Co-milling of glass forming ability class III drugs: Comparing the impact of low and high glass transition temperatures
Jazyk angličtina Země Nizozemsko Médium print-electronic
Typ dokumentu časopisecké články, srovnávací studie
PubMed
40139572
DOI
10.1016/j.ejps.2025.107081
PII: S0928-0987(25)00080-6
Knihovny.cz E-zdroje
- Klíčová slova
- Ball milling, Co-milling, Croscarmellose sodium, Drug supersaturation, Glass forming ability, Glass transition temperature, Melting point depression,
- MeSH
- Aspirin chemie analogy a deriváty MeSH
- fenofibrát * chemie MeSH
- pomocné látky chemie MeSH
- příprava léků metody MeSH
- rozpustnost MeSH
- sklo * chemie MeSH
- tranzitní teplota MeSH
- uvolňování léčiv MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
- Názvy látek
- apremilast MeSH Prohlížeč
- Aspirin MeSH
- fenofibrát * MeSH
- pomocné látky MeSH
- thalidomid MeSH
With an increasing focus on sustainable technologies in the pharmaceutical industry, milling provides a solvent-free approach to improve drug dissolution. Milling of drugs with an excipient offers additional opportunities to achieve supersaturation kinetics. Therefore, this work aims to present insights of co-milling fenofibrate and apremilast, two good glass formers with low and high glass transition temperatures (Tgs) respectively. Drugs were co-milled with croscarmellose sodium for various process durations followed by thermal analysis, investigation of crystallinity, surface area and dissolution. The dissolution enhancement of the low-Tg glass former fenofibrate highly correlated with the process-induced increase in surface area of co-milled systems (R2 = 0.96). In contrast, the high-Tg glass former apremilast lost its crystalline order gradually after ≥ 10 min of co-milling, and favourable supersaturation kinetics during biorelevant dissolution testing were observed. Interestingly, the melting point of co-milled apremilast decreased and linearly correlated with the highest measured drug concentration (cmax) during in vitro dissolution (onset temperature R2 = 0.98; peak temperature R2 = 0.96). The melting point depression remained stable after 90 days for apremilast, whereas fenofibrate co-milled for 20 min or more showed an increase in melting point upon storage. This study demonstrated that co-milling with croscarmellose sodium is ideally suited to good glass formers with a high Tg. The melting point depression is thereby proposed as an easily accessible critical quality attribute to estimate likely dissolution performance of drugs in dry co-milled formulations.
Department Preformulation and Biopharmacy Zentiva k s Prague Czechia
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