An emerging terpolymeric nanoparticle pore former as an internal recrystallization inhibitor of celecoxib in controlled release amorphous solid dispersion beads: Experimental studies and molecular dynamics analysis

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Standard

An emerging terpolymeric nanoparticle pore former as an internal recrystallization inhibitor of celecoxib in controlled release amorphous solid dispersion beads : Experimental studies and molecular dynamics analysis. / Lugtu-Pe, Jamie Anne; Zhang, Xuning; Mirzaie, Sako; Chang, Hao Han R.; AL-Mousawi, Nour; Chen, Kuan; Li, Yongqiang; Kane, Anil; Bar-Shalom, Daniel; Wu, Xiao Yu.

I: Acta Pharmaceutica Sinica B, Bind 14, Nr. 6, 2024, s. 2669-2684.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Harvard

Lugtu-Pe, JA, Zhang, X, Mirzaie, S, Chang, HHR, AL-Mousawi, N, Chen, K, Li, Y, Kane, A, Bar-Shalom, D & Wu, XY 2024, 'An emerging terpolymeric nanoparticle pore former as an internal recrystallization inhibitor of celecoxib in controlled release amorphous solid dispersion beads: Experimental studies and molecular dynamics analysis', Acta Pharmaceutica Sinica B, bind 14, nr. 6, s. 2669-2684. https://doi.org/10.1016/j.apsb.2024.03.026

APA

Lugtu-Pe, J. A., Zhang, X., Mirzaie, S., Chang, H. H. R., AL-Mousawi, N., Chen, K., Li, Y., Kane, A., Bar-Shalom, D., & Wu, X. Y. (2024). An emerging terpolymeric nanoparticle pore former as an internal recrystallization inhibitor of celecoxib in controlled release amorphous solid dispersion beads: Experimental studies and molecular dynamics analysis. Acta Pharmaceutica Sinica B, 14(6), 2669-2684. https://doi.org/10.1016/j.apsb.2024.03.026

Vancouver

Lugtu-Pe JA, Zhang X, Mirzaie S, Chang HHR, AL-Mousawi N, Chen K o.a. An emerging terpolymeric nanoparticle pore former as an internal recrystallization inhibitor of celecoxib in controlled release amorphous solid dispersion beads: Experimental studies and molecular dynamics analysis. Acta Pharmaceutica Sinica B. 2024;14(6):2669-2684. https://doi.org/10.1016/j.apsb.2024.03.026

Author

Lugtu-Pe, Jamie Anne ; Zhang, Xuning ; Mirzaie, Sako ; Chang, Hao Han R. ; AL-Mousawi, Nour ; Chen, Kuan ; Li, Yongqiang ; Kane, Anil ; Bar-Shalom, Daniel ; Wu, Xiao Yu. / An emerging terpolymeric nanoparticle pore former as an internal recrystallization inhibitor of celecoxib in controlled release amorphous solid dispersion beads : Experimental studies and molecular dynamics analysis. I: Acta Pharmaceutica Sinica B. 2024 ; Bind 14, Nr. 6. s. 2669-2684.

Bibtex

@article{d27432b450674c69abf0d48b5515d3c0,
title = "An emerging terpolymeric nanoparticle pore former as an internal recrystallization inhibitor of celecoxib in controlled release amorphous solid dispersion beads: Experimental studies and molecular dynamics analysis",
abstract = "Solid oral controlled release formulations feature numerous clinical advantages for drug candidates with adequate solubility and dissolution rate. However, most new chemical entities exhibit poor water solubility, and hence are exempt from such benefits. Although combining drug amorphization with controlled release formulation is promising to elevate drug solubility, like other supersaturating systems, the problem of drug recrystallization has yet to be resolved, particularly within the dosage form. Here, we explored the potential of an emerging, non-leachable terpolymer nanoparticle (TPN) pore former as an internal recrystallization inhibitor within controlled release amorphous solid dispersion (CRASD) beads comprising a poorly soluble drug (celecoxib) reservoir and insoluble polymer (ethylcellulose) membrane. Compared to conventional pore former, polyvinylpyrrolidone (PVP), TPN-containing membranes exhibited superior structural integrity, less crystal formation at the CRASD bead surface, and greater extent of celecoxib release. All-atom molecular dynamics analyses revealed that in the presence of TPN, intra-molecular bonding, crystal formation tendency, diffusion coefficient, and molecular flexibility of celecoxib were reduced, while intermolecular H-bonding was increased as compared to PVP. This work suggests that selection of a pore former that promotes prolonged molecular separation within a nanoporous controlled release membrane structure may serve as an effective strategy to enhance amorphicity preservation inside CRASD.",
keywords = "Controlled release amorphous solid dispersion, Drug-polymer interactions, Effect of pore formers, Internal recrystallization, Membrane-reservoir coated beads, Molecular dynamics simulation, Poorly soluble drug, Terpolymer nanogel",
author = "Lugtu-Pe, {Jamie Anne} and Xuning Zhang and Sako Mirzaie and Chang, {Hao Han R.} and Nour AL-Mousawi and Kuan Chen and Yongqiang Li and Anil Kane and Daniel Bar-Shalom and Wu, {Xiao Yu}",
note = "Publisher Copyright: {\textcopyright} 2024 The Authors",
year = "2024",
doi = "10.1016/j.apsb.2024.03.026",
language = "English",
volume = "14",
pages = "2669--2684",
journal = "Acta Pharmaceutica Sinica B (Online)",
issn = "2211-3843",
publisher = "Elsevier",
number = "6",

