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Characterising Powder Flow Properties for Pharmaceutical Applications

The pharmaceutical industry is a continually evolving sector, with requirements to consistently improve efficiency while maintaining product quality. Understanding and controlling powder behaviour is a major focus for effective processing.


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The complexities of powder behaviour are reflected in the varied studies carried out by FT4 Powder Rheometer® users. Over the last decade, there has been increased recognition that in order to fully understand powder behaviour, a multifaceted approach, which examines a diverse range of powder properties, is needed.

The papers below highlight a variety of processing challenges, and how powder testing can be used to identify properties to optimise pharmaceutical processes.

“Elucidating the Effect of Fine Lactose Ratio on the Rheological Properties and Aerodynamic Behavior of Dry Powder for Inhalation”

Ying Sun, Lu Qin, Jiayi Li, Jian Su, Ruxiao Song, Xin Zhang, Jian Guan, Shirui Mao | School of Pharmacy, Shenyang Pharmaceutical University

AAPS Journal | April 2021


Dry powder inhaler (DPI) is recognized as the first choice for lung diseases' treatment. However, it lacks a universal way for DPI formulation development. Fine lactose is commonly added in DPIs to improve delivery performance; however, the fine ratio-dependent mechanism is unclear. Therefore, the objective of this study is to explore the influence of fine lactose ratio on DPI powder properties and aerodynamic behavior, and the fine lactose ratio-dependent mechanism involved during powder fluidization and lung deposition. Here salbutamol sulfate was used as a model drug, Lactohale® 206 as coarse carrier, and Lactohale® 300 as fine component; the mixtures were prepared at 1% drug content, with fine content up to 20%. It was shown that with the fine addition, flowability of the mixtures was improved, interaction among particles was increased, and the presence of fines could help to improve DPI's aerosolization performance. When the fines added were less than 3%, the "active site" hypothesis played a leading role. When the added fines were over 3% but less than 10%, fluidization enhancement mechanism was more important. After the added fines reaching 10%, aggregate mechanism started to dominate. However, FPF cannot be further increased once the fines reached 20%. Moreover, the correlations between FPF and dynamic powder parameters were verified in ternary mixtures, and cohesion had a greater impact on FPF than that of flowability. In conclusion, adding lactose fines is an effective way to improve lung deposition of DPI, with the concrete mechanism lactose fine ratio dependent.

“Tailoring Crystal Size Distributions for Product Performance, Compaction of Paracetamol”

Leila Keshavarz, Mahboubeh Pishnamazi, U.B. Rao Khandavilli, Saeed Shirazian, Maurice N. Collins, Gavin M. Walker, Patrick J. Frawley | Synthesis and Solid State Pharmaceutical Centre (SSPC), Bernal Institute, University of Limerick, Ireland; Laboratory of Computational Modeling of Drugs, South Ural State University, Russia; Stokes Laboratories, Bernal Institute, University of Limerick, Ireland; Health Research Institute, University of Limerick, Ireland

Arabian Journal of Chemistry | 23 February 2021


Paracetamol crystals often exhibit poor compressibility properties, which results in capping issues. The Particle Size Distribution (PSD) of paracetamol was engineered to improve the compressibility of paracetamol crystals. This was accomplished by growing paracetamol crystals in the presence of additives. The active pharmaceutical ingredient Phenacetin and impurity 4-chloroacetanalide were used to modify the crystal properties of paracetamol. In solution, the phenacetin or 4-chloroacetanalide molecules adsorb onto the paracetamol crystal faces selectively (110 or 011) and inhibit the further growth of the paracetamol crystal and consequently, the paracetamol crystal growth is reduced substantially. For controlling the PSD of crystal to improve the compressibility of paracetamol crystals, a set of cooling crystallization experiments in the presence of additive was designed. According to a statistical experimental design, the cooling rate was the most effective parameter. The PSD was reduced when paracetamol crystallized from the controlled crystallization in the presence of less than 3 mol% of both additives. These smaller particles increased almost four-fold the compressibility of paracetamol in comparison to the commercial material. Moreover, tablets were prepared for each formulation using a direct compaction method. The results illustrated that a higher tablet hardness of paracetamol was achieved by tailoring the paracetamol crystal size distribution. In addition, the tablet disintegration time was higher for the formulation with increased hardness. Overall, this work presents the potential use of structurally similar compounds as additives to alter the mechanical properties of an API.

