College of Pharmacy, Yeungnam University, Gyongsan, South Korea.
Eur J Pharm Biopharm. 2012 Feb;80(2):289-97. doi: 10.1016/j.ejpb.2011.11.005. Epub 2011 Nov 18.
In order to investigate the effects of solid carriers on the crystalline properties, dissolution and bioavailability of flurbiprofen in a solid self-nanoemulsifying drug delivery system (solid SNEDDS), different solid SNEDDS formulations were prepared by spray-drying the solutions containing liquid SNEDDS and various carriers. The liquid SNEDDS, composed of Labrafil M 1944 CS/Labrasol/Trasncutol HP (12.5/80/7.5%) with 2%w/v flurbiprofen, gave a z-average diameter of about 100 nm. Silicon dioxide, a hydrophobic solid carrier, produced an excellent conventional solid SNEDDS with a nanoemulsion droplet size of less than 100 nm, similar to the liquid SNEDDS and smaller than the other solid SNEDDS formulations. The drug was in an amorphous state in this solid SNEDDS. Furthermore, it greatly improved the dissolution rate and oral bioavailability of flurbiprofen in rats because it allowed the spontaneous formation of an interface between the oil droplets and the water. Magnesium stearate, a hydrophobic carrier, produced a solid SNEDDS with the largest diameter. However, it greatly enhanced the dissolution rate and oral bioavailability due to the formation of a simple eutectic mixture. The hydrophilic carriers such as polyvinyl alcohol (PVA), sodium carboxymethyl cellulose (Na-CMC) and hydroxypropyl-β-cyclodextrantrin (HP-β-CD) did not form a solid SNEDDS but rather a solid dispersion (or microcapsule). HP-β-CD improved the dissolution rate but did not improve the oral bioavailability as much as the hydrophobic polymers. PVA and Na-CMC hardly improved the dissolution rate but maintained constantly high plasma levels in rats for a long period. Thus, the selection of carrier is an important factor in the development of solid SNEDDS, since the carriers had significant effects on the crystalline properties, dissolution and oral bioavailability of flurbiprofen and on the formation of solid SNEDDS.
为了研究固体载体对氟比洛芬在固体自微乳释药系统（固体 SNEDDS）中结晶性质、溶出度和生物利用度的影响，通过喷雾干燥含有液体 SNEDDS 和各种载体的溶液制备了不同的固体 SNEDDS 制剂。液体 SNEDDS 由 Labrafil M 1944 CS/Labrasol/Trasncutol HP（12.5/80/7.5%）与 2%w/v 氟比洛芬组成，粒径约为 100nm。疏水性固体载体二氧化硅产生了极好的常规固体 SNEDDS，其纳米乳液粒径小于 100nm，与液体 SNEDDS 相似且小于其他固体 SNEDDS 制剂。药物在这种固体 SNEDDS 中处于无定形状态。此外，由于它允许油滴和水之间自发形成界面，因此大大提高了氟比洛芬在大鼠中的溶出速率和口服生物利用度。硬脂酸镁，一种疏水性载体，产生了最大粒径的固体 SNEDDS。然而，由于形成了简单的共晶混合物，它大大提高了溶出速率和口服生物利用度。亲水性载体如聚乙烯醇（PVA）、羧甲基纤维素钠（Na-CMC）和羟丙基-β-环糊精（HP-β-CD）没有形成固体 SNEDDS，而是形成了固体分散体（或微胶囊）。HP-β-CD 提高了溶出速率，但不如疏水性聚合物那样提高口服生物利用度。PVA 和 Na-CMC 几乎没有提高溶出速率，但在很长一段时间内使大鼠的血浆水平保持在较高水平。因此，载体的选择是固体 SNEDDS 开发的一个重要因素，因为载体对氟比洛芬的结晶性质、溶出度和口服生物利用度以及固体 SNEDDS 的形成有显著影响。
