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The possibility of attaining direct compression (DC) tableting using silica coated fine particle sized excipients was examined for high drug loaded (DL) binary blends of APIs. Three APIs, very-cohesive micronized acetaminophen (mAPAP, 7 μm), cohesive acetaminophen (cAPAP, 23 μm), and easy-flowing ibuprofen (IBU, 53 μm), were selected. High DL (60 wt%) binary blends were prepared with different fine-milled MCC-based excipients (ranging 20- 37 μm) with or without A200 silica coating during milling. The blend flowability (flow function coefficient −FFC) and bulk density (BD) of the blends for all three APIs were significantly improved by 1 wt% A200 dry coated MCCs; reaching FFC of 4.28 from 2.14, 7.82 from 2.96, and > 10 from 5.57, for mAPAP, cAPAP, and IBU blends, respectively, compared to the uncoated MCC blends. No negative impact was observed on the tablet tensile strength (TS) by using dry coated MCCs despite lower surface energy of silica. Instead, the desired tablet TS levels were reached or exceeded, even above that for the blends with uncoated milled MCCs. The novelty here is that milled and silica coated fine MCCs could promote DC tableting for cAPAP and IBU blends at 60 wt% DL through adequate flowability and tensile strength, without having to dry coat the APIs. The effect of the silica amount was investigated, indicating lesser had a positive impact on TS, whereas the higher amount had a positive impact on flowability. Thus, the finer excipient size and silica amounts may be adjusted to potentially attain blend DC processability for high DL blends of fine APIs.
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This content will become publicly available on December 1, 2025
Assessing processability of milled HME extrudates: Consolidating the effect of extrusion temperature, drug loading, and particle size via Non-dimensional cohesion
The downstream processability of Hot Melt Extrusion (HME) Amorphous Solid Dispersions (ASD), an underexplored topic of importance, was assessed through a multi-faceted particle engineering approach. Extrudates, comprised of griseofulvin (GF), a model poorly water-soluble drug, and hydroxypropyl cellulose (HPC), were prepared at four drug concentrations and three HME temperature profiles to yield cases with and without residual crystallinity and subsequently milled to five sieve cuts ranging from < 45 μm to 355 – 500 μm. Solid state characterization was performed with XRPD, FT-IR, and TGA. Particle scale properties of the milled extrudates were evaluated including particle size, density, surface energy, and morphologies imaged via SEM. It was observed that regardless of sieve cut size, drug concentration and HME conditions impacted the flowability trends, quantified via Flow Function Coefficient (FFC) and bulk density. As a novelty, the effects of various process parameters and drug loadings were consolidated into a dimensionless interparticle cohesion measure, granular Bond Number (Bog), to better correlate them with bulk powder properties. The significant contrast in particle morphologies, particle size, and densities among selected cases demonstrated that particle size alone should not be the sole consideration when correlating particle scale to bulk powder scale properties of milled extrudates. Instead, the HME temperature profile and ASD drug loading may be more suitable parameters affecting the bulk powder properties of the milled extrudates.
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- Award ID(s):
- 2137209
- PAR ID:
- 10572164
- Publisher / Repository:
- Elsevier
- Date Published:
- Journal Name:
- International Journal of Pharmaceutics
- Volume:
- 666
- Issue:
- C
- ISSN:
- 0378-5173
- Page Range / eLocation ID:
- 124833
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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