Enhanced blend uniformity and flowability of low drug loaded fine API blends via dry coating: The effect of mixing time and excipient size

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.

Highlights

• Normalized API agglomeration, is a governing parameter for blend properties.

• Dry coating reduces mixing time and size disparity effect on blend uniformity (BU)

• Lesser the silica, the better the synergic flow enhancement of low drug loaded blends.

• For dry coated fine API blends, fine excipients better than coarse excipients.

• Reduced AR via dry coating enhances BU, flow, and dissolution even for R972P silica.

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.

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Sangah S. Kim, Chelsea Castillo, Mirna Cheikhali, Hadeel Darweesh, Christopher Kossor, Rajesh N. Davé,
Enhanced blend uniformity and flowability of low drug loaded fine API blends via dry coating: The effect of mixing time and excipient size, International Journal of Pharmaceutics, Volume 635, 2023, 122722, ISSN 0378-5173, https://doi.org/10.1016/j.ijpharm.2023.122722.