Karavas Evangelos, Georgarakis Manolis, Docoslis Aristides, Bikiaris Dimitrios
Pharmathen S.A., Pharmaceutical Industry, Dervenakion Str. 6, Pallini Attikis, 153 51 Attiki, Greece.
Int J Pharm. 2007 Aug 1;340(1-2):76-83. doi: 10.1016/j.ijpharm.2007.03.037. Epub 2007 Mar 30.
The aim of the present study was to experimentally examine whether poorly water-soluble drugs dispersed in a polymeric matrix exist as amorphous nanodispersions or molecularly dispersed compounds. Felodipine (Felo) dispersed in PVP matrix (solid dispersion) was used as a model drug in this study. Drug/polymer ratios have an impact on the drug average particle size, morphology and dissolution profile while solid dispersions containing up to 50wt% Felo are completely amorphous. SEM, TEM micrographs, and micro-Raman mapping reveal that Felo is dispersed in the form of nanoparticles into the PVP matrix. Due to the high spatial resolution of TEM, it was established that these nanoparticles are not uniform particles, but rather agglomerates of individual particles with sizes smaller than 5-10nm. Moreover, micro-Raman mapping allowed us to observe the size and spatial distribution of domains where the drug existed as molecularly or nanodispersed. Experimental evidence presented in this work contradicts the common belief that amorphous poorly water-soluble drugs exist only in the state of molecular dispersion inside a polymer matrix by showing that both types of dispersions (molecular-level and nanodispersions) can coexist.
本研究的目的是通过实验检验分散在聚合物基质中的难溶性药物是以无定形纳米分散体还是分子分散化合物的形式存在。本研究中使用分散在聚乙烯吡咯烷酮（PVP）基质（固体分散体）中的非洛地平（Felo）作为模型药物。药物/聚合物比例会影响药物的平均粒径、形态和溶出曲线，而含高达50wt% Felo的固体分散体完全是无定形的。扫描电子显微镜（SEM）、透射电子显微镜（TEM）照片以及显微拉曼光谱映射显示，Felo以纳米颗粒的形式分散在PVP基质中。由于TEM具有高空间分辨率，已确定这些纳米颗粒不是均匀的颗粒，而是由尺寸小于5 - 10nm的单个颗粒聚集而成。此外，显微拉曼光谱映射使我们能够观察到药物以分子或纳米分散形式存在的区域的大小和空间分布。本研究中给出的实验证据与一种普遍观点相矛盾，该观点认为无定形难溶性药物仅以分子分散状态存在于聚合物基质中，而本研究表明两种分散形式（分子水平和纳米分散）可以共存。
