Towards an improved understanding of drug excipient interactions to enable rapid optimization of nanosuspension formulations

Ferrar, Joseph A.; Sellers, Benjamin D.; Chan, Connie; Leung, Dennis

doi:10.1016/j.ijpharm.2020.119094

Cited by 35 publications

(26 citation statements)

References 39 publications

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“…The impact of excipients on the PSD and stability of indomethacin suspensions, although not specifically for LAS precipitation, has previously been reported. Ferrar et al performed a high throughput screening study using 28 excipients and combinations thereof to predict the most promising combinations to produce stable suspensions of indomethacin . The suspensions were made using a top-down approach, wet milling process, utilizing a resonant acoustic mixer .…”

Section: Resultsmentioning

confidence: 99%

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Impact of Excipients and Seeding on the Solid-State Form Transformation of Indomethacin during Liquid Antisolvent Precipitation

Silva

Kumar

Hodnett

et al. 2022

Crystal Growth & Design

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Long-acting injectables are a unique drug formulation strategy, providing a slow and sustained release of active pharmaceutical ingredients (APIs). In this study, a novel approach that combines liquid antisolvent precipitation with seeding to obtain a stable form of the API indomethacin while achieving the desired particle size distribution is described. It was proven that when a metastable form of indomethacin was initially nucleated, the rate of its transformation to the stable form was influenced by the presence of excipients and seeds (17.10 ± 0.20 μm), decreasing from 48 to 4 h. The final particle size (D50) of the indomethacin suspension produced without seeding was 7.33 ± 0.38 μm, and with seeding, it was 5.61 ± 0.14 μm. Additionally, it was shown that the particle size distribution of the seeds and the time point of seed addition were critical to obtain the desired solid-state form and that excipients played a crucial role during nucleation and polymorphic transformation. This alternative, energy-efficient bottom-up method for the production of drug suspensions with a reduced risk of contamination from milling equipment and fewer processing steps may prove to be comparable in terms of stability and particle size distribution to current industrially accepted top-down approaches.

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Section: Resultsmentioning

confidence: 99%

“…Currently, the selection of stabilizers for suspensions is based on a trial-and-error approach for both top-down and bottom-up approaches. However, to the best of our knowledge, a correlation in stabilizer selection for the two approaches has never been investigated. − …”

Section: Introductionmentioning

confidence: 99%

Impact of Excipients and Seeding on the Solid-State Form Transformation of Indomethacin during Liquid Antisolvent Precipitation

Silva

Kumar

Hodnett

et al. 2022

Crystal Growth & Design

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“…Hydrophilic molecules that contain electric charges can further stabilize drug nanocrystals through electrostatic repulsion between crystals, thereby providing sufficient space or charge stability for the drug nanocrystals. Ferrar et al (2020) investigated the effects of 28 stabilizer formulations on the formability of drug nanocrystals using three insoluble drugs as models and found that the key factors that affected the stability of the nanocrystals were the amphiphilicity of the stabilizer and whether it had a sufficiently long hydrocarbon chain. Through a molecular model, it is shown that surfactant molecules with long and flexible hydrophobic chains can anchor on the surfaces of nanocrystals more effectively, thereby increasing the stability.…”

Section: Hydrophilic and Hydrophobic Properties Of The Stabilizermentioning

confidence: 99%

Progress in the development of stabilization strategies for nanocrystal preparations

Wang

Zhang

et al. 2020

Drug Delivery

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In recent years, nanocrystal technology has been extensively investigated. Due to the submicron particle size and unique physicochemical properties of nanocrystals, they overcome the problems of low drug solubility and poor bioavailability. Although the structures of nanocrystals are simple, the further development of these materials is hindered by their stability. Drug nanocrystals with particle sizes of 1∼1000 nm usually require the addition of stabilizers such as polymers or surfactants to enhance their stability. The stability of nanocrystal suspensions and the redispersibility of solid nanocrystal drugs are the key factors for the large-scale production of nanocrystal preparations. In this paper, the factors that affect the stability of drug nanocrystal preparations are discussed, and related methods for solving the stability problem are put forward.

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“…These advantages have driven towards faster development of nanosuspension technology during last few decades [21]. Various methods are utilized for the formation of nanosuspension [22][23][24][25][26][27], including cosolvency [28], solid dispersion [29], inclusion complexation [30], cryogenic technique [31], salt formation [32], solvent-antisolvent method [33,34], supercritical fluid process [35], emulsification-solvent evaporation technique [36] and media milling techniques [37].…”

Section: Introductionmentioning

confidence: 99%

Comparative in vitro evaluation of glimepiride containing nanosuspension drug delivery system developed by different techniques

Bose

Sharma²,

Mishra

et al. 2021

Journal of Molecular Structure

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Towards an improved understanding of drug excipient interactions to enable rapid optimization of nanosuspension formulations

Cited by 35 publications

References 39 publications

Impact of Excipients and Seeding on the Solid-State Form Transformation of Indomethacin during Liquid Antisolvent Precipitation

Impact of Excipients and Seeding on the Solid-State Form Transformation of Indomethacin during Liquid Antisolvent Precipitation

Progress in the development of stabilization strategies for nanocrystal preparations

Comparative in vitro evaluation of glimepiride containing nanosuspension drug delivery system developed by different techniques

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