Formulations of hygroscopic materials

Abstract

The present disclosure provides compositions comprising a hygroscopic material and a desiccant material, optionally wherein the hygroscopic material is choline chloride, and processes for preparing said compositions. Also provided are uses of solid compositions disclosed herein in nutritional formulations, such as infant formulas and dietary supplements.

Description

FORMULATIONS OF HYGROSCOPIC MATERIALS Technical Field

[0001] The present disclosure broadly relates to compositions comprising a hygroscopic material, processes for producing said compositions, and to methods of improving powder flowability of a material. Background of the Disclosure

[0002] Choline is an essential nutrient with a variety of functions. It is a precursor to acetylcholine, a neurotransmitter essential for memory-related function. During pregnancy, choline is passed from mother to growing baby helps to prevent neural tube defects and may help improve the child's ability to focus and process information later in life; in early childhood and beyond, choline continues to boost the brain's ability to grow and function well and helps the brain process and store memories. Choline also inhibits liver enlargement and helps cell membrane signalling; it plays a role in the process that helps metabolise and move fat out of the liver, keeping it healthy and functioning properly to filter nutrients and convert food into energy. Further, choline reduces the amount of homocysteine in the blood (high levels of which are associated with increased risk for heart disease), and promotes and regulates metabolism for increased energy, whilst also sending messages from the brain to muscles for improved movement and endurance.

[0003] Choline finds use in the treatment of mental health disorders, including depression and anxiety, and aids in the prevention of chronic diseases, age-related memory problems and heart problems.

[0004] Given its importance, widespread choline deficiency is a matter of public health concern. In Australia, the recommended daily intake (RDI) of choline for pregnant women aged 19 - 50 years is 440mg / day, and the RDI for lactating women aged 19-50 years is 550mg / day. The majority of pregnant and lactating women do not meet these RDIs.

[0005] There is high demand for choline for its use in infant formula, in which choline is included at levels such as 20-100 mg / 100kcal (China, 0-12 months) or 23-50 mg / 100kcal (European Union, 0-12 months). For requirements at various stages of life, choline is commonly fortified into nutritional formulas, foods, beverages and dietary supplements.

[0006] Commercially available choline sources include choline bitartrate, choline chloride and choline dihydrogen citrate. However, choline dihydrogen citrate is expensive, is less readily available than alternative sources, and contains only about 35% choline, whilst choline bitartrate has a relatively low choline content (about 37%) and is hygroscopic, making its handling difficult. Choline chloride, whilst generally cheaper and containing a higher amount of choline (from about 70% to about 80%), is extremely hygroscopic and will readily absorb atmospheric moisture leading to unwanted caking and clumping, difficulties in use and application limitations.

[0007] There remains a need for forms of choline with a sufficiently high choline content, which may be easily handled and processed for incorporation into nutritional products. Summary of the Disclosure

[0008] The present disclosure is predicated on the inventors’ unexpected determination that hydrating a hygroscopic material and a desiccant material, such as choline chloride and a desiccant salt, and subsequently drying, such as by way of spray-drying, leads to a powdered composition which is less likely to form agglomerates (e.g. lumps or a cake). This improved powder flowability enables further handling and processing for use, for example, in nutritional formulations such as infant formula.

[0009] A first aspect of the disclosure provides a solid composition comprising a hygroscopic material and a desiccant material.

[0010] In particular embodiments, the solid composition is a powder. In particular embodiments, the solid composition is a dried composition, optionally a spray-dried composition.

[0011] Optionally, the hygroscopic material is a source of choline. The source of choline may be a choline salt, optionally selected from choline chloride, choline bitartrate and choline dihydrogen citrate. In a particular embodiment, the choline salt is choline chloride.

[0012] Optionally, the desiccant material is a salt. The desiccant material may be selected from a calcium salt, a copper salt, a magnesium salt, a potassium salt and a sodium salt, and hydrates thereof. The desiccant material may be selected from, calcium oxide, calcium sulphate, copper sulphate, magnesium chloride, magnesium sulphate, potassium carbonate, potassium hydroxide, potassium chloride, potassium fluoride, sodium chloride, sodium hydroxide, sodium sulphate, disodium hydrogen phosphate, calcium bromide, iron chloride, sodium thiosulphate and hydrates thereof, optionally selected from selected from sodium carbonate, potassium chloride and magnesium sulphate. In a particular embodiment, the desiccant material is magnesium sulphate heptahydrate or magnesium sulphate monohydrate.

