Wu Tian, Sun Ye, Li Ning, de Villiers Melgardt M, Yu Lian
School of Pharmacy, University of Wisconsin-Madison, 777 Highland Avenue, Madison, Wisconsin 53705-2222, USA.
Langmuir. 2007 Apr 24;23(9):5148-53. doi: 10.1021/la070050i. Epub 2007 Mar 31.
An amorphous solid (glass) may crystallize faster at the surface than through the bulk, making surface crystallization a mechanism of failure for amorphous pharmaceuticals and other materials. An ultrathin coating of gold or polyelectrolytes inhibited the surface crystallization of amorphous indomethacin (IMC), an anti-inflammatory drug and model organic glass. The gold coating (10 nm) was deposited by sputtering, and the polyelectrolyte coating (3-20 nm) was deposited by an electrostatic layer-by-layer assembly of cationic poly(dimethyldiallyl ammonium chloride) (PDDA) and anionic sodium poly(styrenesulfonate) (PSS) in aqueous solution. The coating also inhibited the growth of existing crystals. The inhibition was strong even with one layer of PDDA. The polyelectrolyte coating still permitted fast dissolution of amorphous IMC and improved its wetting and flow. The finding supports the view that the surface crystallization of amorphous IMC is enabled by the mobility of a thin layer of surface molecules, and this mobility can be suppressed by a coating of only a few nanometers. This technique may be used to stabilize amorphous drugs prone to surface crystallization, with the aqueous coating process especially suitable for drugs of low aqueous solubility.
非晶态固体（玻璃）在表面的结晶速度可能比在整体中更快，这使得表面结晶成为非晶态药物和其他材料失效的一种机制。金或聚电解质的超薄涂层抑制了非晶态吲哚美辛（IMC，一种抗炎药物和典型的有机玻璃）的表面结晶。金涂层（10纳米）通过溅射沉积，聚电解质涂层（3 - 20纳米）通过阳离子聚（二甲基二烯丙基氯化铵）（PDDA）和阴离子聚苯乙烯磺酸钠（PSS）在水溶液中进行静电逐层组装沉积。该涂层还抑制了现有晶体的生长。即使只有一层PDDA，这种抑制作用也很强。聚电解质涂层仍然允许非晶态IMC快速溶解，并改善了其润湿性和流动性。这一发现支持了这样一种观点，即非晶态IMC的表面结晶是由表面分子薄层的流动性促成的，而这种流动性可以被仅几纳米厚的涂层所抑制。该技术可用于稳定易于表面结晶的非晶态药物，水性涂层工艺尤其适用于低水溶性药物。
