Jindal Anil B, Devarajan Padma V
Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Matunga (E), Mumbai 400019, India.
Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Matunga (E), Mumbai 400019, India.
Int J Pharm. 2015 Jul 15;489(1-2):246-51. doi: 10.1016/j.ijpharm.2015.04.073. Epub 2015 Apr 28.
Asymmetric lipid polymer nanostructures (LIPOMER) comprising glyceryl monostearate (GMS) as lipid and Gantrez AN 119 (Gantrez) as polymer, revealed enhanced splenic accumulation. In the present paper, we attempt to explain the formation of asymmetric GMS LIPOMER using real time imaging. Particles were prepared by precipitation under static conditions using different non-solvent phase compositions. The process was video recorded and the videos converted to time elapsed images using the FFmpeg 0.10.2 software at 25 frames/sec. Non-solvent compositions comprising >30% of IPA/Acetone revealed significant stranding of the solvent phase and slower onset of precipitation(2-6s). At lower concentrations of IPA and acetone, and in non-solvent compositions comprising ethanol/water the stranding phenomenon was not evident. Further, rapid precipitation(<1 s) was evident. Nanoprecipitation based on the Marangoni effect is a result of diffusion stranding, interfacial turbulence, and mass transfer of solvent and non-solvent resulting in solute precipitation. Enhanced diffusion stranding favored by high interaction of GMS and Gantrez(low ΔPol), and the low solubility parameter(Δδtotal) and high mixing enthalpy(ΔHM) of GMS in IPA resulted in droplets with random shapes analogous to an amoeba with pseudopodia, which on precipitation formed asymmetric particles. Asymmetric particles could be readily designed through appropriate selection of solutes and non-solvent phase by modified nanoprecipitation.
由单硬脂酸甘油酯（GMS）作为脂质和甘泰瑞兹AN 119（Gantrez）作为聚合物组成的不对称脂质聚合物纳米结构（LIPOMER）显示出增强的脾脏蓄积。在本文中，我们试图通过实时成像来解释不对称GMS LIPOMER的形成。使用不同的非溶剂相组成在静态条件下通过沉淀制备颗粒。对该过程进行视频记录，并使用FFmpeg 0.10.2软件以25帧/秒的速度将视频转换为时间推移图像。包含>30%异丙醇/丙酮的非溶剂组合物显示出溶剂相的明显滞留和较慢的沉淀开始时间（2-6秒）。在较低浓度的异丙醇和丙酮以及包含乙醇/水的非溶剂组合物中，滞留现象不明显。此外，明显出现快速沉淀（<1秒）。基于马兰戈尼效应的纳米沉淀是扩散滞留、界面湍流以及溶剂和非溶剂的传质导致溶质沉淀的结果。GMS和Gantrez的高相互作用（低ΔPol）、GMS在异丙醇中的低溶解度参数（Δδtotal）和高混合焓（ΔHM）有利于增强的扩散滞留，从而形成形状类似于带有伪足的变形虫的随机形状的液滴，这些液滴在沉淀时形成不对称颗粒。通过改良的纳米沉淀，通过适当选择溶质和非溶剂相可以很容易地设计出不对称颗粒。