[0013] In exemplary embodiments, the ratio of the hygroscopic material to the desiccant material in the composition is from about 1:1 to about 30:1. In a particular embodiment, the ratio of the hygroscopic material to the desiccant material in the composition is at least about 0.9:0.1. In a particular embodiment, the ratio of the hygroscopic material to the desiccant material in the composition is about 0.96:0.04. In a particular embodiment, the ratio of the hygroscopic material to the desiccant material in the composition is about 0.6:0.4.

[0014] In exemplary embodiments, the solid composition comprises at least about 50% choline. In some embodiments, the composition comprises up to about 69% choline. In some embodiments, the composition comprises from about 40 to about 60 % choline. In some embodiments, the composition comprises about 50% choline.

[0015] In some embodiments, the composition further comprises a processing aid. The processing aid may comprise, for example, silicon dioxide and / or tricalcium phosphate. In some embodiments, silicon dioxide is present in the composition in an amount of up to about 1% by weight. In some embodiments, tricalcium phosphate is present in the composition in an amount of up to about 10% by weight.

[0016] A second aspect of the disclosure provides a process for preparing a solid composition comprising a hygroscopic material, comprising: a) providing a liquid composition of a hygroscopic material and a desiccant material; and b) drying the liquid composition of step a) to provide a solid composition.

[0017] In an exemplary embodiment, the solid composition is a spray-dried composition and step b) comprises spray-drying the liquid composition of step a). In some embodiments, a processing aid, such as silicon dioxide and / or tricalcium phosphate, is added during step b).

[0018] In a further exemplary embodiment, the solid composition is a composition according to the first aspect. The liquid composition may be a solution of a hygroscopic material and a desiccant material.

[0019] In an exemplary embodiment, the liquid composition of step a) comprises at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, at least about 95%, or at least about 99% of the hygroscopic material based on the combined weight of the hygroscopic material and the desiccant material in the liquid composition. In an exemplary embodiment, the hygroscopic material is a choline salt and the liquid composition of step a) comprises at least about 40%, at least about 50%, at least about 60% or at least about 70% choline based on the combined weight of the hygroscopic material and the desiccant material in the liquid composition.

[0020] A third aspect of the disclosure provides a solid composition obtained by a process of the second aspect.

[0021] A fourth aspect of the disclosure provides a method of improving powder flowability of a hygroscopic material, comprising: a) providing a liquid composition of said hygroscopic material and a desiccant material; and b) drying the liquid composition of step a) to provide a solid composition, thereby improving powder flowability of the hygroscopic material.

[0022] A fifth aspect of the disclosure provides a liquid composition comprising a hygroscopic material and a desiccant material. The liquid composition may be a solution of a hygroscopic material and a desiccant material.

[0023] The liquid composition may comprise at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, at least about 95% or at least about 99% of the hygroscopic material based on the combined weight of the hygroscopic material and the desiccant material in the liquid composition. In an embodiment, the hygroscopic material is a choline salt and the composition comprises at least about 40%, at least about 50%, at least about 60% or at least about 70% choline based on the combined weight of the hygroscopic material and the desiccant material in the liquid composition.

[0024] In a particular embodiment, the hygroscopic material is choline chloride. In an exemplary embodiment, the desiccant material is selected from a calcium salt, a copper salt, a magnesium salt, a potassium salt and a sodium salt, and hydrates thereof. The desiccant material may be, for example, magnesium sulphate, optionally magnesium sulphate heptahydrate or magnesium sulphate monohydrate.

[0025] A further aspect of the disclosure provides a nutritional formulation comprising a solid composition of the first or third aspects. In exemplary embodiment, the nutritional formulation is an infant or other nutritional formula, or a dietary supplement.

[0026] Another aspect of the disclosure provides for a use of the solid composition of the first and third aspects for preparing a nutritional formulation, food, beverage, or a dietary supplement. Brief Description of the Figures

[0027] Exemplary embodiments of the present disclosure are described herein, by way of non-limiting example only, with reference to the following drawings.

