Analytical method development for powder characterization: Visualization of the critical drug loading affecting the processability of a formulation for direct compression

Hirschberg, Cosima; Sun, Changquan Calvin; Rantanen, Jukka

doi:10.1016/j.jpba.2016.06.014

Cited by 22 publications

(7 citation statements)

References 35 publications

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“…particle size and morphology). API particles typically have a small particle size relative to excipient particles (Bellamy et al, 2008;Olusanmi et al, 2014) and frequently exhibit a needle-like shape (Tye et al, 2005;Waknis et al, 2013), which can result in poor powder flowability (Carstensen and Chan, 1976, Hart, 2016, Hirschberg, Sun and Rantanen, 2016, segregation (Olusanmi et al, 2014), and unwanted adhesion to surfaces (e.g. tablet punches) (Lam and Newton, 1992, Paul et al, 2017a, Paul et al, 2017b.…”

Section: Introductionmentioning

confidence: 99%

Characterisation of pore structures of pharmaceutical tablets: A review

Markl

Strobel

Schlossnikl

et al. 2018

International Journal of Pharmaceutics

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107

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Traditionally, the development of a new solid dosage form is formulation-driven and less focus is put on the design of a specific microstructure for the drug delivery system. However, the compaction process particularly impacts the microstructure, or more precisely, the pore architecture in a pharmaceutical tablet. Besides the formulation, the pore structure is a major contributor to the overall performance of oral solid dosage forms as it directly affects the liquid uptake rate, which is the very first step of the dissolution process. In future, additive manufacturing is a potential game changer to design the inner structures and realise a tailor-made pore structure. In pharmaceutical development the pore structure is most commonly only described by the total porosity of the tablet matrix. Yet it is of great importance to consider other parameters to fully resolve the interplay between microstructure and dosage form performance. Specifically, tortuosity, connectivity, as well as pore shape, size and orientation all impact the flow paths and play an important role in describing the fluid flow in a pharmaceutical tablet. This review presents the key properties of the pore structures in solid dosage forms and it discusses how to measure these properties. In particular, the principles, advantages and limitations of helium pycnometry, mercury porosimetry, terahertz time-domain spectroscopy, nuclear magnetic resonance and X-ray computed microtomography are discussed.

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Section: Introductionmentioning

confidence: 99%

Characterisation of pore structures of pharmaceutical tablets: A review

Markl

Strobel

Schlossnikl

et al. 2018

International Journal of Pharmaceutics

Self Cite

107

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“…Performing flowability assessment of an API early in product development is therefore recommended. This can be carried out with the availability of material-sparing instruments. , For instance, in our case, flow property evaluation only needs 3–8 g of powder depending on the bulk density. The results of flowability assessment showed when 5-ASA crystals gradually became more isotropic (aspect ratio > 0.5) and larger (Table ), the powder flow improved as indicated by high values of flow parameters.…”

Section: Resultsmentioning

confidence: 99%

Downstream Processability of Crystal Habit-Modified Active Pharmaceutical Ingredient

Pudasaini

Upadhyay

Parker³

et al. 2017

Org. Process Res. Dev.

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Efficient downstream processing of active pharmaceutical ingredients (APIs) can depend strongly on their particulate properties, such as size and shape distributions. Especially in drug products with high API content, needle-like crystal habit of an API may show compromised flowability and tabletability, creating significant processability difficulties on a production scale. However, such a habit can be adapted to the needs of downstream processing. To this end, we modified the needle-like crystal habit of the model API 5-aminosalicylic acid (5-ASA). This study reports processability assessment of six representative crystal habits of 5-ASA (needles, plates, rectangular bars, rhombohedrals, elongated hexagons, and spheroids) in the context of direct compression using ring shear tester, flow rate analyzer, and instrumented tablet press. As expected, needles were very cohesive, had low flow rate (1.0 ± 0.08 mg/s), and low bulk density (0.14 ± 0.01 g/mL) but showed better tabletability, whereas the opposite was observed with more isotropic crystal habits. For instance, spheroids, elongated hexagons, and rhombohedrals were easy/free-flowing and had high bulk densities (≥0.5 g/mL), but final tablets had lower tensile strength than that of needles. Of the six crystal habits, the plates showed a good compromise considering both flowability and tabletability.

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“…Therefore, it is necessary to study the behavior of raw materials in powdered form to understand how they will affect the quality of the medicament. In this respect, knowledge of the flow properties of powders is very important in pre-formulation tests, to allow predicting the behavior of the particles and optimize the production process with consequent reduction of operating costs [49,50].…”

Section: Analysis Of Flow Propertiesmentioning

confidence: 99%

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2017

JPSA

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Entangled states are crucial to quantum computation and quantum communication, and are usually treated as the target states to be accessed by quantum control methods. While most of the researches focus on the generation of the desired entangled state at the terminal state , this paper considers the time-varying entanglement of the transient state | throughout the qubit transfer process. It is found that the degree of entanglement of | determines how fast and accurately the terminal state can be achieved. Four quantitative indices of entanglement are employed here to evaluate the degree of entanglement of | and to estimate the qubit control performance resulting from different control gains in the Lyapunov control law. Our results show that increasing the degree of entanglement during the qubit transfer process is helpful to improve the convergence to the target state; however, increasing control gain tends to destroy the entanglement and attenuate the multi-qubit transfer efficiency. The lack of sufficient quantum correlation between some initial state | and terminal state is the main reason for unavailable qubit transfer between them. For these states, the insertion of an intermediate entangled state | can effectively increase the degree of entanglement and help to realize the qubit transfer | via the transition processs | | .Keywords: Qubit quantum control, entangled state, index of quantum entanglement.

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Analytical method development for powder characterization: Visualization of the critical drug loading affecting the processability of a formulation for direct compression

Cited by 22 publications

References 35 publications

Characterisation of pore structures of pharmaceutical tablets: A review

Characterisation of pore structures of pharmaceutical tablets: A review

Downstream Processability of Crystal Habit-Modified Active Pharmaceutical Ingredient

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