Analysis of the Transformation of Caffeine in Poly Acrylic Acid

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Daniel P. Brooks


Understanding the inhibitory affects of polymer exc1p1ents on the hydration of active pharmaceutical ingredients (API) during wet granulation may significantly influence the current procedure of industrial tablet production by reducing unwanted transformations. The anhydrate to hydrate transformation of API crystals often influences the bioavailability of a drug due to differences in solubility compared to the anhydrous crystals. This unwanted transformation may be inhibited through the use of a specific polymer as an excipient. The hydrate transformation of caffeine was analyzed in a high sheer aqueous slurry. Small amounts of polymer excipients were added to the slurries to determine the effects on the transformation. The caffeine transformation was monitored using in-line Raman spectroscopy via an immersion probe at regular intervals. A calibration was used to construct the kinetic transformation profiles by quantifying the relative amounts of hydrate and anhydrate caffeine as determined by the ratio of specific peak intensities in the Raman spectra. The results showed that poly acrylic acid (PAA) was effective at inhibiting the transformation at concentrations as low as 0.0 I mg/mL and showed complete inhibition for at least 400 min at a PAA concentration of 2.0mg/mL. The results from other polymers including hydroxypropyl methyl cellulose (HPMC), poly vinyl pyrrolidone (PVP) and poly ethylene oxide showed little to no inhibition at concentrations of 2.0mg/rnL. In addition, seeding experiments were performed to determine if nucleation or crystal growth inhibition was the source of overall inhibition. Analysis of kinetic profiles showed PAA inhibited both the nucleation of hydrate and the growth of caffeine hydrate crystals.


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