02819nas a2200241   4500008004100000022001400041245009100055210006900146260000900215300001400224490000700238520200900245653002302254653003102277653002302308653001702331653002002348100002702368700002202395700002002417700002302437856011702460       2024                        eng d  a1543-838400aIn situ monitoring of competitive coformer exchange reaction by 1H MAS solid-state NMR0 aIn situ monitoring of competitive coformer exchange reaction by   cFEB   a1479-14890 v213 a<p>
	In a competitive coformer exchange reaction, a recent topic of interest in pharmaceutical research, the coformer in a pharmaceutical cocrystal is exchanged with another coformer that is expected to form a cocrystal that is more stable. There will be a competition between coformers to form the most stable product through the formation of hydrogen bonds. This will cause destabilization of the pharmaceutical products during processing or storage. Therefore, it is important to develop a mechanistic understanding of this transformation by monitoring each and every step of the reaction, employing a technique such as H-1 nuclear magnetic resonance (NMR). In this study, an in situ monitoring of a coformer exchange reaction is carried out by H-1 magic angle spinning (MAS) solid-state NMR (SSNMR) at a spinning frequency of 60 kHz. The changes in caffeine maleic acid cocrystals on addition of glutaric acid and caffeine glutaric cocrystals on addition of maleic acid were monitored. In all of the reactions, it has been observed that caffeine glutaric acid Form I is formed. When glutaric acid was added to 2:1 caffeine maleic acid, the formation of metastable 1:1 caffeine glutaric acid Form I was observed at the start of the experiment, indicating that the centrifugal pressure is enough for the formation. The difference in the end product of the reactions with a similar reaction pathway of 1:1 and 2:1 reactant stoichiometry indicates that a complete replacement of maleic acid has occurred only in the 1:1 stoichiometry of the reactants. The polymorphic transition of caffeine glutaric acid Form II to Form I at higher temperatures was a crucial reason that triggered the exchange of glutaric acid with maleic acid in the reaction of caffeine glutaric acid and maleic acid. Our results are novel since the new reaction pathways in competitive coformer exchange reactions enabled understanding the remarkable role of stoichiometry, polymorphism, temperature, and centrifugal pressure.</p>
10acaffeine cocrystal10acoformer exchange reaction10ain situ monitoring10apolymorphism10aSolid-state NMR1 aHareendran, Chaithanya1 aAlsirawan, Bashir1 aParadkar, Anant1 aAjithkumar, T., G.  uhttps://library.ncl.res.in/content/situ-monitoring-competitive-coformer-exchange-reaction-1h-mas-solid-state-nmr02106nas a2200229   4500008004100000022001400041245008600055210006900141260000900210300001400219490000700233520136100240653001601601653001701617653002701634653001901661653001501680100002701695700002601722700002301748856010501771       2024                        eng d  a1543-838400aInsights into the structure of sucralfate by advanced solid- and liquid-state NMR0 aInsights into the structure of sucralfate by advanced solid and   cFEB   a1390-14010 v213 a<p>
	Sucralfate, which is a sucrose octasulfate aluminum complex, is an active pharmaceutical ingredient (API) falling in the category of cytoprotective agents which are very effective for gastric and duodenal ulcers. On interaction with stomach acid, it ionizes into aluminum and sucrose octasulfate ions to form a protective layer over the ulcerated region inhibiting further attack from acid. The mechanism of action of sucralfate in the context of its structure is not well understood. Considering that at least two forms of this API are available in the market, there are no reports on the various forms of sucralfate and differences in their pharmacological action. We characterized the two forms of sucralfate using multinuclear, multidimensional solid-state NMR, and the results show significant structural differences between them arising from variation in the aluminum environment and the level of hydration. The impact of structural differences on pharmacological action was examined by studying acid-induced Al release by Al-27 liquid-state NMR. The sucralfate, European pharmaceutical standard, Form I, undergoes faster disruption in acid compared to Form II. The difference is explained on the basis of structural differences in the two forms which gives significant insights into the action of sucralfate in relation to its structure.</p>
10a(27)AlMQMAS10aH-1-H-1 DQSQ10apharmacological action10asolid-stateNMR10asucralfate1 aHareendran, Chaithanya1 aRavindranathan, Sapna1 aAjithkumar, T., G.  uhttps://library.ncl.res.in/content/insights-structure-sucralfate-advanced-solid-and-liquid-state-nmr