Mechanistic Investigation into Crystallization of Hydrated Co-Amorphous Systems of Flurbiprofen and Lidocaine
<b>Background:</b> It is generally accepted that water as a plasticizer can decrease the glass transition temperatures (T<sub>g</sub>s) of amorphous drugs and drug delivery systems, resulting in physical instabilities. However, a recent study has reported an anti-plasticizing...
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| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-01-01
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| Series: | Pharmaceutics |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1999-4923/17/2/175 |
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| Summary: | <b>Background:</b> It is generally accepted that water as a plasticizer can decrease the glass transition temperatures (T<sub>g</sub>s) of amorphous drugs and drug delivery systems, resulting in physical instabilities. However, a recent study has reported an anti-plasticizing effect of water on amorphous lidocaine (LID). In co-amorphous systems, LID might be used as a co-former to impair the plasticizing effect of water. <b>Method:</b> Flurbiprofen (FLB) was used to form a co-amorphous system with a mole fraction of LID of 0.8. The effect of water on the stability of co-amorphous FLB-LID upon hydration was investigated. The crystallization behaviors of anhydrous and hydrated co-amorphous FLB-LID systems were measured by an isothermal modulated differential scanning calorimetric (iMDSC) method. The relaxation times of the co-amorphous FLB-LID system upon hydration were measured by a broadband dielectric spectroscopy (BDS), and the differences in Gibbs free energy (ΔG) and entropy (ΔS) between the amorphous and crystalline phases were determined by differential scanning calorimetry (DSC). <b>Results:</b> It was found that the crystallization tendency of co-amorphous FLB-LID decreased with the addition of water. Molecular mobility and thermodynamic factors were both investigated to explain the difference in crystallization tendencies of co-amorphous FLB-LID upon hydration. <b>Conclusions:</b> The results of the study showed that LID could be used as an effective co-former to decrease the crystallization tendency of co-amorphous FLB-LID upon hydration by enhancing the entropic (ΔS) and thermodynamic activation barriers (TΔS)<sup>3</sup>/ΔG<sup>2</sup>) to crystallization. |
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| ISSN: | 1999-4923 |