Amorphization of Thiamine Chloride Hydrochloride: Effects of Physical State and Polymer Type on the Chemical Stability of Thiamine in Solid Dispersions

Abstract

Thiamine is an essential micronutrient, but delivery of the vitamin in supplements or foods is challenging because it is unstable under heat, alkaline pH, and processing/storage conditions. Although distributed as a crystalline ingredient, thiamine chloride hydrochloride (TClHCl) likely exists in the amorphous state, specifically in supplements. Amorphous solids are generally less chemically stable than their crystalline counterparts, which is an unexplored area related to thiamine delivery. The objective of this study was to document thiamine degradation in the amorphous state. TClHCl:polymer dispersions were prepared by lyophilizing solutions containing TClHCl and amorphous polymers (pectin and PVP (poly[vinylpyrrolidone])). Samples were stored in controlled temperature (30–60 °C) and relative humidity (11%) environments for 8 weeks and monitored periodically by X-ray diffraction (to document physical state) and HPLC (to quantify degradation). Moisture sorption, glass transition temperature (Tg), intermolecular interactions, and pH were also determined. Thiamine was more labile in the amorphous state than the crystalline state and when present in lower proportions in amorphous polymer dispersions, despite increasing Tg values. Thiamine was more stable in pectin dispersions than PVP dispersions, attributed to differences in presence and extent of intermolecular interactions between TClHCl and pectin. The results of this study can be used to control thiamine degradation in food products and supplements to improve thiamine delivery and decrease rate of deficiency.

Amorphization of Thiamine Mononitrate: A Study of Crystallization Inhibition and Chemical Stability of Thiamine in Thiamine Mononitrate Amorphous Solid Dispersions

“…The physical state (amorphous vs. crystalline) of a compound is known to influence its chemical stability. Amorphous materials, including thiamine, are generally less chemically stable than their crystalline counterparts [ 10 , 16 ]. In the current study, the chemical stability of thiamine in the crystalline state was measured over an 8-week period of storage in different environments (at 11% RH and 30–60 °C and 75% RH and 25–40 °C) in three sample types: (1) pure crystalline TMN (control); (2) physical mixtures containing 5% crystalline TMN and 95% PEC; and (3) physical mixtures containing 5% crystalline TMN and 95% PVP.…”

“…A study of TClHCl in solid dispersions found that polymers (such as pectin (PEC)) that could form the most extensive hydrogen bonding and/or ionic interactions with TClHCl were the most effective crystallization inhibitors, extending the physical stability of TClHCl in the amorphous state better than polymers (such as polyvinylpyrrolidone (PVP)) with fewer intermolecular interactions with the vitamin form [ 8 ]. Amorphous forms of ingredients tend to be more chemically labile than their crystalline counterparts [ 9 ], which was found to be true for the thiamine in the TClHCl solid dispersions; however, differences in the chemical stability of thiamine in the amorphous state in the presence of different polymers were also found [ 10 ]. In the amorphous TClHCl solid dispersions, thiamine was more chemically stable in the presence of pectin compared to PVP, which can be attributed to the increased intermolecular interactions between pectin and thiamine and the more acidic nature of pectin [ 10 ].…”

“…Amorphous forms of ingredients tend to be more chemically labile than their crystalline counterparts [ 9 ], which was found to be true for the thiamine in the TClHCl solid dispersions; however, differences in the chemical stability of thiamine in the amorphous state in the presence of different polymers were also found [ 10 ]. In the amorphous TClHCl solid dispersions, thiamine was more chemically stable in the presence of pectin compared to PVP, which can be attributed to the increased intermolecular interactions between pectin and thiamine and the more acidic nature of pectin [ 10 ].…”

“…The interesting insights into the physical and chemical stability of thiamine in amorphous TClHCl solid dispersions developed in previous work [ 8 , 10 ] are extended here to the ingredient form of thiamine (TMN) that is more often used in low and intermediate moisture foods and dietary supplements, wherein crystallization and degradation in different solid states are highly relevant. Although TMN is potentially found in its amorphous form in food and dietary supplement products, there has been no study conducted to investigate its physical and chemical stability in the amorphous form.…”

“…The effects of counterion and pH differences on the stability of thiamine in the TClHCl versus TMN solid dispersions were of interest. Therefore, the objectives of this study were: (1) to investigate physical and chemical stability of amorphous TMN in solid dispersions made using PVP and pectin (which were selected based on their T g , hydrogen bonding ability, molecular structures, and hygroscopicity); (2) to compare thiamine degradation in the amorphous and crystalline state; (3) to determine the factors causing chemical instability of thiamine in amorphous form; and (4) to compare thiamine stability in polymer dispersions containing TMN to previous reports of those containing TClHCl [ 8 , 10 ].…”