Number of the records: 1
Structural insight into the physical stability of amorphous Simvastatin dispersed in pHPMA: enhanced dynamics and local clustering as evidenced by solid-state NMR and Raman spectroscopy
- 1.
SYSNO ASEP 0439661 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Structural insight into the physical stability of amorphous Simvastatin dispersed in pHPMA: enhanced dynamics and local clustering as evidenced by solid-state NMR and Raman spectroscopy Author(s) Urbanová, Martina (UMCH-V) RID, ORCID
Šturcová, Adriana (UMCH-V) RID
Kredatusová, Jana (UMCH-V) RID
Brus, Jiří (UMCH-V) RID, ORCIDSource Title International Journal of Pharmaceutics. - : Elsevier - ISSN 0378-5173
Roč. 478, č. 2 (2015), s. 464-475Number of pages 12 s. Language eng - English Country GB - United Kingdom Keywords solid dispersions ; simvastatin ; pharmaceuticals Subject RIV CD - Macromolecular Chemistry R&D Projects GA14-03636S GA ČR - Czech Science Foundation (CSF) LD14010 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Institutional support UMCH-V - RVO:61389013 UT WOS 000349723300005 EID SCOPUS 84920849238 DOI 10.1016/j.ijpharm.2014.12.007 Annotation New drug formulations are sought for poorly water-soluble substances because there is a risk of compromised bioavailability if such substances are administered orally. Such active pharmaceutical ingredients can be reformulated as solid dispersions with suitable water-soluble polymers. In this contribution, formulation of a novel and physically stable dispersion of Simvastatin in poly(2-hydroxypropyl) methacrylamide (pHPMA) is demonstrated. Due to the limited water sorption of pHPMA and a high Tg, the prepared dispersion is more suited for oral administration and storage compared with neat amorphous Simvastatin. Surprisingly, the rate of global reorientation and the internal motion of Simvastatin molecules were enhanced and exhibited dynamical heterogeneities when incorporated into the pHPMA matrix. As revealed by solid-state nuclear magnetic resonance combined with Raman spectroscopy exploiting the fluorescence phenomenon the mobility of the ester and lactone components increased considerably, whereas the naphthalene ring remained rigid. Furthermore, the solid dispersion was found to be nano-heterogeneous with nanometer-sized Simvastatin domains. The presence of these clusters had no impact on the dynamics of the rigid pHPMA chains. Thus, the diffusion of Simvastatin molecules through the glassy pHPMA walls and the subsequent transformation of the clusters into larger crystallites were prevented. No crystallization was detected for more than two years. Workplace Institute of Macromolecular Chemistry Contact Eva Čechová, cechova@imc.cas.cz ; Tel.: 296 809 358 Year of Publishing 2015
Number of the records: 1