Predictive selection of silica size, type (hydrophobic/hydrophilic), and amount is addressed for achieving significant property enhancements of fine active pharmaceutical ingredients (APIs). Four models, Chen’s multiasperity particle-adhesion, total surface energy-based guest-host compatibility, dispersive surface energy-based tablet tensile strength, and stick-bounce-based silica aggregation on coated particles, are invoked. The impact on the bulk properties of four APIs cohesive API powders (~10 μm) and 40 wt% (wt%) blends of one API, drycoated at 50% and 100% surface area coverage (SAC) of four nano-silicas (7–20 nm), hydrophobic (R972P),
hydrophilic (M5P, A200, A300) is assessed. Significant enhancements in flowability, bulk density, compactability,
agglomeration reduction, and dissolution for API or blend are achieved with all silicas. The experimental
and model-based outcomes demonstrate that silica performance is impacted by multiple factors, silica size and
coating effectiveness being most critical. In conclusion, R972P and A200 at lower 50% SAC present two excellent choices.
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Decoding Fine API Agglomeration as a Key Indicator of Powder Flowability and Dissolution: Impact of Particle Engineering
Purpose: 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.
Method: 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 (Bog), a dimensionless parameter, evaluated through material-sparing particle-scale measures and particle-contact models, was used to express relative powder cohesion.
Results: 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 Bog and subsequently, between AR and FFC & bulk density; AR below 5 ensured improved processability and dissolution.
Conclusion: 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.
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- NSF-PAR ID:
- 10340802
- Date Published:
- Journal Name:
- Pharmaceutical Research
- ISSN:
- 0724-8741
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Purpose: To investigate the effect of dry coating the amount and type of silica on powder flowability enhancement using a comprehensive set of 19 pharmaceutical powders having different sizes, surface roughness, morphology, and aspect ratios, as well as assess flow predictability via Bond number estimated using a mechanistic multi-asperity particle contact model. Method: Particle size, shape, density, surface energy and area, SEM-based morphology, and FFC were assessed for all powders. Hydrophobic (R972P) or hydrophilic (A200) nano-silica were dry coated for each powder at 25%, 50%, and 100% surface area coverage (SAC). Flow predictability was assessed via particle size and Bond number. Results: Nearly maximal flow enhancement, one or more flow category, was observed for all powders at 50% SAC of either type of silica, equivalent to 1 wt% or less for both the hydrophobic R972P or hydrophilic A200, while R972P generally performed slightly better. Silica amount as SAC better helped understand the relative performance. The power-law relation between FFC and Bond number was observed. Conclusion: Significant flow enhancements were achieved at 50% SAC, validating previous models. Most uncoated very cohesive powders improved by two flow categories, attaining easy flow. Flowability could not be predicted for both the uncoated and dry coated powders via particle size alone. Prediction was significantly better using Bond number computed via the mechanistic multi-asperity particle contact model accounting for the particle size, surface energy, roughness, and the amount and type of silica. The widely accepted 200 nm surface roughness was not valid for most pharmaceutical powders.more » « less
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Digital image correlation (DIC) is a non-destructive and non-contact optical technique to measure deformation and strain of materials. The method is based on optically tracking the displacements of a speckle pattern created on the material surface. In the case of soft tissues such as mouse aorta, there are several advantages to using DIC since it can provide local, rather than global, deformations and it is suitable for large strain measurements, typical of soft tissues taken to failure [1] [2]. For the optimal use of DIC, several requirements should be met for speckle patterning: 1) randomness, 2) high contrast, 3) appropriate size of speckle in the field of view (3-5 pixels), and 4) firm attachment of speckle to specimen during deformation. In previous DIC studies of soft tissues, the methods employed to create a speckle pattern include the use of an airbrush to spray dye or paint on the specimen, or coating the sample with toner powder. However, biological samples must be partially dehydrated before applying paint which may affect the mechanical properties of the specimen, and toner powder is too hydrophobic to adhere well on specimens when submerged in aqueous solution during mechanical testing. In addition, it is difficult to evenly distribute paint or toner powder on the surface of a hydrated biological specimen [2]. Therefore, a novel method utilizing colloidal gold particles to create a speckle pattern on mouse aorta is proposed in this work.more » « less
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In this study, hydrophilic silica nanoparticles (Si NPs) were used to modify α-alumina tubular membranes to improve their performance in terms of flux, oil rejection, and anti-fouling properties. Our work focuses on enhancing membrane performance, particularly for difficult applications such as produced water treatment. The prepared membranes were applied for oil-in-water emulsion treatment. After coating hydrophilic Si NPs, the oil contact angle improved from 133.8° to 171.4°. To prevent Si NPs from leaching off the surface of α-alumina tubular membranes, polyvinyl alcohol was used to coat the membranes as a pre-treatment step before Si NP modification. After coating the membrane with Si NPs, the roughness of the membrane surface decreased, likely leading to less fouling. After coating Si NPs, Total Organic Carbon rejection increased from 93.1% for pristine α-alumina tubular membranes to 97.7% for silica-modified membranes because of hydrophilic improvements of the modified membranes. The Si NP coating improved the anti-fouling property of membranes with the flux recovery ratio increasing from 71.3% for pristine α-alumina tubular membranes to 85.9% for silica-modified membranes. Scanning Electron Microscopy, Energy- dispersive X-ray spectroscopy, oil contact angle, and Atomic Force Microscopy characterization tests were done. The tests showed successful Si NPs impregnation and altered wettability.more » « less
- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1007/s11095-022-03293-z