[0028] Figure 1. Compositional analysis of powder using X-ray diffraction. Stacked XRD plots (y-axis: intensity (a.u.); x-axis: 2θ (°)) of 45% choline chloride with magnesium sulphate (pink; top trace) and a 73% choline control sample (black; bottom trace).

[0029] Figure 2. Moisture absorption isotherms for test compositions comprising 50% choline chloride and magnesium sulphate as desiccant (purple; upper trace) and 60% choline chloride and magnesium sulphate as desiccant (green; middle trace), compared to a control composition containing 73.1% choline chloride and no desiccant salt (blue; lower trace). Detailed Description

[0030] Throughout this specification, unless the context requires otherwise, the word "comprise", or variations such as "comprises" or" comprising", will be understood to imply the inclusion of a stated step or element or integer or group of steps or elements or integers, but not the exclusion of any other step or element or integer or group of elements or integers. Thus, in the context of this specification, the term "comprising" means "including principally, but not necessarily solely".

[0031] In the context of this specification, the term "about" is understood to refer to a range of numbers that a person of skill in the art would consider equivalent to the recited value in the context of achieving the same function or result.

[0032] In the context of this specification, the terms "a" and "an" refer to one or to more than one (i.e. to at least one) of the grammatical object of the article. By way of example, "an element" means one element or more than one element.

[0033] As used therein, the term “hygroscopic material” means a substance or compound, or mixture of substances and / or compounds, which will readily absorb moisture from the surrounding environment or will otherwise be altered or degraded from its intended use by the presence of moisture in the surrounding environment. “Hygroscopic materials” include those materials that gain greater than about 2% by weight after exposure to about 66% relative humidity, at room temperature for about 24 hours. The material may, for example, gain greater than about 5% by weight, or about 10% by weight, or about 15% by weight, after exposure to 66% relative humidity, at room temperature for 24 hours.

[0034] As used herein, the term “choline” refers to 2-hydroxy-N,N,N-trimethylethan-1-aminium (also referred to as 2-hydroxyethyl(trimethyl)azanium), a quaternary ammonium cation. It will be appreciated that the choline component of a choline-containing compound or composition, for example a choline salt or composition as described herein, may be expressed on a mg / g basis. For example, a composition of the present invention may contain up to about 68% choline (i.e. up to about 680 mg of choline per 1.00 g of the composition), for example about 50% choline (i.e. about 500 mg of choline per 1.00 g of the composition).

[0035] The present invention is predicated on the inventors' surprising determination that drying, especially spray-drying, a hydrated mixture of a hygroscopic material, such as choline chloride, and a desiccant material, such as magnesium sulphate heptahydrate, produces a powder that is less likely to form agglomerates (i.e. form lumps, form a cake, etc.), even in the absence of further spray coating. This improved powder flowability facilitates the handling and further processing of the hygroscopic product, for example for inclusion in nutritional products such as infant formula.

[0036] Accordingly, particular embodiments of the present disclosure provide a solid composition comprising a hygroscopic material and a desiccant material. In particular embodiments the hygroscopic material is choline chloride and the desiccant material is magnesium sulphate.

[0037] In particular embodiments, the solid composition is a powder. In one embodiment, the composition is a free-flowing powder. In alternative embodiments the composition may be in the form of granules.

[0038] In particular embodiments, the composition is a spray-dried composition. A spray-dried composition is typically prepared by spray-drying a liquid composition, for example a solution of a hygroscopic material and a desiccant material, such as a hygroscopic salt and a desiccant salt. In some embodiments, the liquid composition may be an emulsion or suspension. Spray-drying typically produces a powdered product and, accordingly, in some embodiments, the composition is a spray-dried powder.

[0039] In some alternative embodiments, a liquid composition as described above is dried by means other than spray-drying, for example by way of a fluidised bed or ribbon dryer. Alternative suitable drying means will be readily identified by a person skilled in theart. Depending on the drying means to be employed and the moisture content of the materials in the composition, the composition may be first subject to centrifugation.

[0040] As used herein, a "solid composition" is to be understood as referring to solid forms, such as powders or granules, which comprise both the hygroscopic material and the desiccant material within a single powder particle or granule, in contrast to mere mixtures comprising a solid hygroscopic material mixed with a separate solid desiccant material. For example, a solid composition may be prepared by spray-drying a hydrated mixture or solution comprising both the hygroscopic material and the desiccant material, in contrast to mere mixtures of a spray-dried hygroscopic material with a separately spray-dried desiccant material.

