Ma, C.Y. orcid.org/0000-0002-4576-7411, Nguyen, T.T.H. orcid.org/0000-0002-6752-1455, Gajjar, P. orcid.org/0000-0001-7109-708X et al. (5 more authors) (2023) Predicting the Strength of Cohesive and Adhesive Interparticle Interactions for Dry Powder Inhalation Blends of Terbutaline Sulfate with α-Lactose Monohydrate. Molecular Pharmaceutics, 20 (10). pp. 5019-5031. ISSN 1543-8384
Abstract
Grid-based systematic search methods are used to investigate molecule–molecule, molecule–surface, and surface–surface contributions to interparticle interactions in order to identify the crystal faces that most strongly affect particle behavior during powder blend formulation and delivery processes. The model system comprises terbutaline sulfate (TBS) as an active pharmaceutical ingredient (API) and α-form lactose monohydrate (LMH). A combination of systematic molecular modeling and X-ray computed tomography (XCT) is used to determine not only the adhesive and cohesive interparticle energies but, also the agglomeration behavior during manufacturing and de-agglomeration behavior during delivery after inhalation. This is achieved through a detailed examination of the balance between the adhesive and cohesive energies with the XCT results confirming the blend segregation tendencies, through the particle–particle de-agglomeration process. The results reveal that the cohesive interaction energies of TBS–TBS are higher than the adhesive energies between TBS and LMH, but that the cohesive energies of LMH–LMH are the smallest between molecule and molecule, molecule and surface, and surface and surface. This shows how systematic grid-search molecular modeling along with XCT can guide the digital formulation design of inhalation powders in order to achieve optimum aerosolization and efficacy for inhaled medicines. This will lead to faster pharmaceutical design with less variability, higher quality, and enhanced performance.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2023 The Authors. This is an open access article under the terms of the Creative Commons Attribution License (CC-BY 4.0), which permits unrestricted use, distribution and reproduction in any medium, provided the original work is properly cited. |
Keywords: | interparticle interactions, molecular modeling, terbutaline sulfate, α-lactose monohydrate, powder inhalation formulations, X-ray computed tomography |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Engineering & Physical Sciences (Leeds) > School of Chemical & Process Engineering (Leeds) The University of Leeds > Faculty of Engineering & Physical Sciences (Leeds) > School of Computing (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 27 Sep 2023 09:46 |
Last Modified: | 27 Oct 2023 15:43 |
Status: | Published |
Publisher: | American Chemical Society |
Identification Number: | 10.1021/acs.molpharmaceut.3c00292 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:203721 |