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

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Abstract

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 (Tg). 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 Tgs 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 Tg 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 Tg mix (\( {T}_{g_{\mathrm{mix}}} \)) 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 Tg may be feasible as composites as well—as long as the amorphous phase or the residual amorphous phase has a Tg greater than, or about equal to, the outlet temperature of the spray-dryer.

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Funding

The authors would like to acknowledge the Department of Pharmaceutical Sciences at the University of Kentucky for financial support of this project. The authors would also like to acknowledge the University of Kentucky Electron Microscopy Center, along with their funding resources.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, University of Kentucky, Lexington, KY, USA

    Heather R. Campbell, Fahd M. Alsharif, Patrick J. Marsac & Robert A. Lodder

  2. Department of Pharmaceutics and Industrial Pharmacy, College of Pharmacy, Al-Azhar University, Assiut, Egypt

    Fahd M. Alsharif

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  1. Heather R. Campbell
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  4. Robert A. Lodder
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Correspondence to Robert A. Lodder.

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Campbell, H.R., Alsharif, F.M., Marsac, P.J. et al. The Development of a Novel Pharmaceutical Formulation of D-Tagatose for Spray-Drying. J Pharm Innov 17, 194–206 (2022). https://doi.org/10.1007/s12247-020-09507-4

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