“Understanding Carrier Performance in Low-Dose Dry Powder Inhalation: An In Vitro–In Silico Approach”

Joana T. Pinto, Inês Cachola, João F. Pinto, and Amrit Paudel | Research Center Pharmaceutical Engineering GmbH, Austria; iMed.ULisboa–Research Institute for Medicines, Faculdade de Farmácia, Universidade de Lisboa, Portugal; Institute of Process and Particle Engineering, Graz University of Technology, Austria

Pharmaceutics | 24 February 2021


The use of physiologically based pharmacokinetic (PBPK) models to support drug product development has become increasingly popular. The in vitro characterization of the materials of the formulation provides valuable descriptors for the in silico prediction of the drug’s pharmacokinetic profile. Thus, the application of an in vitro–in silico framework can be decisive towards the prediction of the in vivo performance of a new medicine. By applying such an approach, this work aimed to derive mechanistic based insights into the potential impact of carrier particles and powder bulk properties on the in vivo performance of a lactose-based dry powder inhaler (DPI). For this, a PBPK model was developed using salbutamol sulphate (SS) as a model drug and the in vitro performance of its low-dose blends (2% w/w) with different types of lactose particles was investigated using different DPI types (capsule versus reservoir) at distinct airflows. Likewise, the influence of various carrier’s particle and bulk properties, device type and airflow were investigated in silico. Results showed that for the capsule-based device, low-dose blends of SS had a better performance, when smaller carrier particles (Dv0.5 50 μm) with about 10% of fines were used. This resulted in a better predicted bioavailability of the drug for all the tested airflows. For the reservoir type DPI, the mean particle size (Dv0.5) was identified as the critical parameter impacting performance. Shear cell and air permeability or compressibility measurements, particle size distribution by pressure titration and the tensile strength of the selected lactose carrier powders were found useful to generate descriptors that could anticipate the potential in vivo performance of the tested DPI blends.

“Starch Products as Candidate Excipients in a Continuous Direct Compression Line”

Sonia M. Razavi, Yi Tao, James Scicolone, Tami Morker, Charles Cunningham, Ali Rajabi-Siahboomi, Douglas B. Hausner & Fernando J. Muzzio | C-SOPS, Department of Chemical and Biochemical Engineering, Rutgers University, USA; Colorcon, USA

Journal of Pharmaceutical Innovation | 23 September 2020


Direct compression (DC) remains the most preferred technique to produce tablets, and its effectiveness is directly influenced by raw material attributes. Therefore, the selection of specific grades of excipients to achieve desirable powder flow and compression properties is of importance. Shifting toward continuous manufacturing requires even more enhanced performance, quality, and consistency directly from the starting ingredients. Starch, as a well-known excipient with good compression characteristics in its native state, is poorly flowing and highly sensitive to lubrication. The objective of this study was to characterize the flow properties of different starch products and investigate the suitability of modified starch products for continuous manufacturing.

“Evaluation of Multifunctional Magnesium Aluminosilicate Materials as Novel Family of Glidants in Solid Dosage Products”

D.T. Tran, P. Komínová, L. Kulaviak, P. Zámostný | Department of Organic Technology, Faculty of Chemical Technology, University of Chemistry and Technology, Czech Republic; Department of Multiphase Reactors, Institute of Chemical Process Fundamentals of the ASCR, Czech Republic

International Journal of Pharmaceutics | 8 November 2020


The work was aimed at evaluating the efficiency of multifunctional magnesium aluminosilicate materials (MAS) as a novel glidant in solid dosage forms. MAS are known for their very low cohesive interactions and their utilization could avoid the disadvantages associated with conventional glidant usage. Flow properties of several mixtures comprising a model excipient (microcrystalline cellulose) and a glidant were characterized using a powder rheometer FT4. The mixtures were formulated to represent effects of glidant types, various levels of glidant loading, particle size and mixing time on flow properties of the model excipient. Pre-conditioning, shear testing, compressibility, flow energy measurements and an additional tapping test were carried out to monitor flow properties. Mixtures were analyzed employing scanning electron microscopy, using a detector of back-scattered electrons to identify a mechanism of MAS towards improving the mixture flow properties. All studied parameters were found to have substantial effects on mixture flow properties, but the effect of mixing time was much less important compared to mixtures based on traditional glidant. The mechanism of MAS glidant action was found to be different compared to that of traditional one, having less process sensitivity, so that MAS utilization as glidant could be advantageous for the formulation performance.


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