[0041] In some embodiments the composition, especially a powder, has a mean particle size up to about 1000 ^m, for example up to about 700 ^m , for example up to about 500 ^m , for example up to about 400 ^m, for example up to about 300 ^m, preferably to about 200 ^m. In some embodiments, the composition has a mean particle size of at least 10^m, for example at least 20^m, for example at least 30^m, for example at least 40^m, for example at least 50^m, for example at least 60^m, for example at least 70^m, for example at least 80^m, for example at least 90^m, for example at least 100 ^m, for example at least 110 ^m, for example at least 120 ^m, for example at least 130 ^m, for example at least 140 ^m, for example at least 150 ^m, for example at least 160 ^m, for example at least 170 ^m, for example at least 180 ^m, for example at least 190 ^m. In some embodiments, the composition has a mean particle size between about 10 ^m and 1000 ^m, for example between about 50 ^m and about 500 ^m, for example between about 100 ^m and about 400 ^m, for example about between about 140 ^m and about 400 ^m, for example between about 100^^m and about 200 ^m.

[0042] In some exemplary embodiments, the solid composition has a moisture content below about 5% by weight, for example below about 4% by weight, for example below about 3.5% by weight, for example below about 3% by weight, for example below about 2.5% by weight, for example below about 2% by weight. In some preferred embodiments, the solid composition has a moisture content below about 2% by weight.

[0043] Moisture content may be measured by determining percent loss of weight of the composition upon drying using means and methodologies that will be well known to those skilled in the art, for example the gravimetric method. By way of example, a prescribed amount (weight) of sample may be dried at a specified temperature over a specified period of time, e.g. about 110-120°C for a minimum of about 2 h. The difference in weight (before and after drying) is calculated as the percentage loss on drying.

[0044] The hygroscopic material for use according to the present invention may be any hygroscopic material suitable for inclusion in a composition, for example a nutritional consumption or supplement for human or animal consumption, the hygroscopic material being a substance or compound, or mixture of substances and / or compounds, that, as defined above, readily absorbs moisture or water from the surrounding environment and / or whose activity or usefulness will be diminished in such an environment. Accordingly, in particular embodiments the hygroscopic material is one that has some nutritional or medicinal use. The material may be, for example, a nutrient, vitamin, prebiotic, enzyme or other suitable drug. The material may be a carbohydrate, protein, glycoprotein, polypeptide, peptide, amino acid or amino acid derivative. Exemplary vitamins and nutrients include riboflavin, nicotinic acid, nicotinic acid amide, calcium pantothenate, choline pantothenate, pyridoxine hydrochloride, choline chloride, cyanocobalamin, biotin, folic acid and p-aminobenzoic acid. Exemplary amino acids include methionine, lysine, threonine, leucine, isoleucine, tryptophan, phenylalanine, valine and glycine. Exemplary amino acid derivatives include N- acylamino acids, such as N-stearoylmethionine, N-oleoylmethionine, the calcium salt of N- hydroxymethylmethionine, lysine hydrochloride, methionine hydroxy analogues and sodium glutamate.

[0045] In exemplary embodiments the hygroscopic material may be a source of a nutritional ingredient. In some embodiments of the present invention, the hygroscopic material is a source of choline, for example a choline salt. Choline is an essential nutrient and use of sources of choline such as choline salts as the hygroscopic material facilitate the inclusion of choline in, for example, nutritional formulations such as infant formula. In some embodiments of the present invention, the choline salt is choline chloride, choline bitartrate or choline dihydrogen citrate. In some particular embodiments, the choline salt ischoline chloride or choline bitartrate. In particularly preferred embodiments, the choline salt is choline chloride.

