The Development of a Novel Pharmaceutical Formulation of D-Tagatose for Spray-Drying

Purpose: D-tagatose is an alternative sweetener with superior properties for reducing overall sugar absorption, which is especially important in the diabetic population. Large-scale production of D-tagatose remains costly, thereby limiting its commercialization. Introducing the unit operation of spray-drying may reduce some of these costs. However, D-tagatose is challenging to spray-dry due to its hydrophilic nature and low glass transition temperature (T_g). An appropriate spray-drying feed solution may offer an alternative approach if the material produced is glassy in nature, thus avoiding stickiness issues associated with T_gs less than the outlet temperature of the spray-dryer. Proof-of-concept formulations and processing conditions are presented in this study. Methods: D-tagatose was formulated with several excipients and screened for a sufficiently high T_g as characterized by differential scanning calorimetry (DSC). The spray-dry formulations were further characterized using attenuated total reflectance Fourier transform infrared spectrometry (ATR-FTIR), powder X-ray diffraction (PXRD), and scanning electron microscopy (SEM), and several viable options were identified. Results: D-tagatose formulated with HPMCAS and K90 both raised the T_g mix (Tgmix) to within the processing range of spray-drying. These formulations were found to be sufficiently soluble in acetone/water cosolvent systems allowing for the production of processable powder. Specifically, SEM results confirm that both D-tagatose-HPMCAS and D-tagatose-K90 formulations result in particle formation using a small-scale dryer. Large-scale spray-drying is expected to allow for a greater processing range in comparison to small scale, suggesting that this approach will help commercialization. ATR-FTIR and PXRD results suggested that spray-dried D-tagatose-K90 composites lacked crystallinity, unlike the D-tagatose-HPMCAS composites. Conclusions: The addition of functional excipients allowed D-tagatose composites to be harvested using a typical laboratory-scale spray-dryer equipped with a bi-fluid nozzle. D-tagatose-K90 lacks crystallinity, while crystallinity is present in D-tagatose-HPMCAS composites. Crystallinity may not be a critical factor (depending on the future application) given the high aqueous solubility and high loading of the sugar. Both composites retained a sweet taste, suggesting that this spray-drying method may be worth further development. Other polymers with high T_g may be feasible as composites as well—as long as the amorphous phase or the residual amorphous phase has a T_g greater than, or about equal to, the outlet temperature of the spray-dryer.