Bunjes Heike, Koch Michel H J
Friedrich Schiller University Jena, Institute of Pharmacy, Department of Pharmaceutical Technology, Lessingstrasse 8, D-07743 Jena, Germany.
J Control Release. 2005 Oct 3;107(2):229-43. doi: 10.1016/j.jconrel.2005.06.004.
Some matrix materials proposed for the preparation of solid lipid nanoparticles (e.g. trilaurin) are difficult to crystallize after processing by melt-homogenization. In an attempt to overcome this difficulty, the effect of saturated long-chain phospholipids on the crystallization of nanoparticles based on trilaurin, trimyristin, tripalmitin and tristearin was studied. The phospholipids were used as emulsifiers in combination with sodium glycocholate. Saturated phospholipids increased the crystallization temperature of the triglyceride by several degrees compared to soybean phospholipids. The crystallization pattern was more complex in such systems due to solidification of the phospholipid chains prior to triglyceride crystallization. For most triglycerides, egg lecithin also induced crystallization at higher temperatures than natural soybean lecithin. With trilaurin dispersions, the effect of phospholipids can be utilized to induce crystallization at temperatures relevant for larger scale preparation. The polymorphic transitions of the triglycerides were slower in the presence of egg and saturated lecithin leading to a higher stability of the metastable alpha-form. These effects were particularly pronounced in tristearin systems where a predominant fraction of alpha-phase particles could be observed even after long-term cold storage in dispersions containing hydrogenated soybean lecithin or DPPC. The possibility to prepare triglyceride nanoparticles stable in specific modifications offers new opportunities to study effects of polymorphic form on colloidal stability, drug loading and release properties of such dispersions.
一些被提议用于制备固体脂质纳米粒的基质材料（如甘油三酯）在通过熔融均质法加工后难以结晶。为了克服这一困难，研究了饱和长链磷脂对基于甘油三酯（三酰甘油）、三肉豆蔻酸甘油酯、三棕榈酸甘油酯和三硬脂酸甘油酯的纳米粒结晶的影响。这些磷脂与甘氨胆酸钠联合用作乳化剂。与大豆磷脂相比，饱和磷脂使甘油三酯的结晶温度提高了几度。由于在甘油三酯结晶之前磷脂链就已固化，此类体系中的结晶模式更为复杂。对于大多数甘油三酯而言，与天然大豆卵磷脂相比，蛋黄卵磷脂也能在更高温度下诱导结晶。对于三酰甘油分散体，磷脂的作用可被用于在与大规模制备相关的温度下诱导结晶。在蛋黄卵磷脂和饱和卵磷脂存在的情况下，甘油三酯的多晶型转变较慢，从而导致亚稳α晶型具有更高的稳定性。这些效应在三硬脂酸甘油酯体系中尤为明显，在含有氢化大豆卵磷脂或二棕榈酰磷脂酰胆碱的分散体中，即使经过长期冷藏，也能观察到主要部分为α相的颗粒。制备特定晶型稳定的甘油三酯纳米粒的可能性为研究多晶型对这类分散体的胶体稳定性、药物负载和释放特性的影响提供了新的机会。
