Otto H. York Department of Chemical and Materials Engineering, New Jersey Institute of Technology, University Heights, Newark, NJ 07012, USA.
Otto H. York Department of Chemical and Materials Engineering, New Jersey Institute of Technology, University Heights, Newark, NJ 07012, USA.
Eur J Pharm Biopharm. 2019 Dec;145:12-26. doi: 10.1016/j.ejpb.2019.10.002. Epub 2019 Oct 14.
A major shortcoming of drug nanocomposites as compared with amorphous solid dispersions (ASDs) is their limited supersaturation capability in dissolution media. Here, we prepared drug hybrid nanocrystal-amorphous solid dispersions (HyNASDs) and compare their performance to ASDs. A wet-milled griseofulvin (GF, BCS II drug) nanosuspension and a GF solution, both containing the same dissolved polymer-surfactant (SDS: sodium dodecyl sulfate) with 1:1 and 1:3 GF:polymer mass ratios, were spray-dried. Hydroxypropyl cellulose (HPC) and Soluplus (Sol) were used as matrix-forming polymers. XRPD, DSC, and Raman spectroscopy reveal that ASDs were formed upon spray-drying the solution-based feed, whereas nanocomposites and nanocomposites with >10% amorphous content, HyNASDs, were formed with the nanosuspension-based feed. Sol provided higher GF relative supersaturation, up to 180% and 360% for HyNASDs and ASDs, respectively, in the dissolution tests than HPC (up to 50% for both) owing to Sol's stronger intermolecular interactions and miscibility with GF and its recrystallization inhibition. Besides the higher kinetic solubility of GF in Sol, presence of GF nanoparticles vs. micron-sized particles in the nanocomposites enabled fast supersaturation. This study demonstrates successful preparation of fast supersaturating (190% within 20 min) HyNASDs, which renders nanoparticle formulations competitive to ASDs in bioavailability enhancement of poorly soluble drugs.
与无定形固体分散体（ASD）相比，药物纳米复合材料的一个主要缺点是其在溶解介质中的过饱和度能力有限。在这里，我们制备了药物杂化纳米晶-无定形固体分散体（HyNASD），并将其性能与 ASD 进行了比较。将含有相同溶解聚合物-表面活性剂（SDS：十二烷基硫酸钠）的灰黄霉素（BCS II 药物）纳米混悬液和灰黄霉素溶液（GF：聚合物质量比为 1:1 和 1:3）进行湿磨，然后喷雾干燥。羟丙基纤维素（HPC）和 Soluplus（Sol）用作基质形成聚合物。XRPD、DSC 和拉曼光谱表明，溶液型进料喷雾干燥后形成 ASD，而纳米混悬型进料喷雾干燥后形成纳米复合材料和含有>10%无定形含量的纳米复合材料，HyNASD。Sol 提供了更高的 GF 相对过饱和度，在溶解试验中，HyNASD 和 ASD 的相对过饱和度分别高达 180%和 360%，而 HPC 的相对过饱和度最高为 50%（两者均为 50%），这是由于 Sol 与 GF 具有更强的分子间相互作用和混溶性，以及其对再结晶的抑制作用。除了 GF 在 Sol 中的动力学溶解度更高之外，纳米复合材料中存在 GF 纳米颗粒而不是微米级颗粒，这使得过饱和度能够快速达到。本研究成功制备了快速过饱和（20 分钟内达到 190%）的 HyNASD，这使得纳米粒子制剂在提高难溶性药物的生物利用度方面具有竞争力，可与 ASD 相媲美。
