Investigation on Formulation Strategies to Mitigate Compression-Induced Destabilization in Supersaturated Celecoxib Amorphous Solid Dispersions

Research output: Contribution to journalJournal articlepeer-review

Standard

Investigation on Formulation Strategies to Mitigate Compression-Induced Destabilization in Supersaturated Celecoxib Amorphous Solid Dispersions. / Be̅rziņš, Ka̅rlis; Fraser-Miller, Sara J.; Walker, Greg F.; Rades, Thomas; Gordon, Keith C.

In: Molecular Pharmaceutics, Vol. 18, No. 10, 2021, p. 3882–3893.

Research output: Contribution to journalJournal articlepeer-review

Harvard

Be̅rziņš, K, Fraser-Miller, SJ, Walker, GF, Rades, T & Gordon, KC 2021, 'Investigation on Formulation Strategies to Mitigate Compression-Induced Destabilization in Supersaturated Celecoxib Amorphous Solid Dispersions', Molecular Pharmaceutics, vol. 18, no. 10, pp. 3882–3893. https://doi.org/10.1021/acs.molpharmaceut.1c00540

APA

Be̅rziņš, K., Fraser-Miller, S. J., Walker, G. F., Rades, T., & Gordon, K. C. (2021). Investigation on Formulation Strategies to Mitigate Compression-Induced Destabilization in Supersaturated Celecoxib Amorphous Solid Dispersions. Molecular Pharmaceutics, 18(10), 3882–3893. https://doi.org/10.1021/acs.molpharmaceut.1c00540

Vancouver

Be̅rziņš K, Fraser-Miller SJ, Walker GF, Rades T, Gordon KC. Investigation on Formulation Strategies to Mitigate Compression-Induced Destabilization in Supersaturated Celecoxib Amorphous Solid Dispersions. Molecular Pharmaceutics. 2021;18(10):3882–3893. https://doi.org/10.1021/acs.molpharmaceut.1c00540

Author

Be̅rziņš, Ka̅rlis ; Fraser-Miller, Sara J. ; Walker, Greg F. ; Rades, Thomas ; Gordon, Keith C. / Investigation on Formulation Strategies to Mitigate Compression-Induced Destabilization in Supersaturated Celecoxib Amorphous Solid Dispersions. In: Molecular Pharmaceutics. 2021 ; Vol. 18, No. 10. pp. 3882–3893.

Bibtex

@article{f35dc85568f74bc48c1456a13796521b,
title = "Investigation on Formulation Strategies to Mitigate Compression-Induced Destabilization in Supersaturated Celecoxib Amorphous Solid Dispersions",
abstract = "Compression-induced destabilization was investigated in various celecoxib amorphous solid dispersions containing hydroxypropyl methylcellulose (HPMC), poly(vinylpyrrolidone)/vinyl acetate copolymer (PVP/VA), or poly(vinylpyrrolidone) (PVP) at a concentration range of 1-10% w/w. Pharmaceutically relevant (125 MPa pressure with a minimal dwell time) and extreme (500 MPa pressure with a 60 s dwell time) compression conditions were applied to these systems, and the changes in their physical stability were monitored retrospectively (i.e., in the supercooled state) using dynamic differential scanning calorimetry (DSC) and low-frequency Raman (LFR) measurements over a broad temperature range (-90 to 200 and -150 to 140 °C, respectively). Both techniques revealed similar changes in the crystallization behavior between samples, where the application of a higher compression force of 500 MPa resulted in a more pronounced destabilization effect that was progressively mitigated with increasing polymer content. However, other aspects such as more favorable intermolecular interactions did not appear to have any effect on reducing this undesirable effect. Additionally, for the first time, LFR spectroscopy was used as a viable technique to determine the secondary or local glass-transition temperature, Tg,β, a major indicator of the physical stability of neat amorphous pharmaceutical systems. ",
keywords = "amorphous drugs, celecoxib, compression-induced destabilization, differential scanning calorimetry, hydroxypropyl methylcellulose, low-frequency Raman spectroscopy, poly(vinylpyrrolidone), poly(vinylpyrrolidone)/vinyl acetate copolymer",
author = "Ka̅rlis Be̅rziņ{\v s} and Fraser-Miller, {Sara J.} and Walker, {Greg F.} and Thomas Rades and Gordon, {Keith C.}",
note = "Funding Information: K.B. thanks the University of Otago for Ph.D. scholarship. The authors gratefully acknowledge the support from the Dodd-Walls Centre for Photonic and Quantum Technologies. ",
year = "2021",
doi = "10.1021/acs.molpharmaceut.1c00540",
language = "English",
volume = "18",
pages = "3882–3893",
journal = "Molecular Pharmaceutics",
issn = "1543-8384",
publisher = "American Chemical Society",
number = "10",

