Characterization of hydrate transformation and dissolution of bicomponent tablets using near-infrared spectroscopy

The purpose of this research was to expand the applications of near-infrared spectroscopy (NIBS) in the pharmaceutical industry. NIBS was used as the key analytical method to perform qualitative and quantitative analysis of hydrate transformation and dissolution of bicomponent tablets.; NIRS was demonstrated to be a feasible analytical technique to quantify the weight percentage of each component on the surface of a binary mixture tablet using alpha-D-glucose and glutamine as model compounds. The failure of the developed method to predict the glucose/glutamine concentration on the tablet surface in water was identified as due to the transformation of anhydrous glucose to glucose monohydrate. A dynamic transformation process of anhydrous glucose to glucose monohydrate was observed and quantified using a NIRS method. The NIR bands of glucose monohydrate were identified by comparing the mid-infrared spectra of anhydrous glucose and glucose monohydrate. A kinetic model of the recrystallization data was developed and the effect of compression force was also studied. A similar phenomenon was observed for the anhydrous caffeine and theophylline tablets in water. The observed hydrate transformation was confirmed by the dissolution test.; Based on the success of single-component tablets, the dissolution behavior of a binary mixture tablet was investigated. Intrinsic dissolution test of a tablet consisting of a 1:1 (w/w) mixture of sulfanilamide and sulfapyridine was performed and the NIR spectra of the dissolving tablet surface were acquired. The spectra clearly indicated the constant decrease of the sulfanilamide concentration (the more water-soluble drug) at the tablet surface compared to sulfapyridine. These results were further correlated to the dissolution data. A dissolution model was developed based on the assumption that the dissolution of the more water-soluble component in a bicomponent tablet can be modeled as a hybrid of diffusion from both solid matrix and solid-liquid interface; the less water-soluble drug diffuses from solid-liquid interface only. It was also found that despite the initial drug loading, the surface composition for a certain bicomponent system approaches a constant ratio at steady state and it is primarily controlled by the solubility difference between these two components.