Pharmaceutics and Industrial Pharmacy Department, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.
Int J Nanomedicine. 2012;7:2483-96. doi: 10.2147/IJN.S28307. Epub 2012 May 17.
Solid lipid nanoparticles (SLNs) formulated from one type of lipid (homolipid) suffer from low drug encapsulation and drug bursting due to crystallization of the lipid into the more ordered β modification, which leads to decreased drug entrapment and faster drug release. This study assessed the feasibility of using nanostructured lipid matrices (NLMs) for ocular delivery of methazolamide-(MZA) adopting heterolipids composed of novel mixtures of Compritol (®) and cetostearyl alcohol (CSA), and stabilized by Tween 80(®). The systems were prepared using the modified high shear homogenization followed by ultrasonication method, which avoids the use of organic solvents. A 3(2) full factorial design was constructed to study the influence of two independent variables, namely the ratio of CSA:Compritol and the concentration of Tween 80, each in three levels. The dependent variables were the entrapment efficiency percentages (EE%), mean particle size (PS), polydispersity index (PDI), and zeta potential (ZP). In vivo intraocular pressure (IOP) lowering activity for the selected formulae was compared to that of MZA solution. The results showed that increasing the ratio of CSA to Compritol increased the EE% and PS, while increasing the concentration of Tween 80, decreased PS with no significant effect on EE%. The ZP values of all formulae were positive, and greater than 30 mV. The best formula, composed of 4% CSA, 2% Compritol, 0.15% stearylamine, and 2% Tween 80, with EE% of 25.62%, PS of 207.1 nm, PDI of 0.243, and ZP of 41.50 mV, showed in vitro sustained release properties for 8 hours and lowered the intraocular pressure by 8.3 mmHg within 3 hours, with this drop in pressure lasting for 12 hours.
固体脂质纳米粒 (SLNs) 由一种脂质（同型脂质）制成，由于脂质结晶成更有序的β 态，导致药物包封率低和药物突释，从而降低药物包封率和加快药物释放。本研究评估了使用纳米结构脂质基质 (NLMs) 传递甲唑胺 (MZA) 的可行性，采用新型 Compritol(®)和鲸蜡硬脂醇 (CSA) 混合物组成的异质脂质，并由吐温 80(®)稳定。该系统采用改良的高剪切匀化后超声法制备，避免使用有机溶剂。构建了一个 3(2) 完全因子设计，以研究两个独立变量（即 CSA:Compritol 的比例和吐温 80 的浓度）的影响，每个变量有三个水平。依赖变量是包封效率百分比（EE%）、平均粒径（PS）、多分散指数（PDI）和 zeta 电位（ZP）。所选配方的体内眼压 (IOP) 降低活性与 MZA 溶液进行了比较。结果表明，增加 CSA 与 Compritol 的比例会增加 EE%和 PS，而增加吐温 80 的浓度会降低 PS，但对 EE%没有显著影响。所有配方的 ZP 值均为正，大于 30 mV。最佳配方由 4% CSA、2% Compritol、0.15%硬脂胺和 2%吐温 80 组成，EE%为 25.62%、PS 为 207.1nm、PDI 为 0.243、ZP 为 41.50 mV，表现出 8 小时的体外持续释放特性，并在 3 小时内降低眼内压 8.3mmHg，这种眼压下降持续 12 小时。
