Dong Bingxue, Hadinoto Kunn
School of Chemical and Biomedical Engineering, Nanyang Technological University, 637459, Singapore.
School of Chemical and Biomedical Engineering, Nanyang Technological University, 637459, Singapore.
Int J Pharm. 2017 May 15;523(1):42-51. doi: 10.1016/j.ijpharm.2017.03.021. Epub 2017 Mar 19.
Amorphous drug-polysaccharide nanoparticle complex (or drug nanoplex) had emerged as an ideal supersaturating delivery system of poorly-soluble drugs attributed to its many attractive characteristics. Herein we presented for the first time direct comparison between two nanoplex synthesis platforms, i.e. millifluidics and bulk mixing, representing continuous and batch production modes, respectively. They were compared by the resultant nanoplex's (1) physical characteristics (size, zeta potential, and payload), (2) preparation efficiency, (3) storage stability, (4) dissolution rate/supersaturation generation, and (5) production consistency. The effects of key variables in drug-polysaccharide complexation (pH, charge ratio) were investigated in both platforms. Perphenazine and dextran sulfate were used as the drug and polysaccharide models, respectively. The results showed that both platforms shared similar dependences on pH and charge ratio with similar optimal preparation conditions, where the pH was the governing variable through its influence on size and zeta potential, Nanoplexes having mostly similar characteristics (size ≈70-90nm, zeta potential ≈-50mV) were produced by both platforms, except for the payload where bulk mixing resulted in lower payload (65% versus 85%). The lower payload, however, resulted in its superior supersaturation generation. Nevertheless, millifluidics was favored attributed to its superior production consistency and scalability.
无定形药物 - 多糖纳米颗粒复合物（或药物纳米复合物）因其诸多吸引人的特性，已成为难溶性药物理想的过饱和递送系统。在此，我们首次对两种纳米复合物合成平台进行了直接比较，即微流控和批量混合，它们分别代表连续和间歇生产模式。通过所得纳米复合物的以下方面对它们进行比较：（1）物理特性（尺寸、zeta电位和载药量），（2）制备效率，（3）储存稳定性，（4）溶解速率/过饱和生成，以及（5）生产一致性。在两个平台上均研究了药物 - 多糖络合过程中关键变量（pH值、电荷比）的影响。分别使用奋乃静和硫酸葡聚糖作为药物和多糖模型。结果表明，两个平台对pH值和电荷比具有相似的依赖性，且具有相似的最佳制备条件，其中pH值通过对尺寸和zeta电位的影响而成为主导变量。两个平台制备的纳米复合物大多具有相似的特性（尺寸≈70 - 90nm，zeta电位≈ - 50mV），但批量混合制备的纳米复合物载药量较低（65%对85%）。然而，较低的载药量导致其过饱和生成能力更强。尽管如此，微流控因其卓越的生产一致性和可扩展性而更受青睐。
