Qiu Zhihui, Stowell Joseph G, Cao Wenjin, Morris Kenneth R, Byrn Stephen R, Carvajal M Teresa
Schering-Plough Research Institute, 2000 Galloping Hill Road, K-11-2-J4, Kenilworth, New Jersey 07076, USA.
J Pharm Sci. 2005 Nov;94(11):2568-80. doi: 10.1002/jps.20448.
The effects of milling and compression on the solid-state Maillard reaction between metoclopramide hydrochloride and lactose were investigated. Anhydrous metoclopramide hydrochloride was milled for various times, and then mixed with amorphous lactose. The mixtures were stored at 105 degrees C and 0% RH. The reactivity of metoclopramide hydrochloride towards the Maillard reaction increased with milling time, as the result of increased surface area, formation of amorphous content, and creation of defects. Metoclopramide hydrochloride anhydrate and lactose were mixed and the mixtures were compressed into tablets under pressure varied from 70 to 350 MPa. Both tablets and mixtures were stored at 105 degrees C and 0% RH for 9 days. For all three types of lactose used, spray-dried anhydrous lactose, spray-dried lactose monohydrate, and amorphous lactose, tablets exhibited higher reaction rate toward the Maillard reaction than the powder mixtures. Tablets containing metoclopramide hydrochloride and amorphous lactose prepared at higher pressure showed higher reaction rates than those prepared at lower pressure. This is due to increased contact between reactants and an increased amount of water retained in the tablets.
研究了研磨和压片对盐酸甲氧氯普胺与乳糖之间固态美拉德反应的影响。将无水盐酸甲氧氯普胺研磨不同时间，然后与无定形乳糖混合。混合物在105℃和0%相对湿度下储存。由于表面积增加、无定形成分形成以及缺陷产生，盐酸甲氧氯普胺对美拉德反应的反应活性随研磨时间增加。将无水盐酸甲氧氯普胺和乳糖混合，并在70至350MPa的压力下将混合物压制成片剂。片剂和混合物均在105℃和0%相对湿度下储存9天。对于所使用的三种乳糖，即喷雾干燥无水乳糖、喷雾干燥一水乳糖和无定形乳糖，片剂对美拉德反应的反应速率高于粉末混合物。在较高压力下制备的含盐酸甲氧氯普胺和无定形乳糖的片剂比在较低压力下制备的片剂显示出更高的反应速率。这是由于反应物之间的接触增加以及片剂中保留的水量增加。
