Effect of milling and compression on the solid-state Maillard reaction

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. (c) 2005 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 94:2568-2580, 2005.