Mäki Riikka, Suihko Eero, Rost Susanne, Heiskanen Minna, Murtomaa Matti, Lehto Vesa-Pekka, Ketolainen Jarkko
Department of Pharmaceutics, University of Kuopio, P.O. Box 1627, FI-70211 Kuopio, Finland.
J Pharm Sci. 2007 Feb;96(2):438-47. doi: 10.1002/jps.20784.
In this study three model drugs (N-acetyl-D-glucosamine (NAG), anhydrous caffeine, and propranolol hydrochloride) were agglomerated with starch acetate (SA) by mixing the binary powders on a stainless steel (SS) plate. Agglomeration was induced by triboelectrification of the particles during mixing, and it was evaluated as a method to achieve controlled drug release rate. These agglomerates, mixed with different amounts of a disintegrant, were compressed into tablets whose dissolution characteristics were determined. Triboelectric measurements showed that when the drugs were in contact with SS, charges of the opposite polarity were generated to SA (+) and caffeine and NAG (-) promoting adhesion. Instead, propranolol HCl was charged with the same polarity as SA. SEM micrographs showed that smaller caffeine particles, in spite of their larger negative charge, agglomerated less efficiently with SA than larger NAG particles. This emphasizes the importance of particle size in the agglomeration process. Propranolol HCl did not form agglomerates with SA since their particle sizes and charges were identical. As a result, agglomeration of powders prior to tablet compression allows for modification and control of the release rate of the drugs from the SA matrix tablets as well as the tensile strength of the tablets.
在本研究中，通过在不锈钢（SS）板上混合二元粉末，将三种模型药物（N-乙酰-D-葡萄糖胺（NAG）、无水咖啡因和盐酸普萘洛尔）与醋酸淀粉（SA）进行团聚。混合过程中颗粒的摩擦起电引发了团聚，并且将其作为一种实现药物释放速率可控的方法进行评估。将这些与不同量崩解剂混合的团聚物压制成片剂，并测定其溶出特性。摩擦电测量表明，当药物与SS接触时，会产生与SA相反极性的电荷（SA带正电，咖啡因和NAG带负电），从而促进粘附。相反，盐酸普萘洛尔带与SA相同极性的电荷。扫描电子显微镜（SEM）照片显示，尽管较小的咖啡因颗粒带较大的负电荷，但与SA的团聚效率低于较大的NAG颗粒。这强调了颗粒大小在团聚过程中的重要性。盐酸普萘洛尔未与SA形成团聚物，因为它们的颗粒大小和电荷相同。因此，在片剂压制前对粉末进行团聚，能够改变并控制药物从SA基质片剂中的释放速率以及片剂的抗张强度。
