Otto H. York Department of Chemical, Biological, and Pharmaceutical Engineering, New Jersey Institute of Technology, 161 Warren St. 150 Tiernan Hall, Newark, New Jersey, 07102, USA.
AAPS PharmSciTech. 2018 Jan;19(1):436-447. doi: 10.1208/s12249-017-0850-x. Epub 2017 Aug 2.
Nanocomposite microparticles (NCMPs) have been used in various solid dosage forms with the goal of enhancing the dissolution rate and bioavailability of poorly water-soluble drugs. Nanoparticle recovery from NCMPs, i.e., redispersion, is the preliminary step in drug dissolution. This study aims at exploring aqueous redispersion of NCMPs with various dispersants under quiescent vs. agitated conditions as potential dispersant screening tool in the development of fast-dissolving NCMP formulations. NCMPs were prepared by coating wet-milled suspensions of a poorly water-soluble drug, griseofulvin (GF), formulated with the dispersants hydroxypropyl cellulose (HPC), sodium dodecyl sulfate (SDS), as-received/wet co-milled croscarmellose sodium (CCS), and mannitol, onto Pharmatose® carrier particles in a fluidized bed dryer. The NCMPs were added to quiescent water kept in a cuvette, and the redispersion was visualized and investigated by turbidimetry and dynamic light scattering. The morphological evolution of a single NCMP exposed to a drop of water was studied via optical microscopy, which provided further insight into the self-redispersibility. As a comparison, the NCMPs were also redispersed in water agitated by a paddle stirrer followed by centrifugation and drug assay of the resultant supernatant, which yielded the percentage of GF recovered as nanoparticles. Both quiescent and agitated redispersion methods yielded similar rank-ordering of the dispersants: NCMPs with either HPC/SDS or HPC/CCS exhibited effective nanoparticle recovery and fast dissolution, whereas those with HPC or HPC/mannitol led to poor redispersibility and slow dissolution. This study demonstrates that both quiescent and agitated redispersion tests could be used for screening/optimizing dispersants for fast-dissolving drug NCMP formulations.
纳米复合微粒（NCMP）已被应用于各种固体制剂中，旨在提高难溶性药物的溶解速率和生物利用度。NCMP 中纳米颗粒的回收，即再分散，是药物溶解的初步步骤。本研究旨在探索不同分散剂在静止和搅拌条件下对 NCMP 的水相再分散，作为开发快速溶解 NCMP 制剂的潜在分散剂筛选工具。NCMP 通过将难溶性药物灰黄霉素（GF）的湿磨混悬液包衣到 Pharmatose®载体颗粒上，用羟丙纤维素（HPC）、十二烷基硫酸钠（SDS）、未经湿磨的共磨羧甲纤维素钠（CCS）和甘露醇等分散剂进行制剂，在流化床干燥器中制备。将 NCMP 添加到置于比色皿中的静止水中，通过浊度法和动态光散射法对再分散进行可视化和研究。通过光学显微镜研究了暴露于一滴水的单个 NCMP 的形态演变，这为自再分散性提供了进一步的见解。作为比较，还通过桨式搅拌器搅拌使 NCMP 在水中再分散，然后离心并对所得上清液进行药物测定，得出以纳米颗粒形式回收的 GF 百分比。静止和搅拌再分散方法均得出相似的分散剂排序：用 HPC/SDS 或 HPC/CCS 制备的 NCMP 表现出有效的纳米颗粒回收和快速溶解，而用 HPC 或 HPC/甘露醇制备的 NCMP 则表现出较差的再分散性和缓慢溶解。本研究表明，静止和搅拌再分散试验均可用于筛选/优化快速溶解药物 NCMP 制剂的分散剂。
