Physical stability and dissolution behaviors of amorphous pharmaceutical solids: Role of surface and interface effects

Shi, Qin; Moinuddin, Sakib M.; Wang, Yanan; Ahsan, Fakhrul; Li, Fang

doi:10.1016/j.ijpharm.2022.122098

Cited by 15 publications

(11 citation statements)

References 84 publications

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“…However, some studies have reported that the bulk diffusion-controlled growth model is invalid in some amorphous solids as temperature decreases near or below T g [ 1 , 8 ]. One growth mode, termed the glass-to-crystal (GC) mode, has been reported in some organic molecules [ 1 , 9 , 10 ]. Upon decreasing the temperature near or below T g , a sudden increase in the crystal growth rate can be observed [ 8 , 9 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

“…One growth mode, termed the glass-to-crystal (GC) mode, has been reported in some organic molecules [ 1 , 9 , 10 ]. Upon decreasing the temperature near or below T g , a sudden increase in the crystal growth rate can be observed [ 8 , 9 , 10 ]. GC growth initially generally exhibits a fiber-like form as a precursor, and compact spherulites with further cooling [ 11 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

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Crystallization of Amorphous Nimesulide: The Relationship between Crystal Growth Kinetics and Liquid Dynamics

2023

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Understanding crystallization and its correlations with liquid dynamics is relevant for developing robust amorphous pharmaceutical solids. Herein, nimesulide, a classical anti-inflammatory agent, was used as a model system for studying the correlations between crystallization kinetics and molecular dynamics. Kinetic parts of crystal growth (ukin) of nimesulide exhibited a power law dependence upon the liquid viscosity (η) as ukin~η−0.61. Bulk molecular diffusivities (DBulk) of nimesulide were predicted by a force-level statistical–mechanical model from the α-relaxation times, which revealed the relationship as ukin~Dbulk0.65. Bulk crystal growth kinetics of nimesulide in deeply supercooled liquid exhibited a fragility-dependent decoupling from τα. The correlations between growth kinetics and α-relaxation times predicted by the Adam–Gibbs–Vogel equation in a glassy state were also explored, for both the freshly made and fully equilibrated glass. These findings are relevant for the in-depth understanding and prediction of the physical stability of amorphous pharmaceutical solids.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Crystallization of Amorphous Nimesulide: The Relationship between Crystal Growth Kinetics and Liquid Dynamics

2023

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Section: Introductionmentioning

confidence: 99%

“…Nucleation is also influenced by the liquid/vapor interface. ,− A drug molecule at the free surface is in a special environment compared with those in the interior. ,, Compared to bulk molecules, surface molecules have higher degrees of freedom due to having fewer or different neighbors, thus exhibiting a higher mobility . It has been reported that surface molecules exhibit different molecular orientations compared to bulk molecules . It has been recently reported that the nucleation of molecular liquid was significantly enhanced by surface effects. ,, Yu and co-workers investigated an interesting case of surface-enhanced nucleation of D-arabitol .…”

Section: Introductionmentioning

confidence: 99%

Investigation into Surface Effects on the Crystal Nucleation and Growth of Clotrimazole Polymorphs

Zhang

Xu²,

et al. 2023

Crystal Growth & Design

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Molecules at the surface are spatially different compared to those in the bulk and potentially influence crystallization. In this study, surface effects on crystallization behaviors of two clotrimazole (CMZ) polymorphs were investigated. Form 2 of CMZ is favored to nucleate both at the surface and in the bulk. The nucleation rates of CMZ polymorphs at the surface are vastly accelerated by 5−6.5 orders of magnitude compared to their bulk nucleation rates. The surface-accelerating effect on the nucleation rates for Form 2 is relatively stronger than that for Form 1. The surface molecular structure and surface dynamics exhibit a combined effect on the enhancement of surface nucleation. The surface also enhances growth rates of the two polymorphs while exhibiting a greater accelerating effect on Form 1. The growth rates of Form 2 are higher in the bulk, while they show the opposite order at the surface, with Form 1 growing faster. The classical nucleation theory holds true in the present system both at the surface and in the bulk, and the thermodynamic barriers of the two nucleation processes are similar. This study is relevant for understanding the nucleation and growth kinetics of drug polymorphs at the surface.

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“…Atomic layer coating (ALC) is emerging as a novel strategy to inhibit surface crystallization in amorphous solid dispersions upon storage. , ALC is a solvent free, layer-by-layer technique in which a nanoscale film (<10–100 nm) is applied to the surface of a substrate. − Following application of an aluminum oxide coating of 5–40 nm, high drug loading ASD formulations, which were otherwise found to crystallize in <1 month at highly accelerated open dish storage conditions, were stable for 6 months to over 2 years. , This surface engineering strategy is highly successful because surface crystallization, which is orders of magnitude faster than bulk (interior) crystallization, is inhibited. − In other studies, ALC has shown benefit for other surface-mediated phenomena, such as improved wettability, dispersibility, and powder flowability, as well as reduced agglomeration and hygroscopicity. ,− The impact of ALC on ASD crystallization behavior in solution environments is as of yet largely unexplored.…”

Section: Introductionmentioning

confidence: 99%

Impact of Aluminum Oxide Nanocoating on Drug Release from Amorphous Solid Dispersion Particles

et al. 2022

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Atomic layer coating (ALC) is emerging as a particle engineering strategy to inhibit surface crystallization of amorphous solid dispersions (ASDs). In this study, we turn our attention to evaluating drug release behavior from ALC-coated ASDs, and begin to develop a mechanistic framework. Posaconazole/hydroxypropyl methylcellulose acetate succinate was used as a model system at both 25% and 50% drug loadings. ALC-coatings of aluminum oxide up to 40 nm were evaluated for water sorption kinetics and dissolution performance under a range of pH conditions. Scanning electron microscopy with energy dispersive X-ray analysis was used to investigate the microstructure of partially released ASD particles. Coating thickness and defect density (inferred from deposition rates) were found to impact water sorption kinetics. Despite reduced water sorption kinetics, the presence of a coating was not found to impact dissolution rates under conditions where rapid drug release was observed. Under slower releasing conditions, underlying matrix crystallization was reduced by the coating, enabling greater levels of drug release. These results demonstrate that water was able to penetrate through the ALC coating, hydrating the amorphous solid, which can initiate dissolution of drug and/or polymer (depending on pH conditions). Swelling of the ASD substrate subsequently occurs, disrupting and cracking the coating, which serves to facilitate rapid drug release. Water sorption kinetics are highlighted as a potential predictive tool to investigate the coating quality and its potential impact on dissolution performance. This study has implications for formulation design and evaluation of ALC-coated ASD particles.

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Physical stability and dissolution behaviors of amorphous pharmaceutical solids: Role of surface and interface effects

Cited by 15 publications

References 84 publications

Crystallization of Amorphous Nimesulide: The Relationship between Crystal Growth Kinetics and Liquid Dynamics

Crystallization of Amorphous Nimesulide: The Relationship between Crystal Growth Kinetics and Liquid Dynamics

Investigation into Surface Effects on the Crystal Nucleation and Growth of Clotrimazole Polymorphs

Impact of Aluminum Oxide Nanocoating on Drug Release from Amorphous Solid Dispersion Particles

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