Potential application of low molecular weight excipients for amorphization and dissolution enhancement of carvedilol
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2021
Authors
Pesic, NikolaDapčević, Aleksandra
Ivkovic, Branka
Kachrimanis, Kyriakos
Mitric, Miodrag
Ibric, Svetlana
Medarevic, Đorđe
Article (Published version)
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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 millingSource:
International Journal of Pharmaceutics, 2021, 608Funding / projects:
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200161 (University of Belgrade, Faculty of Pharmacy) (RS-MESTD-inst-2020-200161)
DOI: 10.1016/j.ijpharm.2021.121033
ISSN: 0378-5173
PubMed: 34419592
WoS: 000696904600005
Scopus: 2-s2.0-85114692089
Institution/Community
Tehnološko-metalurški fakultetTY - 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 . .