Unravelling the Miscibility of Poly(2-oxazoline)s: A Novel Polymer Class for the Formulation of Amorphous Solid Dispersions
| Autor: | Richard Hoogenboom, Peter Adriaensens, Victor Retamero De La Rosa, Ali Tigrine, Guy Van den Mooter, Melissa Everaerts, Christian Clasen |
|---|---|
| Přispěvatelé: | Clasen, Christian/0000-0002-9253-9008, Everaerts, Melissa/0000-0003-1376-3181 |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
STABILIZATION
Materials science Carrier system GLASS-TRANSITION TEMPERATURE Drug Compounding Indomethacin Pharmaceutical Science IMMISCIBILITY FILMS BLENDS Miscibility Article Analytical Chemistry lcsh:QD241-441 modulated differential scanning calorimetry Differential scanning calorimetry lcsh:Organic chemistry solid-state nuclear magnetic resonance spectroscopy Drug Discovery Physical and Theoretical Chemistry HOT-MELT EXTRUSION Oxazoles Dissolution Alkyl chemistry.chemical_classification Drug Carriers Precipitation (chemistry) Organic Chemistry poly(2-oxazoline)s Polymer Amorphous solid Chemistry Drug Liberation Solubility Chemical engineering chemistry Chemistry (miscellaneous) miscibility Molecular Medicine amorphous solid dispersions |
| Zdroj: | Molecules Volume 25 Issue 16 Molecules, Vol 25, Iss 3587, p 3587 (2020) MOLECULES |
| ISSN: | 1420-3049 |
| Popis: | Water-soluble polymers are still the most popular carrier for the preparation of amorphous solid dispersions (ASDs). The advantage of this type of carrier is the fast drug release upon dissolution of the water-soluble polymer and thus the initial high degree of supersaturation of the poorly soluble drug. Nevertheless, the risk for precipitation due to fast drug release is a phenomenon that is frequently observed. In this work, we present an alternative carrier system for ASDs where a water-soluble and water-insoluble carrier are combined to delay the drug release and thus prevent this onset of precipitation. Poly(2-alkyl-2-oxazoline)s were selected as a polymer platform since the solution properties of this polymer class depend on the length of the alkyl sidechain. Poly(2-ethyl-2-oxazoline) (PEtOx) behaves as a water-soluble polymer at body temperature, while poly(2-n-propyl-2-oxazoline) (PPrOx) and poly(2-sec-butyl-2-oxazoline) (PsecBuOx) are insoluble at body temperature. Since little was known about the polymer&rsquo s miscibility behaviour and especially on how the presence of a poorly-water soluble drug impacted their miscibility, a preformulation study was performed. Formulations were investigated with X-ray powder diffraction, differential scanning calorimetry (DSC) and solid-state nuclear magnetic resonance spectroscopy. PEtOx/PPrOx appeared to form an immiscible blend based on DSC and this was even more pronounced after heating. The six drugs that were tested in this work did not show any preference for one of the two phases. PEtOx/PsecBuOx on the other hand appeared to be miscible forming a homogeneous blend between the two polymers and the drugs. |
| Databáze: | OpenAIRE |
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