Exploring space-energy matching via quantum-molecular mechanics modeling and breakage dynamics-energy dissipation via microhydrodynamic modeling to improve the screening efficiency of nanosuspension prepared by wet media milling

Tian, Jing; Qiao, Fangxia; Hou, Yanhui; Tian, Bin; Yang, Jianhong

doi:10.1080/17425247.2021.1967928

Cited by 2 publications

(2 citation statements)

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“…While nanosuspensions present a promising approach to improve the solubility and dissolution of active pharmaceutical ingredients, choosing the correct formulation to stabilize a chosen drug remains a difficult task. Traditional approaches have focused on more experimental characterization methods, but recent efforts have shown computational modeling may aid in the design of stable nanosuspensions [ 32 , 33 , 34 ]. To continue in this direction, we applied molecular dynamics simulations to quantify drug–excipient interactions and find underlying physical characteristics that can predict nanosuspension stability.…”

Section: Resultsmentioning

confidence: 99%

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Utilizing Molecular Simulations to Examine Nanosuspension Stability

Latham,

Levy,

Sellers

et al. 2023

Pharmaceutics

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Drug nanosuspensions offer a promising approach to improve bioavailability for poorly soluble drug candidates. Such formulations often necessitate the inclusion of an excipient to stabilize the drug nanoparticles. However, the rationale for the choice of the correct excipient for a given drug candidate remains unclear. To gain molecular insight into formulation design, this work first utilizes a molecular dynamics simulation to computationally investigate drug–excipient interactions for a number of combinations that have been previously studied experimentally. We find that hydrophobic interactions drive excipient adsorption to drug nanoparticles and that the fraction of polar surface area serves as a predictor for experimental measurements of nanosuspension stability. To test these ideas prospectively, we applied our model to an uncharacterized drug compound, GDC-0810. Our simulations predicted that a salt form of GDC-0810 would lead to more stable nanosuspensions than the neutral form; therefore, we tested the stability of salt GDC-0810 nanosuspensions and found that the salt form readily formed nanosuspensions even without the excipient. To avoid computationally expensive simulations in the future, we extended our model by showing that simple, two-dimensional properties of single drug molecules can be used to rationalize nanosuspension designs without simulations. In all, our work demonstrates how computational tools can provide molecular insight into drug–excipient interactions and aid in rational formulation design.

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Section: Resultsmentioning

confidence: 99%

“…Computational modeling offers a promising approach for examining the interactions that dictate nanosuspension stability [ 32 , 33 , 34 ]. Electronic structure methods such as density functional theory can be used to most accurately evaluate drug–nanoparticle interactions [ 35 , 36 ].…”

Section: Introductionmentioning

confidence: 99%

Utilizing Molecular Simulations to Examine Nanosuspension Stability

Latham,

Levy,

Sellers

et al. 2023

Pharmaceutics

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Leveraging Numerical Simulation Technology to Advance Drug Preparation: A Comprehensive Review of Application Scenarios and Cases

Gu,

Wu,

Sui

et al. 2024

Pharmaceutics

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Background/Objectives: Numerical simulation plays an important role in pharmaceutical preparation recently. Mechanistic models, as a type of numerical model, are widely used in the study of pharmaceutical preparations. Mechanistic models are based on a priori knowledge, i.e., laws of physics, chemistry, and biology. However, due to interdisciplinary reasons, pharmacy researchers have greater difficulties in using computer models. Methods: In this paper, we highlight the application scenarios and examples of mechanistic modelling in pharmacy research and provide a reference for drug researchers to get started. Results: By establishing a suitable model and inputting preparation parameters, researchers can analyze the drug preparation process. Therefore, mechanistic models are effective tools to optimize the preparation parameters and predict potential quality problems of the product. With product quality parameters as the ultimate goal, the experiment design is optimized by mechanistic models. This process emphasizes the concept of quality by design. Conclusions: The use of numerical simulation saves experimental cost and time, and speeds up the experimental process. In pharmacy experiments, part of the physical information and the change processes are difficult to obtain, such as the mechanical phenomena during tablet compression and the airflow details in the nasal cavity. Therefore, it is necessary to predict the information and guide the formulation with the help of mechanistic models.

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Exploring space-energy matching via quantum-molecular mechanics modeling and breakage dynamics-energy dissipation via microhydrodynamic modeling to improve the screening efficiency of nanosuspension prepared by wet media milling

Cited by 2 publications

References 91 publications

Utilizing Molecular Simulations to Examine Nanosuspension Stability

Utilizing Molecular Simulations to Examine Nanosuspension Stability

Leveraging Numerical Simulation Technology to Advance Drug Preparation: A Comprehensive Review of Application Scenarios and Cases

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