Relative humidity–temperature transition boundaries for anhydrous β‐caffeine and caffeine hydrate crystalline forms

Abstract

Caffeine is a hydrate‐forming polymorphic crystalline compound that can exist in α, β, and hydrate forms. Phase transitions between hydrate and anhydrous forms of a crystalline ingredient, and related water migration, can create product quality challenges. The objective of this study was to determine the relative humidity (RH)–temperature phase boundary between anhydrous β‐caffeine and caffeine hydrate. The β‐caffeine→caffeine hydrate and caffeine hydrate→β‐caffeine RH–temperature transition boundaries were determined from 20 to 45 °C using a combination of water activity (aw) controlled solution and vapor‐mediated equilibration, moisture sorption, powder X‐ray diffraction, and Fourier‐transform infrared spectroscopy techniques. Two transition boundaries were measured: the β‐caffeine→caffeine hydrate transition boundary (0.835 ± 0.027 aw at 25 °C) was higher than the caffeine hydrate→β‐caffeine transition boundary (0.625 ± 0.003 aw at 25 °C). Moisture sorption rates for β‐caffeine, even at high RHs (>84% RH), were slow. However, caffeine hydrate rapidly dehydrated at low RHs (<30% RH) into a metastable transitional anhydrous state with a similar X‐ray diffraction pattern to metastable α‐caffeine. Exposing this dehydrated hydrate to higher RHs (>65% RH) at lower temperatures (20 to 30 °C) resulted in full restoration to a 4/5 caffeine hydrate. This transitional anhydrous state was unstable and converted to a less hygroscopic state after annealing at 50 °C and 0% RH for 1 day. It was postulated that the caffeine hydrate→β‐caffeine was the true β‐caffeine↔caffeine hydrate phase boundary and that β‐caffeine could be metastable above the caffeine hydrate→β‐caffeine transition boundary. These caffeine RH–temperature transition boundaries could be used for selecting formulation and storage conditions to maintain the desired caffeine crystalline form. Practical Application Caffeine can exist as either an anhydrous (without water) or hydrate (internalized water) crystalline state. The stability of each caffeine crystalline form is dictated by humidity (or water activity) and temperature, and these environmental stability boundaries for the caffeine crystalline forms are reported in this manuscript. Conversions between the two crystalline states can lead to deleterious effects; for example, the presence of caffeine hydrate crystals in a low water activity food (e.g., powder) could lead to the relocation of the water in caffeine to other ingredients in the food system, leading to unwanted water–solid interactions that could cause clumping and/or degradation.

From Microdroplets to Microcrystals: Tunable Caffeine Particles by Spray Flash Evaporation

“…In order to check for the presence of different polymorphs, we compared the confocal Raman and XRD spectra of samples obtained in the different process conditions (Figure ). In particular, we compared the Raman peak at ∼1650 cm –1 and the XRD peaks at 2θ = 25–27°, demonstrating the formation of anhydrous caffeine crystals in β phase − which also corresponds to the precursor phase. Because of the limited polymorphs of caffeine, the possibility of controlling polymorphism by tuning the SFE process parameter was not further explored; however, this important aspect will be investigated in the next future on more appropriate organic crystals.…”