Potential of Solid-state NMR and SEM in Characterization of Tablets of Ibuprofen

Small differences of active pharmaceutical ingredient and excipients directly in a dosage form have been assessed on different brands of tablets of ibuprofen by a combined use of solid-state NMR and SEM offering information at both atomistic and microscopic levels of resolution. NMR spectra of pure ibuprofen and its sodium salt were measured and the chemical shifts of individual signals were used to characterize the polymorphic state of ibuprofen within tablets from five different commercial providers. Proton solid-state NMR spectra showed that ibuprofen is present in acidic form in all tablet samples and revealed different contents of bound water within tablets. Carbon NMR spectra confirmed the protonation state and furthermore ascertained the presence of the same polymorph of ibuprofen in all tablets. A single molecule of API is present in the crystallographic asymmetric unit. Solidstate NMR proved its potential in identifying small differences between tablet samples, which were attributed to different excipients whose type and quantity varied among the studied tablets. Different crystal habits have been observed for ibuprofen within tablets using scanning electron micrographs which also show variations in structure porosity of tablet samples. Keywords: Analysis, excipients, polymorphism, solid dosage form, solid-state NMR, water in solids.