[0046] Hygroscopicity of the hygroscopic material or of a composition comprising the hygroscopic material, including compositions of the present invention, may be determined by any means known to those skilled in the art. For example, hygroscopicity may be assessed by visual assessment of a material, composition or product left exposed to atmospheric conditions over a period of time, to identify onset of moisture absorption or agglomeration. Hygroscopicity may also be assessed by examining moisture sorption isotherms, which measures the water activity over varying relative humidities at constant temperature. By way of example, water activity (aW) of solid compositions of the present invention may be less than or about 0.5, less than or about 0.4, less than or about 0.3, less than or about 0.2, or less than or about 0.1. For example, water activity may be between about 0.1 and 0.2, such as 0.1, 0.11, 0.12, 0.13, 0.14, 0.15, 0.16, 0.17, 0.19, 0.2, or 0.21.

[0047] A variety of suitable desiccant materials may be used. A "desiccant" material is understood to be a substance which induces or sustains a state of dryness in its vicinity, typically by absorbing water. The desiccant material, while itself being hygroscopic by promoting dehumidification, is a different material to the hygroscopic material used in accordance with the present invention possessing greater water absorption / adsorption abilities than the hygroscopic material and different deliquescent properties than the hygroscopic material. Typically, the desiccant material is suitable for human consumption. In some preferred embodiments, the desiccant material is a salt. In some embodiments, the desiccant material is selected from a calcium salt, a copper salt, a magnesium salt, a potassium salt and a sodium salt, and hydrates thereof. In some particular embodiments, the desiccant material is selected from calcium chloride, calcium oxide, calcium sulphate, copper sulphate, magnesium chloride, magnesium sulphate, potassium carbonate, potassium hydroxide, sodium, sodium chloride, sodium hydroxide, sodium sulphate and hydrates thereof. Such hydrates may be, for example, magnesium chloride hexahydrate or magnesium sulphate heptahydrate. Said desiccant salts find particular use in the compositions of the invention since they are also mineral sources and are permitted for use in infant formula in jurisdictions such as Australia, whilst also possessing anticaking / desiccant properties. In particular embodiments, the desiccant material is selected from potassium carbonate,magnesium sulphate and calcium chloride; such salts are advantageous as they possess a relatively high solubility and absorption capacity, and are permitted nutritional additives in infant formula. In some preferred embodiments, the desiccant material is selected from magnesium sulphate and calcium chloride. In some embodiments, the desiccant material may be a combination of two or more desiccant materials, such as a combination of two or more of the desiccant materials mentioned above.

[0048] In some embodiments, the desiccant material has a water absorption capacity of from about 5% (i.e. the desiccant material can absorb up to 5% of its weight in moisture) to about 300% at 50% relative humidity (RH). In some embodiments, the desiccant material has a water absorption capacity of from about 18% to about 150% at 50% RH. In some preferred embodiments, the desiccant material is deliquescent.

[0049] Desiccants with a high deliquescence relative humidity (DRH) are preferable since they do not begin to deliquesce at lower humidities. In some preferred embodiments, the desiccant has a DRH value of at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80% or at least about 85%. Exemplary desiccant salts include, for example, magnesium sulphate, potassium chloride, potassium fluoride, disodium hydrogen phosphate, calcium bromide, iron chloride, and sodium thiosulphate.

[0050] In some preferred embodiments, the desiccant is a salt hydrate that contains water of crystallization and may exist in various hydrated forms. Examples of such salts include magnesium sulphate and sodium carbonate. This is in contrast to salts such as potassium chloride, which absorbs water at an ionic level. In some embodiments it is preferable to use salts with greater solubility in water, such as more highly hydrated salts (for example magnesium sulphate heptahydrate as opposed to magnesium sulphate monohydrate), to increase the total solids spray dried for more efficient drying.

[0051] In particularly preferred embodiments, the desiccant material is magnesium sulphate, for example magnesium sulphate heptahydrate or magnesium sulphate monohydrate. Spray drying of magnesium sulphate heptahydrate generates magnesium sulphate monohydrate which, by virtue of its greater water retention properties, the presentinventors suggest is beneficial in maintaining the activity of choline chloride in a composition of the present invention.

