面存在复杂性，这通过对测量的整体性质进行评估来解决。确定了AR与Bo之间的幂律相关性，随后又确定了AR与FFC和堆密度之间的幂律相关性；AR低于5可确保加工性能和溶出度得到改善。
团聚是一种被忽视的用于衡量粉末内聚力的节省材料的方法，是粉末加工性能和溶出度的关键指标。通过在适当的表面积覆盖率下用任何一种二氧化硅类型进行干包衣，都有可能显著减少团聚。干包衣后团聚的减少也抵消了表面疏水性增加对溶出度的不利影响。
