Potential application of low molecular weight excipients for amorphization and dissolution enhancement of carvedilol
Samo za registrovane korisnike
2021
Autori
Pešić, NikolaDapčević, Aleksandra
Ivković, Branka
Kachrimanis, Kyriakos
Mitrić, Miodrag
Ibrić, Svetlana
Medarević, Đorđe
Članak u časopisu (Objavljena verzija)
Metapodaci
Prikaz svih podataka o dokumentuApstrakt
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.
Ključne reči:
Amino acids / Amorphization / Ball milling / Co-amorphous systems / Poorly soluble drugs / SupersaturationIzvor:
International Journal of Pharmaceutics, 2021, 608Izdavač:
- Elsevier B.V.
Finansiranje / projekti:
DOI: 10.1016/j.ijpharm.2021.121033
ISSN: 0378-5173
WoS: 000696904600005
Scopus: 2-s2.0-85114692089
Institucija/grupa
PharmacyTY - JOUR AU - Pešić, Nikola AU - Dapčević, Aleksandra AU - Ivković, Branka AU - Kachrimanis, Kyriakos AU - Mitrić, Miodrag AU - Ibrić, Svetlana AU - Medarević, Đorđe PY - 2021 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3964 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. PB - Elsevier B.V. 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 = "Pešić, Nikola and Dapčević, Aleksandra and Ivković, Branka and Kachrimanis, Kyriakos and Mitrić, Miodrag and Ibrić, Svetlana and Medarević, 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.", publisher = "Elsevier B.V.", 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" }
Pešić, N., Dapčević, A., Ivković, B., Kachrimanis, K., Mitrić, M., Ibrić, S.,& Medarević, Đ.. (2021). Potential application of low molecular weight excipients for amorphization and dissolution enhancement of carvedilol. in International Journal of Pharmaceutics Elsevier B.V.., 608. https://doi.org/10.1016/j.ijpharm.2021.121033
Pešić N, Dapčević A, Ivković B, Kachrimanis K, Mitrić M, Ibrić S, Medarević 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 .
Pešić, Nikola, Dapčević, Aleksandra, Ivković, Branka, Kachrimanis, Kyriakos, Mitrić, Miodrag, Ibrić, Svetlana, Medarević, 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 . .