[0052] Typically in accordance with the present invention, the ratio of the hygroscopic material to the desiccant material in the composition is up to about 100:1, for example from about 0.1:1 to about 100:1, for example from about 1:1 to about 100:1. In some embodiments, the ratio of the hygroscopic material to the desiccant material in the composition is from at least about 0.99:0.01 to at least about 0.5:0.5. In some embodiments, the ratio of the hygroscopic material to the desiccant material in the composition is from about 1:1 to about 30:1. In some embodiments, the ratio of the hygroscopic material to the desiccant material is from at least about 0.99:0.01 to at least about 0.6:0.4, at least about 0.99:0.01 to at least about 0.7:0.3, at least about 0.99:0.01 to at least about 0.8:0.2, at least about 0.99:0.01 to at least about 0.9:0.1, or at least about 0.99:0.01 to at least about 0.96:0.04. In some embodiments, the ratio of the hygroscopic material to the desiccant material is about 0.99:0.01, about 0.98:0.02, about 0.97:0.03, about 0.96:0.04, about 0.95:0.05, about 0.94:0.06, about 0.93:0.07, about 0.92:0.08, about 0.91:0.09, or about 0.9:0.1, optionally about 0.96:0.04. In some embodiments wherein the hygroscopic material and the desiccant material are present in the aforementioned ratios, the hygroscopic material is a choline salt, for example choline chloride, and the desiccant material is a salt such as magnesium sulphate, for example magnesium sulphate heptahydrate.

[0053] In some embodiments, the composition comprises at least about 30% of the hygroscopic material by weight, for example at least about 40% of the hygroscopic material by weight, for example at least about 45% of the hygroscopic material by weight, for example at least about 50% of the hygroscopic material by weight, for example at least about 55% of the hygroscopic material by weight, for example at least about 60% of the hygroscopic material by weight.

[0054] Compositions of the present disclosure may comprise one or more further components. Such components may be present, for example, to address other nutritional needs in a nutritional product into which the composition is intended to be incorporated, and / or to further tailor the properties of the composition. For example, compositions may comprise proteins, polysaccharides, carbohydrates, lipids such as polyunsaturated fattyacids, for example long chain polyunsaturated fatty acids, antioxidants, preservatives anti- caking agents, flavouring agents, colouring agents, vitamins, minerals, amino acids, chelating agents, emulsifiers and the like. Suitable antioxidants are well known to those skilled in the art, and may be water soluble or oil soluble. Suitable water soluble antioxidants include, for example, sodium ascorbate, calcium ascorbate, potassium ascorbate, ascorbic acid, glutathione, lipoic acid and uric acid. Suitable oil soluble antioxidants include, for example, tocopherols, ascorbyl palmitate, tocotrienols, phenols, polyphenols and the like. The compositions may further comprise one or more emulsifiers. The emulsifiers may be high molecular weight emulsifiers, low molecular weight emulsifiers, or a mixture thereof. In the context of this specification, the term "low molecular weight emulsifier" is understood to mean an emulsifying agent having a molecular weight of 1000 g / mol or less. In the context of this specification, the term "high molecular weight emulsifier" is understood to mean an emulsifying agent having a molecular weight of greater than 1000 g / mol. Non-limiting examples of emulsifiers include: low molecular weight emulsifiers with a high HLB (hydrophile-lipophile balance) value, such as Tween emulsifiers, some lecithins, mono- and diacylglycerols; high molecular weight emulsifiers with a high HLB value, such as polysaccharides with emulsifying groups; and low molecular weight emulsifiers with a low HLB value such as Span emulsifiers, polyglycerol polyricinoleate and some lecithins. Other suitable emulsifiers will be well known to those skilled in the art. An emulsifier may be present, for example, in an amount between about 0.1% and 3% of the total weight of the composition, or in an amount between about 0.1% and about 2%, or in an amount between about 0.1% and 0.5%, or in an amount between about 0.1% and 0.3%, of the total weight of the composition. For example, the emulsifier may be present in an amount of about 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 1.6%, 1.7%, 1.8%, 1.9% or 2% of the total weight of the composition.

[0055] In some embodiments, compositions of the present disclosure may comprise one or more processing aids, for example to assist with the drying process. In some exemplary embodiments, silicon dioxide is used as a processing aid; in some such embodiments, silicon dioxide is present in the composition. Silicon dioxide may be added during, for example, spray-drying, for purposes such as improving powder throughput. In some such embodiments, silicon dioxide may be present at an about of up to about 5% by weight, for example up to about 3% by weight, for example up to about 1.5% by weight, preferably upto about 1% by weight of the solid composition. In some embodiments, tricalcium phosphate (TCP) is used as a processing aid; in some such embodiments the TCP is present in the composition. In some embodiments, TCP is added during spray-drying, for example to improve powder throughput. In some embodiments, TCP is present in an amount of up to about 20% for example up to about 15%, preferably up to about 10% by weight of the solid composition.

