Integrating Elastic Tensor and PC-SAFT Modeling with Systems-Based Pharma 4.0 Simulation, to Predict Process Operations and Product Specifications of Ternary Nanocrystalline Suspensions

Comminution of BCS II APIs below the 1 μm threshold followed by solidification of the obtained nanosuspensions improves their dissolution properties. The breakage process reveals new crystal faces, thus creating altered crystal habits of improved wettability, facilitated by the adsorption of stabili...

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Autores principales:	Andreas Ouranidis, Christina Davidopoulou, Kyriakos Kachrimanis
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	nanosuspensions elastic tensor analysis process and material design space PC-SAFT spray drying stabilizer selection Pharmacy and materia medica RS1-441
Acceso en línea:	https://doaj.org/article/6e05516f72394f9bb7bdfede5d9e52f5
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spelling	oai:doaj.org-article:6e05516f72394f9bb7bdfede5d9e52f52021-11-25T18:40:33ZIntegrating Elastic Tensor and PC-SAFT Modeling with Systems-Based Pharma 4.0 Simulation, to Predict Process Operations and Product Specifications of Ternary Nanocrystalline Suspensions10.3390/pharmaceutics131117711999-4923https://doaj.org/article/6e05516f72394f9bb7bdfede5d9e52f52021-10-01T00:00:00Zhttps://www.mdpi.com/1999-4923/13/11/1771https://doaj.org/toc/1999-4923Comminution of BCS II APIs below the 1 μm threshold followed by solidification of the obtained nanosuspensions improves their dissolution properties. The breakage process reveals new crystal faces, thus creating altered crystal habits of improved wettability, facilitated by the adsorption of stabilizing polymers. However, process-induced transformations remain unpredictable, mirroring the current limitations of our atomistic level of understanding. Moreover, conventional equations of estimating dissolution, such as Noyes–Whitney and Nernst–Brunner, are not suitable to quantify the solubility enhancement due to the nanoparticle formation; hence, neither the complex stabilizer contribution nor the adsorption influence on the interfacial tension occurring between the water and APIs is accounted for. For such ternary mixtures, no numeric method exists to correlate the mechanical properties with the interfacial energy, capable of informing the key process parameters and the thermodynamic stability assessment of nanosuspensions. In this work, an elastic tensor analysis was performed to quantify the API stability during process implementation. Moreover, a novel thermodynamic model, described by the stabilizer-coated nanoparticle Gibbs energy anisotropic minimization, was structured to predict the material’s system solubility quantified by the application of PC-SAFT modeling. Comprehensively merging elastic tensor and PC-SAFT analysis into the systems-based Pharma 4.0 algorithm provided a validated, multi-level, built-in method capable of predicting the critical material quality attributes and corresponding key process parameters.Andreas OuranidisChristina DavidopoulouKyriakos KachrimanisMDPI AGarticlenanosuspensionselastic tensor analysisprocess and material design spacePC-SAFTspray dryingstabilizer selectionPharmacy and materia medicaRS1-441ENPharmaceutics, Vol 13, Iss 1771, p 1771 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	nanosuspensions elastic tensor analysis process and material design space PC-SAFT spray drying stabilizer selection Pharmacy and materia medica RS1-441
spellingShingle	nanosuspensions elastic tensor analysis process and material design space PC-SAFT spray drying stabilizer selection Pharmacy and materia medica RS1-441 Andreas Ouranidis Christina Davidopoulou Kyriakos Kachrimanis Integrating Elastic Tensor and PC-SAFT Modeling with Systems-Based Pharma 4.0 Simulation, to Predict Process Operations and Product Specifications of Ternary Nanocrystalline Suspensions
description	Comminution of BCS II APIs below the 1 μm threshold followed by solidification of the obtained nanosuspensions improves their dissolution properties. The breakage process reveals new crystal faces, thus creating altered crystal habits of improved wettability, facilitated by the adsorption of stabilizing polymers. However, process-induced transformations remain unpredictable, mirroring the current limitations of our atomistic level of understanding. Moreover, conventional equations of estimating dissolution, such as Noyes–Whitney and Nernst–Brunner, are not suitable to quantify the solubility enhancement due to the nanoparticle formation; hence, neither the complex stabilizer contribution nor the adsorption influence on the interfacial tension occurring between the water and APIs is accounted for. For such ternary mixtures, no numeric method exists to correlate the mechanical properties with the interfacial energy, capable of informing the key process parameters and the thermodynamic stability assessment of nanosuspensions. In this work, an elastic tensor analysis was performed to quantify the API stability during process implementation. Moreover, a novel thermodynamic model, described by the stabilizer-coated nanoparticle Gibbs energy anisotropic minimization, was structured to predict the material’s system solubility quantified by the application of PC-SAFT modeling. Comprehensively merging elastic tensor and PC-SAFT analysis into the systems-based Pharma 4.0 algorithm provided a validated, multi-level, built-in method capable of predicting the critical material quality attributes and corresponding key process parameters.
format	article
author	Andreas Ouranidis Christina Davidopoulou Kyriakos Kachrimanis
author_facet	Andreas Ouranidis Christina Davidopoulou Kyriakos Kachrimanis
author_sort	Andreas Ouranidis
title	Integrating Elastic Tensor and PC-SAFT Modeling with Systems-Based Pharma 4.0 Simulation, to Predict Process Operations and Product Specifications of Ternary Nanocrystalline Suspensions
title_short	Integrating Elastic Tensor and PC-SAFT Modeling with Systems-Based Pharma 4.0 Simulation, to Predict Process Operations and Product Specifications of Ternary Nanocrystalline Suspensions
title_full	Integrating Elastic Tensor and PC-SAFT Modeling with Systems-Based Pharma 4.0 Simulation, to Predict Process Operations and Product Specifications of Ternary Nanocrystalline Suspensions
title_fullStr	Integrating Elastic Tensor and PC-SAFT Modeling with Systems-Based Pharma 4.0 Simulation, to Predict Process Operations and Product Specifications of Ternary Nanocrystalline Suspensions
title_full_unstemmed	Integrating Elastic Tensor and PC-SAFT Modeling with Systems-Based Pharma 4.0 Simulation, to Predict Process Operations and Product Specifications of Ternary Nanocrystalline Suspensions
title_sort	integrating elastic tensor and pc-saft modeling with systems-based pharma 4.0 simulation, to predict process operations and product specifications of ternary nanocrystalline suspensions
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/6e05516f72394f9bb7bdfede5d9e52f5
work_keys_str_mv	AT andreasouranidis integratingelastictensorandpcsaftmodelingwithsystemsbasedpharma40simulationtopredictprocessoperationsandproductspecificationsofternarynanocrystallinesuspensions AT christinadavidopoulou integratingelastictensorandpcsaftmodelingwithsystemsbasedpharma40simulationtopredictprocessoperationsandproductspecificationsofternarynanocrystallinesuspensions AT kyriakoskachrimanis integratingelastictensorandpcsaftmodelingwithsystemsbasedpharma40simulationtopredictprocessoperationsandproductspecificationsofternarynanocrystallinesuspensions
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Integrating Elastic Tensor and PC-SAFT Modeling with Systems-Based Pharma 4.0 Simulation, to Predict Process Operations and Product Specifications of Ternary Nanocrystalline Suspensions

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