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Potential application of low molecular weight excipients for amorphization and dissolution enhancement of carvedilol

Authorized Users Only
2021
Authors
Pesic, Nikola
Dapčević, Aleksandra
Ivkovic, Branka
Kachrimanis, Kyriakos
Mitric, Miodrag
Ibric, Svetlana
Medarevic, Đorđe
Article (Published version)
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Abstract
In this study, four low molecular weight (LMW) excipients, tryptophan (TRY), phenylalanine (PHE), lysine (LYS) and saccharin (SAC) were evaluated as co-formers to generate co-amorphous systems (CAMS) by ball milling with carvedilol (CRV). Mixtures of CRV and LMW excipient in 1:0.5, 1:1 and 1:2 drug:excipient molar ratios were ball milled and analysed by powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), Fourier transform (FT-IR) infrared spectroscopy and dissolution testing. CAMS were formed by milling of a mixture of CRV with TRY in 1:2 M ratio and SAC in 1:1 M ratio, while amorphization of only CRV was achieved in other mixtures with SAC. In other samples containing TRY and PHE, milling resulted in partial amorphization, while LYS was the least suitable excipient for the amorphization of CRV. Unexpectedly, the highest supersaturation of CRV was achieved from samples containing CRV and LYS in 1:1 and 1:2 M ratios, despite the absence of a significant reduction i...n CRV crystallinity upon milling of these samples. Increase of hydrophobic surface area caused by milling of samples with TRY and PHE and agglomeration during dissolution testing of samples containing SAC are likely causes of poor dissolution performance of mixtures containing fully or partially amorphous CRV.

Keywords:
Co-amorphous systems / Poorly soluble drugs / Amino acids / Amorphization / Supersaturation / Ball milling
Source:
International Journal of Pharmaceutics, 2021, 608
Funding / projects:
  • Ministry of Education, Science and Technological Development, Republic of Serbia, Grant no. 200161 (University of Belgrade, Faculty of Pharmacy) (RS-200161)

DOI: 10.1016/j.ijpharm.2021.121033

ISSN: 0378-5173

PubMed: 34419592

WoS: 000696904600005

Scopus: 2-s2.0-85114692089
[ Google Scholar ]
4
1
URI
http://TechnoRep.tmf.bg.ac.rs/handle/123456789/4805
Collections
  • Radovi istraživača / Researchers’ publications (TMF)
Institution/Community
Tehnološko-metalurški fakultet
TY  - JOUR
AU  - Pesic, Nikola
AU  - Dapčević, Aleksandra
AU  - Ivkovic, Branka
AU  - Kachrimanis, Kyriakos
AU  - Mitric, Miodrag
AU  - Ibric, Svetlana
AU  - Medarevic, Đorđe
PY  - 2021
UR  - http://TechnoRep.tmf.bg.ac.rs/handle/123456789/4805
AB  - In this study, four low molecular weight (LMW) excipients, tryptophan (TRY), phenylalanine (PHE), lysine (LYS) and saccharin (SAC) were evaluated as co-formers to generate co-amorphous systems (CAMS) by ball milling with carvedilol (CRV). Mixtures of CRV and LMW excipient in 1:0.5, 1:1 and 1:2 drug:excipient molar ratios were ball milled and analysed by powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), Fourier transform (FT-IR) infrared spectroscopy and dissolution testing. CAMS were formed by milling of a mixture of CRV with TRY in 1:2 M ratio and SAC in 1:1 M ratio, while amorphization of only CRV was achieved in other mixtures with SAC. In other samples containing TRY and PHE, milling resulted in partial amorphization, while LYS was the least suitable excipient for the amorphization of CRV. Unexpectedly, the highest supersaturation of CRV was achieved from samples containing CRV and LYS in 1:1 and 1:2 M ratios, despite the absence of a significant reduction in CRV crystallinity upon milling of these samples. Increase of hydrophobic surface area caused by milling of samples with TRY and PHE and agglomeration during dissolution testing of samples containing SAC are likely causes of poor dissolution performance of mixtures containing fully or partially amorphous CRV.
T2  - International Journal of Pharmaceutics
T1  - Potential application of low molecular weight excipients for amorphization and dissolution enhancement of carvedilol
VL  - 608
DO  - 10.1016/j.ijpharm.2021.121033
ER  - 
@article{
author = "Pesic, Nikola and Dapčević, Aleksandra and Ivkovic, Branka and Kachrimanis, Kyriakos and Mitric, Miodrag and Ibric, Svetlana and Medarevic, Đorđe",
year = "2021",
abstract = "In this study, four low molecular weight (LMW) excipients, tryptophan (TRY), phenylalanine (PHE), lysine (LYS) and saccharin (SAC) were evaluated as co-formers to generate co-amorphous systems (CAMS) by ball milling with carvedilol (CRV). Mixtures of CRV and LMW excipient in 1:0.5, 1:1 and 1:2 drug:excipient molar ratios were ball milled and analysed by powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), Fourier transform (FT-IR) infrared spectroscopy and dissolution testing. CAMS were formed by milling of a mixture of CRV with TRY in 1:2 M ratio and SAC in 1:1 M ratio, while amorphization of only CRV was achieved in other mixtures with SAC. In other samples containing TRY and PHE, milling resulted in partial amorphization, while LYS was the least suitable excipient for the amorphization of CRV. Unexpectedly, the highest supersaturation of CRV was achieved from samples containing CRV and LYS in 1:1 and 1:2 M ratios, despite the absence of a significant reduction in CRV crystallinity upon milling of these samples. Increase of hydrophobic surface area caused by milling of samples with TRY and PHE and agglomeration during dissolution testing of samples containing SAC are likely causes of poor dissolution performance of mixtures containing fully or partially amorphous CRV.",
journal = "International Journal of Pharmaceutics",
title = "Potential application of low molecular weight excipients for amorphization and dissolution enhancement of carvedilol",
volume = "608",
doi = "10.1016/j.ijpharm.2021.121033"
}
Pesic, N., Dapčević, A., Ivkovic, B., Kachrimanis, K., Mitric, M., Ibric, S.,& Medarevic, Đ.. (2021). Potential application of low molecular weight excipients for amorphization and dissolution enhancement of carvedilol. in International Journal of Pharmaceutics, 608.
https://doi.org/10.1016/j.ijpharm.2021.121033
Pesic N, Dapčević A, Ivkovic B, Kachrimanis K, Mitric M, Ibric S, Medarevic Đ. Potential application of low molecular weight excipients for amorphization and dissolution enhancement of carvedilol. in International Journal of Pharmaceutics. 2021;608.
doi:10.1016/j.ijpharm.2021.121033 .
Pesic, Nikola, Dapčević, Aleksandra, Ivkovic, Branka, Kachrimanis, Kyriakos, Mitric, Miodrag, Ibric, Svetlana, Medarevic, Đorđe, "Potential application of low molecular weight excipients for amorphization and dissolution enhancement of carvedilol" in International Journal of Pharmaceutics, 608 (2021),
https://doi.org/10.1016/j.ijpharm.2021.121033 . .

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