[0056] The present disclosure further relates to a process for preparing a solid composition comprising a hygroscopic material, such as the solid compositions described herein, the process comprising: a) providing a liquid composition of a hygroscopic material and a desiccant material b) drying the solution of step a) to provide a solid composition.

[0057] The liquid composition of step a) is preferably a solution, preferably an aqueous solution, and may be provided by, for example, hydrating a mixture of a hygroscopic material and a desiccant material, or, for example, by preparing separate solutions of a hygroscopic materials and a desiccant material and combining them before step b). In some embodiments, the liquid composition is an emulsion or suspension.

[0058] Drying in step b) may be carried out by any suitable process to remove a liquid solvent or carrier, typically water, from the liquid composition of step a), to provide a solid composition. For example in some embodiments, the drying may be sufficient to produce a free-flowing powder with particle size in the ranges disclosed hereinabove. Drying may be carried out by, for example, spray drying, freeze drying, drum drying, fluid bed drying or ribbon drying, optionally spray drying in particular embodiments.

[0059] The solid composition may be a solid composition as described herein. In particularly preferred embodiments, the solid composition is a powdered or spray-dried composition, and step b) comprises spray-drying the liquid composition, for example the solution, of step a).

[0060] As discussed above, processing aids such as silicon dioxide and / or TCP may be added, for example during step b), for example to assist with drying such as spray-drying.

[0061] Spray-drying is a widely used technique for the preparation of powders. Spray- drying may be carried out on any suitable equipment and under conditions suitable to prepare the solid composition. Such conditions may vary depending on, for example, the nature of the hygroscopic material, the desiccant material, and their concentrations in the liquid composition, such as the solution, of step a). In some embodiments, spray-drying may be carried out at an inlet temperature of at least about 160°C, and an outlet temperature of at least about 90°C, for example an inlet temperature of about 180 °C to 220oC and an outlet temperature of about 95°C.

[0062] In some embodiments, for the liquid composition of step a), the solid ingredients comprise at least about 10%, at least about 20%, at least about 30%, at least about 40%, at least about 50%, at least about 60% or at least about 70%, at least about 80%, at least about 90%, at least about 95%, or at least about 99% of the liquid composition by weight. In other words, the liquid composition may comprise at least about 10%, at least about 20%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, at least about 95% or at least about 99% of the combined weight of the hygroscopic material and the desiccant material in the liquid composition. The hygroscopic material and desiccant salt are hydrated to the desired total solids. The percent total solids may depend on the specific desiccant material employed.

[0063] In a liquid composition, to calculate the total solids: % total solids of liquid composition = X 100As discussed above, in some embodiments the liquid composition total solid content may be at least about 20%, 30%, 40%, 50%, 60%, 70% or 80% by weight. In some embodiments, the total solid content of the liquid composition is from about 40% to about 70%, for example from about 50% to about 60%.

[0064] In some embodiments, the hygroscopic material is a choline salt and the liquid composition comprises at least or about 10%, at least or about 15%, at least or about 20%,at least or about 25%, at least or about 30%, at least or about 35%, at least or about 40%, at least or about 45%, at least or about 50%, at least or about 55%, at least or about 60%, at least or about 65%, at least or about 68%, or at least or about 70% choline based on the combined weight of the hygroscopic material and the desiccant material in the liquid composition.

[0065] Other components may be present in the liquid composition, such as the solution, of step a) as described herein, for inclusion in the eventual solid composition.

[0066] To calculate the amount of hygroscopic material in the solid composition: % hygroscopic material of solid composition = X 100wherein mhygroscopic material = mass of the hygroscopic material in the solid composition; and mdesiccant material = mass of desiccant material in the solid composition.

[0067] In some particular embodiments, the hygroscopic material is a source of choline, for example a choline salt, preferably choline chloride. In an exemplary embodiment, the solid composition comprises 96% choline chloride and 4% magnesium sulphate heptahydrate, resulting in 700mg / g (or 70%) choline. In another exemplary embodiment, the composition comprises 80.4% choline chloride and 19.4% magnesium sulphate heptahydrate, resulting in 600.0mg / g (or 60.00%) choline. In another exemplary embodiment, the composition comprises 66.7% choline chloride and 33.3% magnesium sulphate heptahydrate, resulting in 500.0mg / g (or 50.00%) choline.