}

RIS

TY - JOUR

T1 - Investigation on Formulation Strategies to Mitigate Compression-Induced Destabilization in Supersaturated Celecoxib Amorphous Solid Dispersions

AU - Be̅rziņš, Ka̅rlis

AU - Fraser-Miller, Sara J.

AU - Walker, Greg F.

AU - Rades, Thomas

AU - Gordon, Keith C.

N1 - Funding Information: K.B. thanks the University of Otago for Ph.D. scholarship. The authors gratefully acknowledge the support from the Dodd-Walls Centre for Photonic and Quantum Technologies.

PY - 2021

Y1 - 2021

N2 - Compression-induced destabilization was investigated in various celecoxib amorphous solid dispersions containing hydroxypropyl methylcellulose (HPMC), poly(vinylpyrrolidone)/vinyl acetate copolymer (PVP/VA), or poly(vinylpyrrolidone) (PVP) at a concentration range of 1-10% w/w. Pharmaceutically relevant (125 MPa pressure with a minimal dwell time) and extreme (500 MPa pressure with a 60 s dwell time) compression conditions were applied to these systems, and the changes in their physical stability were monitored retrospectively (i.e., in the supercooled state) using dynamic differential scanning calorimetry (DSC) and low-frequency Raman (LFR) measurements over a broad temperature range (-90 to 200 and -150 to 140 °C, respectively). Both techniques revealed similar changes in the crystallization behavior between samples, where the application of a higher compression force of 500 MPa resulted in a more pronounced destabilization effect that was progressively mitigated with increasing polymer content. However, other aspects such as more favorable intermolecular interactions did not appear to have any effect on reducing this undesirable effect. Additionally, for the first time, LFR spectroscopy was used as a viable technique to determine the secondary or local glass-transition temperature, Tg,β, a major indicator of the physical stability of neat amorphous pharmaceutical systems.

AB - Compression-induced destabilization was investigated in various celecoxib amorphous solid dispersions containing hydroxypropyl methylcellulose (HPMC), poly(vinylpyrrolidone)/vinyl acetate copolymer (PVP/VA), or poly(vinylpyrrolidone) (PVP) at a concentration range of 1-10% w/w. Pharmaceutically relevant (125 MPa pressure with a minimal dwell time) and extreme (500 MPa pressure with a 60 s dwell time) compression conditions were applied to these systems, and the changes in their physical stability were monitored retrospectively (i.e., in the supercooled state) using dynamic differential scanning calorimetry (DSC) and low-frequency Raman (LFR) measurements over a broad temperature range (-90 to 200 and -150 to 140 °C, respectively). Both techniques revealed similar changes in the crystallization behavior between samples, where the application of a higher compression force of 500 MPa resulted in a more pronounced destabilization effect that was progressively mitigated with increasing polymer content. However, other aspects such as more favorable intermolecular interactions did not appear to have any effect on reducing this undesirable effect. Additionally, for the first time, LFR spectroscopy was used as a viable technique to determine the secondary or local glass-transition temperature, Tg,β, a major indicator of the physical stability of neat amorphous pharmaceutical systems.

KW - amorphous drugs

KW - celecoxib

KW - compression-induced destabilization

KW - differential scanning calorimetry

KW - hydroxypropyl methylcellulose

KW - low-frequency Raman spectroscopy

KW - poly(vinylpyrrolidone)

KW - poly(vinylpyrrolidone)/vinyl acetate copolymer

U2 - 10.1021/acs.molpharmaceut.1c00540

DO - 10.1021/acs.molpharmaceut.1c00540

M3 - Journal article

C2 - 34529437

AN - SCOPUS:85116158377

VL - 18

SP - 3882

EP - 3893

JO - Molecular Pharmaceutics

JF - Molecular Pharmaceutics

SN - 1543-8384

IS - 10

ER -

ID: 282192816