Institute of Pharmaceutics and Biopharmaceutics, Heinrich-Heine-University Düsseldorf, Germany; Centre for Drug Research, Faculty of Pharmacy, University of Helsinki, Finland; Division of Pharmaceutical Technology, Faculty of Pharmacy, University of Helsinki, Finland.
Int J Pharm. 2009 Nov 3;381(2):184-91. doi: 10.1016/j.ijpharm.2009.03.002. Epub 2009 Mar 19.
A monoacid triglyceride and a partial glyceride were extruded below their melting ranges alone and together in different mixture ratios to investigate the influence of the chemical composition of the lipid matrix on the solid-state properties and dissolution characteristics. The partial glyceride exhibits a faster release of the drug compared to the triglyceride due to its surfactant properties. The lipid mixtures show rather complex solid-state behaviour and hence unexpected dissolution characteristics. Adding 10% (w/w) partial glyceride to a triglyceride matrix led to increased incidence of the unstable alpha-form of the triglyceride leading to recrystallization of the stable beta-form over time which causes fractal structures on the extrudate surface which decrease the dissolution rate. Adding 50% (w/w) partial glyceride to the triglyceride matrix also results in tristearin alpha-formation subsequently followed by recrystallization to the beta-form. But as 50% of the matrix consists of the partial glyceride the dissolution rate was faster than the rate obtained by pure triglyceride or the 9+1 (w/w) mixture of triglyceride and partial glyceride. The results of this study help in understanding the complex solid-state behaviour of solid lipid extrudates with different composition and to manufacture suitable lipid-based oral dosage forms.
单独和以不同混合比例将单酸甘油三酯和部分甘油酯挤压到低于其熔点以下，以研究脂质基质的化学成分对固体状态性质和溶解特性的影响。由于部分甘油酯具有表面活性剂的性质，因此与甘油三酯相比，它具有更快的药物释放速度。脂质混合物表现出相当复杂的固态行为，因此具有意想不到的溶解特性。向甘油三酯基质中添加 10%（w/w）的部分甘油酯会导致甘油三酯不稳定的α形式的发生率增加，从而导致稳定的β形式在一段时间内重新结晶，这会导致挤出物表面出现分形结构，从而降低溶解速率。向甘油三酯基质中添加 50%（w/w）的部分甘油酯也会导致三硬脂酸甘油酯的α形成，随后再结晶为β形式。但是，由于基质的 50%由部分甘油酯组成，因此溶解速度比纯甘油三酯或甘油三酯和部分甘油酯的 9+1（w/w）混合物的速度更快。这项研究的结果有助于理解具有不同组成的固体脂质挤出物的复杂固态行为，并制造合适的基于脂质的口服剂型。
