Papageorgiou G Z, Papadimitriou S, Karavas E, Georgarakis E, Docoslis A, Bikiaris D
Laboratory of Organic Chemical Technology, Chemistry Department, Aristotle University of Thessaloniki, 541 24 Thessaloniki, Greece.
Curr Drug Deliv. 2009 Jan;6(1):101-12. doi: 10.2174/156720109787048230.
Solid dispersions of Fluvastatin with polyvinylpyrrolidone (PVP), eudragit RS100 (Eud), and chitosan (CS) as drug carrier matrices, were prepared using different techniques in order to evaluate their effect on Fluvastatin stability during storage. The characterization of the three different systems was performed with the use of differential scanning calorimetry (DSC) and wide angle X-ray diffractometry (WAXD). It was revealed that amorphization of the drug occurred in all of the solid dispersions of Fluvastatin as a result of drug dissolution into polymer matrices and due to physical interactions (hydrogen bonding) between the polymer matrix and Fluvastatin. This was established through the use of FTIR spectroscopy. SEM and micro-Raman spectroscopy showed that Fluvastatin was interspersed to the polymer matrices in the form of molecular dispersion and nanodispersion, too. The finding that completely different polymer matrices, used here as drug carriers, produce completely different dissolution profiles for each one of the solid dispersions, suggests that each matrix follows a different drug release mechanism. Hydrogen bonding interactions as in the case of CS/Fluva solid dispersions lead to controlled release profiles. All formulations were subjected to accelerated aging in order to evaluate Fluvastatin stability. From by-products analysis it was found that Fluvastatin is very unstable during storage and anti-isomer as well as lactones are the main formed by-products. On the other hand, solid dispersions due to the evolved interactions of their reactive groups with Fluvastatin provide a sufficient physical and chemical stability. The extent of interactions seems to play the most important role in the drug stabilization.
以聚乙烯吡咯烷酮（PVP）、丙烯酸树脂RS100（Eud）和壳聚糖（CS）作为药物载体基质，采用不同技术制备了氟伐他汀固体分散体，以评估它们在储存期间对氟伐他汀稳定性的影响。使用差示扫描量热法（DSC）和广角X射线衍射法（WAXD）对这三种不同体系进行了表征。结果表明，在所有氟伐他汀固体分散体中均发生了药物的非晶化，这是由于药物溶解到聚合物基质中以及聚合物基质与氟伐他汀之间的物理相互作用（氢键）所致。这是通过傅里叶变换红外光谱（FTIR）确定的。扫描电子显微镜（SEM）和显微拉曼光谱表明，氟伐他汀也以分子分散和纳米分散的形式散布在聚合物基质中。这里用作药物载体的完全不同的聚合物基质为每种固体分散体产生完全不同的溶出曲线，这一发现表明每种基质遵循不同的药物释放机制。如在CS/氟伐他汀固体分散体的情况下，氢键相互作用导致控释曲线。对所有制剂进行加速老化以评估氟伐他汀的稳定性。通过副产物分析发现，氟伐他汀在储存期间非常不稳定，反式异构体和内酯是主要形成的副产物。另一方面，由于其反应基团与氟伐他汀之间的相互作用，固体分散体提供了足够的物理和化学稳定性。相互作用的程度似乎在药物稳定化中起最重要的作用。
