Physical Characterization of TRK-720 Hydrate, the Very Late Antigen-4 (VLA-4) Inhibitor, as a Solid Form for Inhalation: Preparation of the Hydrate by Solvent Exchange among Its Solvates and Mechanistical Considerations

Shiraki, Motohiro

doi:10.1002/jps.22246

Cited by 11 publications

(7 citation statements)

References 21 publications

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“…In most cases, the incorporation of lactose in the carrier is not for improved laryngeal adhesion of drugs but to enhance the powder flowability 26 , 27 . Lactose deposits in the larynx mainly due to its large particle size without drug loading capability 28 . Therefore, it is of great importance to develop the new carrier to achieve the targeted drug deposition and localization of the larynx.…”

Section: Introductionmentioning

confidence: 99%

Glycoside scutellarin enhanced CD-MOF anchoring for laryngeal delivery

Zhao

Guo

Wang

et al. 2020

Acta Pharmaceutica Sinica B

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It is essential to develop new carriers for laryngeal drug delivery in light of the lack of therapy in laryngeal related diseases. When the inhalable micron-sized crystals of γ -cyclodextrin metal-organic framework (CD-MOF) was utilized as dry powder inhalers (DPIs) carrier with high fine particle fraction (FPF), it was found in this research that the encapsulation of a glycoside compound, namely, scutellarin (SCU) in CD-MOF could significantly enhance its laryngeal deposition. Firstly, SCU loading into CD-MOF was optimized by incubation. Then, a series of characterizations were carried out to elucidate the mechanisms of drug loading. Finally, the laryngeal deposition rate of CD-MOF was 57.72 ± 2.19% improved by SCU, about two times higher than that of CD-MOF, when it was determined by Next Generation Impactor (NGI) at 65 L/min. As a proof of concept, pharyngolaryngitis therapeutic agent dexamethasone (DEX) had improved laryngeal deposition after being co-encapsulated with SCU in CD-MOF. The molecular simulation demonstrated the configuration of SCU in CD-MOF and its contribution to the free energy of the SCU@CD-MOF, which defined the enhanced laryngeal anchoring. In conclusion, the glycosides-like SCU could effectively enhance the anchoring of CD-MOF particles to the larynx to facilitate the treatment of laryngeal diseases.

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Section: Introductionmentioning

confidence: 99%

Glycoside scutellarin enhanced CD-MOF anchoring for laryngeal delivery

Zhao

Guo

Wang

et al. 2020

Acta Pharmaceutica Sinica B

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“…The stability of hydrates can vary significantly, and their transformation behavior and interrelationship with other solid forms of the same compound (anhydrates, lower/higher hydrates, etc.) should be extensively studied − , to avoid problems related to the material properties of the substance. Generally, hydrates are susceptible to dehydration during routine drying or storage conditions, which may lead to the formation of a hydrate with lower water content, a dehydrated hydrate, one or more anhydrous forms (polymorphs) or an amorphous material.…”

Section: Introductionmentioning

confidence: 99%

Stoichiometric and Nonstoichiometric Hydrates of Brucine

Braun

Griesser

2016

Crystal Growth & Design

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The complex interplay of temperature and water activity (aw)/relative humidity (RH) on the solid form stability and transformation pathways of three hydrates (HyA, HyB, and HyC), an isostructural dehydrate (HyAdehy), an anhydrate (AH), and amorphous brucine has been elucidated and the transformation enthalpies quantified. The dihydrate (HyA) shows a nonstoichiometric (de)hydration behavior at RH < 40% at 25 °C, and the removal of the water molecules results in an isomorphic dehydrate structure. The metastable dehydration product converts to AH upon storage at the driest conditions or to HyA if exposed to moisture. HyB is a stoichiometric tetrahydrate. The loss of the water molecules causes HyB to collapse to an amorphous phase. Amorphous brucine transforms to AH at RH < 40% RH and a mixture of hydrated phases at higher RH values. The third hydrate (HyC) is only stable at RH ≥ 55% at 25 °C and contains 3.65–3.85 mol equiv of water. Dehydration of HyC occurs in one step at RH < 55% at 25 °C or upon heating, and AH is obtained. The AH is the thermodynamically most stable phase of brucine at RH < 40% at 25 °C. Depending on the conditions, temperature, and aw, each of the three hydrates becomes the thermodynamically most stable form. This study demonstrates the importance of applying complementary analytical techniques and appropriate approaches for understanding the stability ranges and transition behavior between the solid forms of compounds with multiple hydrates.

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“…128 The dihydrate and two anhydrate forms of 5,11-dihydro-11-ethyl-5-methyl-8-(2-(1-oxido-4-quinolinyl)ethyl-6H-dipyrido(3,2-B:2 , 3 -E)(1,4)diazepin-6-one have been studied by solidstate 13 C NMR to obtain information on molecular mobility and the degree of crystallinity. 129 In addition, mixtures of multiple forms could be detected on the basis of chemical shift patterns and relaxation measurements.…”

Section: Solvatomorphic Systemsmentioning

confidence: 99%