Lu Jiannan, Cuellar Kristina, Hammer Nathan I, Jo Seongbong, Gryczke Andreas, Kolter Karl, Langley Nigel, Repka Michael A
a Department of Pharmaceutics and Drug Delivery , School of Pharmacy, the University of Mississippi, University , MS , USA .
b Department of Chemistry and Biochemistry , The University of Mississippi, University , MS , USA .
Drug Dev Ind Pharm. 2016;42(3):485-96. doi: 10.3109/03639045.2015.1104347. Epub 2015 Nov 4.
The aim of the current study is to develop amorphous solid dispersion (SD) via hot melt extrusion technology to improve the solubility of a water-insoluble compound, felodipine (FEL). The solubility was dramatically increased by preparation of amorphous SDs via hot-melt extrusion with an amphiphilic polymer, Soluplus® (SOL). FEL was found to be miscible with SOL by calculating the solubility parameters. The solubility of FEL within SOL was determined to be in the range of 6.2-9.9% (w/w). Various techniques were applied to characterize the solid-state properties of the amorphous SDs. These included Fourier Transform Infrared Spectrometry spectroscopy and Raman spectroscopy to detect the formation of hydrogen bonding between the drug and the polymer. Scanning electron microscopy was performed to study the morphology of the SDs. Among all the hot-melt extrudates, FEL was found to be molecularly dispersed within the polymer matrix for the extrudates containing 10% drug, while few small crystals were detected in the 30 and 50% extrudates. In conclusion, solubility of FEL was enhanced while a homogeneous SD was achieved for 10% drug loading.
本研究的目的是通过热熔挤出技术制备无定形固体分散体（SD），以提高水不溶性化合物非洛地平（FEL）的溶解度。通过与两亲性聚合物Soluplus®（SOL）进行热熔挤出制备无定形SD，显著提高了FEL的溶解度。通过计算溶解度参数发现FEL与SOL可混溶。FEL在SOL中的溶解度测定为6.2 - 9.9%（w/w）。应用了各种技术来表征无定形SD的固态性质。这些技术包括傅里叶变换红外光谱法和拉曼光谱法，以检测药物与聚合物之间氢键的形成。进行扫描电子显微镜观察以研究SD的形态。在所有热熔挤出物中，对于含10%药物的挤出物，发现FEL分子分散在聚合物基质中，而在含30%和50%药物的挤出物中检测到少量小晶体。总之，对于10%的药物负载量，FEL的溶解度得到了提高，同时实现了均匀的SD。
