Enhanced blend uniformity and flowability of low drug loaded fine API blends via dry coating: The effect of mixing time and excipient size
Enhanced blend uniformity and flowability of low drug loaded fine API blends via dry coating: The effect of mixing time and excipient size
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通过干包衣增强低载药量精细 API 混合物的混合均匀性和流动性：混合时间和赋形剂尺寸的影响
DOI：
10.1016/j.ijpharm.2023.122722
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发表时间：
2023
影响因子：
5.8
通讯作者：
Davé, Rajesh N.
中科院分区：
文献类型：
--
作者：
Kim, Sangah S.;Castillo, Chelsea;Cheikhali, Mirna;Darweesh, Hadeel;Kossor, Christopher;Davé, Rajesh N.
尽管先前的研究证明了通过纳米颗粒干包衣改善了单个粉末的流动性、填充、流化等，但没有人考虑其对载药量非常低的混合物的影响。在此，在多组分共混物中使用1、3和5wt%载药量（DL）的精细布洛芬，以检查赋形剂尺寸、用亲水性或疏水性二氧化硅的干包衣以及混合时间对共混物均匀性、流动性和药物释放速率的影响。对于未包衣活性药物成分（API），无论辅料大小和混合时间如何，所有混合物的混合均匀度（BU）均较差。相比之下，对于具有低附聚物比率（AR）的干燥包衣的API，BU在较少的混合时间下显著改善，对于精细赋形剂共混物更是如此。对于干包衣的API，混合30分钟的精细赋形剂共混物具有增强的流动性和较低的AR;对于具有较少二氧化硅的最低DL更好，可能是由于混合诱导的二氧化硅再分布的协同作用。对于精细赋形剂片剂，干燥包衣导致快速API释放速率，即使使用疏水性二氧化硅包衣。值得注意的是，即使在非常低的DL和共混物中二氧化硅的量下，干燥包衣的API的低AR也导致了增强的共混物均匀性、流动性和API释放速率。
Although previous research demonstrated improved flowability, packing, fluidization, etc. of individual powders via nanoparticle dry coating, none considered its impact on very low drug loaded blends. Here, fine ibuprofen at 1, 3, and 5 wt% drug loadings (DL) was used in multi-component blends to examine the impact of the excipients size, dry coating with hydrophilic or hydrophobic silica, and mixing times on the blend uniformity, flowability and drug release rates. For uncoated active pharmaceutical ingredients (API), the blend uniformity (BU) was poor for all blends regardless of the excipient size and mixing time. In contrast, for dry coated API having low agglomerate ratio (AR), BU was dramatically improved, more so for the fine excipient blends, at lesser mixing times. For dry coated API, the fine excipient blends mixed for 30 min had enhanced flowability and lower AR; better for the lowest DL having lesser silica, likely due to mixing induced synergy of silica redistribution. For the fine excipient tablets, dry coating led to fast API release rates even with hydrophobic silica coating. Remarkably, the low AR of the dry coated API even at very low DL and amounts of silica in the blend led to the enhanced blend uniformity, flow, and API release rate.