Institute of Pharmacy, Department of Pharmaceutics, Biopharmaceutics & NutriCosmetics, Freie Universität Berlin, Kelchstr. 31, 12169 Berlin, Germany.
Institute of Pharmacy, Department of Pharmaceutics, Biopharmaceutics & NutriCosmetics, Freie Universität Berlin, Kelchstr. 31, 12169 Berlin, Germany; Fachhochschule/University of Applied Sciences Kaiserslautern, Carl-Schurz-Str. 10-16, 66953 Pirmasens, Germany.
Int J Pharm. 2015 Mar 30;482(1-2):11-20. doi: 10.1016/j.ijpharm.2014.10.068. Epub 2014 Nov 25.
The CapsMorph(®) technology prepares amorphous drugs for oral delivery by encapsulating them into porous materials. Hesperidin as model compound was loaded onto AEROPERL(®) 300 Pharma using the wetness impregnation method. Hesperidin was dissolved in dimethyl sulfoxide (DMSO) and alternatively in DMSO with addition of Tween 80. The drug solutions were added dropwise to the porous material and subsequently DMSO was evaporated. The AEROPERL(®) 300 Pharma could be loaded with about 30% hesperidin in the amorphous form. Amorphous state was verified by X-ray diffraction and differential scanning calorimetry. The CapsMorph(®) formulation was compared regarding properties determining oral bioavailability, i.e., kinetic saturation solubility and dissolution rate to raw drug powder and hesperidin nanocrystals. The saturation solubility of CapsMorph(®) without Tween 80 was 654 μg/ml, which is 36-fold higher than the raw drug powder (18 μg/ml) and about 20 times higher than nanocrystals (30 μg/ml). In vitro release was faster (100% in 10 min at pH 6.8) compared to dissolution of nanocrystals with about 15%. Addition of Tween 80 to CapsMorph(®) lowered the solubility (168 μg/ml) and slowed down the release, but provided longer times of supersaturation without precipitation of drug. Based on these data, it appears that drug loaded porous materials provide better formulations compared to nanocrystals for poorly soluble drugs.
CapsMorph(®) 技术通过将无定形药物包封到多孔材料中，为口服给药做好准备。以橙皮苷为模型化合物，采用湿法浸渍法将其载入 AEROPERL(®) 300 Pharma。橙皮苷溶于二甲基亚砜 (DMSO) 中，或者在 DMSO 中加入吐温 80。将药物溶液逐滴加入多孔材料中，然后蒸发 DMSO。AEROPERL(®) 300 Pharma 可以负载约 30%的无定形橙皮苷。无定形状态通过 X 射线衍射和差示扫描量热法进行验证。将 CapsMorph(®) 制剂与原料药粉末和橙皮苷纳米晶体的性质进行了比较，这些性质决定了口服生物利用度，即动力学饱和溶解度和溶解速率。无 Tween 80 的 CapsMorph(®) 的饱和溶解度为 654 μg/ml，是原料药粉末（18 μg/ml）的 36 倍，约是纳米晶体（30 μg/ml）的 20 倍。与纳米晶体相比（约 15%），在 pH 6.8 下 10 分钟内即可达到 100%的体外释放速度更快。添加 Tween 80 会降低 CapsMorph(®) 的溶解度（168 μg/ml）并减缓释放速度，但会提供更长时间的过饱和度而不会发生药物沉淀。基于这些数据，似乎对于难溶性药物而言，负载多孔材料的药物比纳米晶体提供了更好的制剂。
