Insoluble Salt of Memantine with a Unique Fluorescence Phenomenon

Alzheimer's disease is a chronic disease, and the long-term treatment of chronic diseases has always been a concern. Memantine (Mem) is approved by the US Food and Drug Administration for the treatment of moderate to severe Alzheimer's disease. In this study, reactions of memantine (Mem) with pamoic acid (Pam) were carried out to form insoluble salts (Mem-Pam). Four polymorphic forms (Forms I-IV) of Mem-Pam were successfully obtained through polymorphic screening, which were systematically characterized by X-ray powder diffraction (PXRD), thermal analysis (TGA and DSC), single-crystal X-ray diffraction (SXRD), and solid-state fluorescence. Compared with the hydrochloride form, the dissolution and release rates of these four forms are lower. The presence of pamoic acid reduces the release rate of memantine and makes it possible to achieve a sustained release of the drug. Interestingly, because of the presence of memantine, each polymorphic solid crystal of Mem-Pam has unique fluorescence emission. Therefore, memantine and pamoic acid have a synergistic effect on the fluorescence performance and can be expected to be used for real-time monitoring in continuous and controlled release drug delivery systems. In addition, the polymorphic solid crystals also exhibit reversible mechanochromic luminescence under the fumigation of acetonitrile vapor, which has a guiding role in the fluorescence design and synthesis of Pam substances and is expected to be used for information security, visual inspection of organic substances, etc.