Solid-state interaction of magnesium oxide and ibuprofen to form a salt.
During formulation development work involving ibuprofen, a solid-state interaction between MgO and ibuprofen was observed. In this study the interaction of MgO and ibuprofen was investigated for 1:1 and 2:1 M mixtures of ibuprofen and MgO, which had been stored at 55 degrees C, using the differential scanning calorimetric (DSC), thermogravic analysis (TGA), and multiple internal reflectance infrared (MIR) techniques. Evidence for the reaction was the disappearance of the melting endotherm at 79 degrees C and appearance of a new endotherm at 161 degrees C after less than 1 day of storage at 55 degrees C and, also, the change in the physical appearance of the mixtures. Comparison of the DSC, TGA, and MIR data for the reacted ibuprofen and MgO mixtures and synthetic Mg(ibuprofen)2 indicated that MgO and ibuprofen react to form the Mg salt of ibuprofen. The interaction of ibuprofen and MgO was also studied at 30 and 40 degrees C, using 1:1 M mixtures. At 30 degrees C no significant interaction was observed for up to 80 days; however, at 40 degrees C a reaction was evident on day 1. NaHCO3, K2CO3 1.5H2O, CaO, and Mg(OH)2 also showed solid-state reactions with ibuprofen. MgCl2 and Al(OH)3 did not show this reaction.
Kararli
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TT
G. D. Searle & Co., Product Development, Skokie, Illinois 60077.
Needham
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TE
Seul
C J
CJ
Finnegan
P M
PM
D002152:Calorimetry, Differential Scanning; D055598:Chemical Phenomena; D002621:Chemistry; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D007052:Ibuprofen / Q000032:analysis*; D008277:Magnesium Oxide / Q000032:analysis*; D013055:Spectrophotometry, Infrared; D013056:Spectrophotometry, Ultraviolet
D008277:Magnesium Oxide; D007052:Ibuprofen