Solid pharmaceuticals: Analysis and identification by solid state carbon-13 NMR

This thesis describes two studies of solid pharmaceuticals by $\sp{13}$C solid-state NMR. The first study involved measuring the methyl activation energies of four different 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors and then comparing the NMR data to temperature factor data obtained from single crystal x-ray diffraction. X-ray data revealed that the butanoate side-chain common to all four compounds is extremely disordered. The disorder was greater in the two compounds containing two 2$\sp\prime$-methyl substituents in the side-chain. The activation energy values showed a general trend; 4$\sp\prime < 2\sp\prime$-methyl $<$ 3-methyl $<$ 7-methyl. The results indicated that there is some correlation between the NMR data and the x-ray data. Secondly, the study of three different tableted dosage forms by $\sp{13}$C solid-state NMR is described. The drugs studied were prednisolone, enalapril maleate, and drug X (proprietary information). These studies showed that $\sp{13}$C solid-state NMR is useful for (1) the determination of polymorphs within the tableted forms and (2) that the interrupted decoupling pulse sequence is useful in enhancing the signals due to drugs while eliminating the excipient peaks. Elimination of excipient peaks allowed for the observation of $\sim$5% drug in a tablet. These experiments illustrate that solid-state $\sp{13}$C NMR is a powerful analytical technique for pharmaceutical solids in tableted dosage forms.