A multivariate approach to predict the volumetric and gravimetric feeding behavior of a low feed rate feeder based on raw material properties

Bostijn, N.; Dhondt, Jens; Ryckaert, Alexander; Szabó, Edina; Dhondt, W.; Snick, B. Van; Vanhoorne, Valérie; Beer, Thomas De

doi:10.1016/j.ijpharm.2018.12.066

Cited by 62 publications

(30 citation statements)

References 24 publications

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“…However, continuous low-dose feeding is increasingly important for two reasons: first, the pharmaceutical industry is in the process of adopting continuous manufacturing. Second, high-potency active pharmaceutical ingredients (HPAPIs), with doses in the range of milligrams or even micrograms per tablet, are becoming more frequent ( 9 – 11 ). Currently, no reliable equipment exists that can be used for continuous low-dose feeding of powders ( 12 – 16 ).…”

Section: Introductionmentioning

confidence: 99%

Performance Evaluation of a High-Precision Low-Dose Powder Feeder

et al. 2020

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Highly potent active pharmaceutical ingredients (APIs) and low-dose excipients, or excipients with very low density, are notoriously hard to feed with currently available commercial technology. The micro-feeder system presented in this work is capable of feeding low-dose rates of powders with different particle sizes and flow properties. Two different grades of lactose, di-calcium phosphate, croscarmellose sodium, silicon dioxide, a spray-dried intermediate, and an active ingredient were studied to vary material properties to test performance of the system. The current micro-feeder system is a volumetric feeder combined with a weighing balance at the outlet that measures feeder output rates. Feeding results are shown as a so-called “displacement-feed factor” curve for each material. Since the powder mass and volume are known in the micro-feeder system, in this work, we characterized an observed density variation during processing via a “displacement-feed factor” profile for each of the fed powders. This curve can be later used for calibrating the system to ensure an accurate, constant feed rate and in addition predicting feeding performance for that material at any feed rate. There is a relation between powder properties and feeding performance. Powders with finer particles and higher compressibility show densification during their feeding process. However, powders with larger particles and lower compressibility show both “densification” and “powder bed expansion,” which is the manifestation of dilation and elastic recovery of particles during the micro-feeding process. Through the application of the displacement-feed factor, it is possible to provide precise feeding accuracy of low-dose materials. Graphical abstract

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Section: Introductionmentioning

confidence: 99%

Performance Evaluation of a High-Precision Low-Dose Powder Feeder

et al. 2020

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“…However, Pearl300_SC demonstrated better flow when compared to the raw and wetsieved materials. Improvement in flow has been associated with more consistency during powder filling (42) and could potentially explain the observed results. Still, Pearl300_SC showed a larger intra-device variability (RSD~6%).…”

Section: Impact Of Particle Engineering On Shot Weight Consistencymentioning

confidence: 84%

“…We hypothesize, that this was mainly related to the spherical shape of the spray-congealed material. Spherical shaped materials are known to pack more uniformly compared to irregular ones, so for the same recess volume a higher powder mass could be dispensed (41,42). Additionally, it was observed that for Pearl300_SC the two devices tested showed extremely identical performances.…”

Section: Impact Of Particle Engineering On Shot Weight Consistencymentioning

confidence: 96%

Spray-Congealing and Wet-Sieving as Alternative Processes for Engineering of Inhalation Carrier Particles: Comparison of Surface Properties, Blending and In Vitro Performance

et al. 2021

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Purpose Traditionally, α-lactose monohydrate is the carrier of choice in dry powder inhaler (DPI) formulations. Nonetheless, other sugars, such as D-mannitol, have emerged as potential alternatives. Herein, we explored different particle engineering processes to produce D-mannitol carriers for inhaled delivery. Methods Wet-sieving and spray-congealing were employed as innovative techniques to evaluate the impact of engineering on the particle properties of D-mannitol. To that end, the resulting powders were characterized concerning their solid-state, micromeritics and flowability. Afterwards, the engineered carrier particles were blended with inhalable size beclomethasone dipropionate to form low dose (1 wt%) DPI formulations. The in vitro aerosolization performance was evaluated using the NEXThaler®, a reservoir multi-dose device. Results Wet-sieving generated D-mannitol particles with a narrow particle size distribution and spray-congealing free-flowing spherical particles. The more uniform pumice particles with deep voids and clefts of wet-sieved D-mannitol (Pearl300_WS) were beneficial to drug aerosolization, only when used in combination with a ternary agent (10 wt% of ‘Preblend’). When compared to the starting material, the spray-congealed D-mannitol has shown to be promising in terms of the relative increase of the fine particle fraction of the drug (around 100%), when used without the addition of ternary agents. Conclusions The wet-sieving process and the related aerosolization performance are strongly dependent on the topography and structure of the starting material. Spray-congealing, has shown to be a potential process for generating smooth spherical particles of D-mannitol that enhance the in vitro aerosolization performance in binary blends of the carrier with a low drug dose.

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“…As a result, this dataset can facilitate the development of formulations and pharmaceutical dry powder processes became designable by building predictive models based on the descriptors. Bostijn et al, gave an excellent example to the applicability of this database via investigating the feeding of 15 different powders (including APIs) by low feeding rate [95]. The main conclusion of the article was that less feeding experiments would be necessary by following the presented approach and thus, the raw material consumption would also decrease during new drug development.…”

Section: Powder Characterizationmentioning

confidence: 99%

Continuous Formulation Approaches of Amorphous Solid Dispersions: Significance of Powder Flow Properties and Feeding Performance

et al. 2019

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Preparation and formulation of amorphous solid dispersions (ASDs) are becoming more and more popular in the pharmaceutical field because the dissolution of poorly water-soluble drugs can be effectively improved this way, which can lead to increased bioavailability in many cases. During downstream processing of ASDs, technologists need to keep in mind both traditional challenges and the newest trends. In the last decade, the pharmaceutical industry began to display considerable interest in continuous processing, which can be explained with their potential advantages such as smaller footprint, easier scale-up, and more consistent product, better quality and quality assurance. Continuous downstream processing of drug-loaded ASDs opens new ways for automatic operation. Therefore, the formulation of poorly water-soluble drugs may be more effective and safe. However, developments can be challenging due to the poor flowability and feeding properties of ASDs. Consequently, this review pays special attention to these characteristics since the feeding of the components greatly influences the content uniformity in the final dosage form. The main purpose of this paper is to summarize the most important steps of the possible ASD-based continuous downstream processes in order to give a clear overview of current course lines and future perspectives.

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A multivariate approach to predict the volumetric and gravimetric feeding behavior of a low feed rate feeder based on raw material properties

Cited by 62 publications

References 24 publications

Performance Evaluation of a High-Precision Low-Dose Powder Feeder

Performance Evaluation of a High-Precision Low-Dose Powder Feeder

Spray-Congealing and Wet-Sieving as Alternative Processes for Engineering of Inhalation Carrier Particles: Comparison of Surface Properties, Blending and In Vitro Performance

Continuous Formulation Approaches of Amorphous Solid Dispersions: Significance of Powder Flow Properties and Feeding Performance

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