Liew Celine Valeria, Chan Lai Wah, Ching Ai Ling, Heng Paul Wan Sia
Department of Pharmacy, Faculty of Science, National University of Singapore, 18 Science Drive 4, Singapore 117543, Singapore.
Int J Pharm. 2006 Feb 17;309(1-2):25-37. doi: 10.1016/j.ijpharm.2005.10.040. Epub 2005 Dec 20.
Alginates are useful natural polymers suitable for use in the design of pharmaceutical dosage forms. However, the effects of particle size, viscosity and chemical composition of alginates on drug release from alginate matrix tablets are not clearly understood. Hence, 17 grades of sodium alginate with different particle size distributions, viscosities and chemical compositions were used to prepare matrix tablets at various concentrations to screen the factors influencing drug release from such matrices. Particle size was found to have an influence on drug release from these matrices. Sodium alginate was subsequently classified into several size fractions and also cryogenically milled to produce smaller particle size samples. Cryogenic milling could be successfully applied to pulverize coarse alginate particles without changing the quality through degradation or segregation. This study showed the significance of each alginate property in modulating drug release: particle size is important in initial alginic acid gel barrier formation as it affected the extent of burst release; higher alginate viscosity slowed down drug release rate in the buffer phase but enhanced release rate in the acid phase; high M-alginate might be more advantageous than high-G-alginate in sustaining drug release; and, the effect of increasing alginate concentration was greater with larger alginate particles. This can serve as a framework for formulators working with alginates. Furthermore, the results showed that sodium alginate matrices can sustain drug release for at least 8 h, even for a highly water-soluble drug in the presence of a water-soluble excipient.
海藻酸盐是适用于药物剂型设计的有用天然聚合物。然而，海藻酸盐的粒径、粘度和化学组成对海藻酸盐基质片剂中药物释放的影响尚未完全清楚。因此，使用17种具有不同粒径分布、粘度和化学组成的海藻酸钠等级，以不同浓度制备基质片剂，以筛选影响此类基质中药物释放的因素。发现粒径对这些基质中的药物释放有影响。随后将海藻酸钠分为几个粒径级分，并进行低温研磨以制备更小粒径的样品。低温研磨可成功用于粉碎粗海藻酸盐颗粒，而不会因降解或分离而改变质量。本研究表明了每种海藻酸盐性质在调节药物释放中的重要性：粒径在初始海藻酸凝胶屏障形成中很重要，因为它影响突释程度；较高的海藻酸盐粘度在缓冲阶段减缓了药物释放速率，但在酸性阶段提高了释放速率；在维持药物释放方面，高M-海藻酸盐可能比高G-海藻酸盐更具优势；并且，海藻酸盐颗粒越大，海藻酸盐浓度增加的影响越大。这可以作为使用海藻酸盐的配方设计师的一个框架。此外，结果表明，即使在存在水溶性辅料的情况下，对于高水溶性药物，海藻酸钠基质也可以维持药物释放至少8小时。
