Journal
JOURNAL OF MOLECULAR LIQUIDS
Volume 222, Issue -, Pages 287-294Publisher
ELSEVIER
DOI: 10.1016/j.molliq.2016.07.025
Keywords
Poly(vinyl alcohol); Simvastatin; Hydrophobic interactions; Solubilization; Release kinetics
Funding
- Coimbra Chemistry Centre (CQC)
- Fundacao para a Ciencia e a Tecnologia (FCT)
- Portuguese Agency for Scientific Research [UID/QUI/UI0313/2013]
- COMPETE Programme (Operational Programme for Competitiveness)
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Simvastatin (SV) is a common drug, used for reducing LDL-C levels in blood. One of its drawbacks is poor solubility in water. This forces the use of large therapeutic doses, which enhances side effects. Poly(vinyl alcohol) (PVA) hydrogels have most of the desirable properties required as a matrix for dissolution and delivery of SV. The interaction between SV and PVA, in cryogel matrices, that leads to the enhancement of SV solubility was studied. From thermal analysis, it was found that upon increasing the amount of SV incorporated into PVA matrices, the degradation temperature of PVA decreases. This decrease is accompanied by a decrease in the melting temperature and in the corresponding melting enthalpy, as seen by differential scanning calorimetry (DSC), indicating that in the presence of SV, the PVA structure becomes more amorphous. Molecular dynamics (MD) studies show that the structure of PVA in water suffers changes in the presence of SV, such that the hydroxyl groups tend to move away from SV, allowing for a better interaction of the latter with the hydrocarbon chain, whilst hydroxyl groups interact with water molecules, suggesting an amphiphilic behavior of PVA. The interaction between SV and PVA is also confirmed by release kinetics to water-ethanol (1:1 v/v) and water. In conclusion, this brings new promising opportunities for using this polymer as a prolonged-release cryogel matrix suitable both for the entrapment and release of moderately or highly hydrophobic drugs into water. (C) 2016 Elsevier B.V. All rights reserved.
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