}

RIS

TY - JOUR

T1 - An emerging terpolymeric nanoparticle pore former as an internal recrystallization inhibitor of celecoxib in controlled release amorphous solid dispersion beads

T2 - Experimental studies and molecular dynamics analysis

AU - Lugtu-Pe, Jamie Anne

AU - Zhang, Xuning

AU - Mirzaie, Sako

AU - Chang, Hao Han R.

AU - AL-Mousawi, Nour

AU - Chen, Kuan

AU - Li, Yongqiang

AU - Kane, Anil

AU - Bar-Shalom, Daniel

AU - Wu, Xiao Yu

N1 - Publisher Copyright: © 2024 The Authors

PY - 2024

Y1 - 2024

N2 - Solid oral controlled release formulations feature numerous clinical advantages for drug candidates with adequate solubility and dissolution rate. However, most new chemical entities exhibit poor water solubility, and hence are exempt from such benefits. Although combining drug amorphization with controlled release formulation is promising to elevate drug solubility, like other supersaturating systems, the problem of drug recrystallization has yet to be resolved, particularly within the dosage form. Here, we explored the potential of an emerging, non-leachable terpolymer nanoparticle (TPN) pore former as an internal recrystallization inhibitor within controlled release amorphous solid dispersion (CRASD) beads comprising a poorly soluble drug (celecoxib) reservoir and insoluble polymer (ethylcellulose) membrane. Compared to conventional pore former, polyvinylpyrrolidone (PVP), TPN-containing membranes exhibited superior structural integrity, less crystal formation at the CRASD bead surface, and greater extent of celecoxib release. All-atom molecular dynamics analyses revealed that in the presence of TPN, intra-molecular bonding, crystal formation tendency, diffusion coefficient, and molecular flexibility of celecoxib were reduced, while intermolecular H-bonding was increased as compared to PVP. This work suggests that selection of a pore former that promotes prolonged molecular separation within a nanoporous controlled release membrane structure may serve as an effective strategy to enhance amorphicity preservation inside CRASD.

AB - Solid oral controlled release formulations feature numerous clinical advantages for drug candidates with adequate solubility and dissolution rate. However, most new chemical entities exhibit poor water solubility, and hence are exempt from such benefits. Although combining drug amorphization with controlled release formulation is promising to elevate drug solubility, like other supersaturating systems, the problem of drug recrystallization has yet to be resolved, particularly within the dosage form. Here, we explored the potential of an emerging, non-leachable terpolymer nanoparticle (TPN) pore former as an internal recrystallization inhibitor within controlled release amorphous solid dispersion (CRASD) beads comprising a poorly soluble drug (celecoxib) reservoir and insoluble polymer (ethylcellulose) membrane. Compared to conventional pore former, polyvinylpyrrolidone (PVP), TPN-containing membranes exhibited superior structural integrity, less crystal formation at the CRASD bead surface, and greater extent of celecoxib release. All-atom molecular dynamics analyses revealed that in the presence of TPN, intra-molecular bonding, crystal formation tendency, diffusion coefficient, and molecular flexibility of celecoxib were reduced, while intermolecular H-bonding was increased as compared to PVP. This work suggests that selection of a pore former that promotes prolonged molecular separation within a nanoporous controlled release membrane structure may serve as an effective strategy to enhance amorphicity preservation inside CRASD.

KW - Controlled release amorphous solid dispersion

KW - Drug-polymer interactions

KW - Effect of pore formers

KW - Internal recrystallization

KW - Membrane-reservoir coated beads

KW - Molecular dynamics simulation

KW - Poorly soluble drug

KW - Terpolymer nanogel

U2 - 10.1016/j.apsb.2024.03.026

DO - 10.1016/j.apsb.2024.03.026

M3 - Journal article

AN - SCOPUS:85190145298

VL - 14

SP - 2669

EP - 2684

JO - Acta Pharmaceutica Sinica B (Online)

JF - Acta Pharmaceutica Sinica B (Online)

SN - 2211-3843

IS - 6

ER -

ID: 390356542