[0068] In some embodiments, the solid composition is in the form of a powder, optionally a spray dried powder comprising up to about 70% choline, for example up to about 69% choline, preferably up to about 68% choline. Such choline contents were found to provide solid compositions with advantageous powder properties, as described in the Examples below. In some embodiments, the solid composition comprises at least about 5% choline, at least about 10% choline, at least about 20% choline, at least about 30% choline,at least about 30% choline, at least about 40% choline, at least about 45% choline, or, in some preferred embodiments at least about 50% choline.

[0069] In some particular embodiments, the solid composition comprises from about 5% choline to about 68% choline, for example from about 10% to about 68% choline, for example from about 20% choline to about 68% choline, for example from about 30% choline to about 68% choline, for example from about 40% choline to about 68% choline chloride for example from about 45% choline to about 68% choline, or for example from about 40% choline to about 60% choline, for example from about 45% choline to about 60% choline, preferably about 45% choline to about 55% choline. In some exemplary embodiments, the composition comprises about 50% choline.

[0070] The present disclosure further relates to a solid composition obtained by a process described herein, for example a spray-dried composition obtained by a process described herein.

[0071] As discussed herein and demonstrated by the Examples below, the present inventors have surprisingly found that compositions of choline chloride may be prepared with reduced agglomeration (i.e., reduced lumping or caking) when spray dried with a desiccant material, such as any desiccant material described herein. Accordingly, the present disclosure further relates to a method of improving powder flowability of a hygroscopic material, comprising: a) providing a liquid composition of said hygroscopic material and a desiccant material b) drying the liquid composition of step a) to provide a solid composition, thereby improving powder flowability of the hygroscopic material.

[0072] In preferred embodiments, the liquid composition is a solution, preferably an aqueous solution, as described above.

[0073] In preferred embodiments, step b) comprises spray-drying the solution of step a) to provide a spray-dried composition. The process and solid and liquid compositions may be as described elsewhere herein.

[0074] The present disclosure further relates to liquid compositions comprising a hygroscopic material and a desiccant material as described herein, for example a solution, emulsion or suspension. The liquid composition may be as described herein in relation to solid compositions and processes mutatis mutandis. Such liquid compositions may find use in processes described herein, for drying for preparation of a solid composition as described herein.

[0075] Without wishing to be bound by theory, it is believed that the hygroscopic material and the desiccant material described herein, optionally in combination with the processes described herein, afford solid compositions which are powders rather than clumps of solid material. The powders, in turn, facilitate easier use of the solid compositions in the applications described herein.

[0076] Compositions contemplated herein may be formulated for administration to subjects by any suitable route, typically oral administration. The composition may be in liquid or solid form, and may be consumed as such (for example in the form of capsules or other suitable solid form, or in the form of a powder to be reconstituted with a liquid before consumption, thereby providing a liquid composition for administration to subjects). Alternatively, the compositions may be incorporated into a nutritional formulation, such as a food or beverage product or nutritional supplement as will be well known those skilled in the art. Suitable nutritional formulations will be well known those skilled in the art and include, for example, dietary supplements, infant formula and nutritional formula formulated for other age groups or specific subject groups including for example pregnant individuals and lactating individuals. In the context of this specification, the term "infant formula" includes compositions that are intended as breast milk replacements or supplements and also milk fortifiers. Nutritional formula can be designed and formulated for humans or other animals, including companion animals (e.g. dogs and cats), livestock (e.g. cattle, sheep, pigs, goats, horses, donkeys etc) and performance animals such as racehorses. Foods containing compositions of the present invention may include snacks or fortified food products for human consumption, or treats or food for animals such as pet food and livestock feed.

[0077] Accordingly, the present disclosure relates to nutritional formulations, includingfood or beverage products or nutritional supplements, for example infant formulas, breastfeeding and lactation formula and pregnancy formula, comprising a composition of the present disclosure.

[0078] The nutritional formulation may further comprise one or more antioxidants or preservatives. Suitable antioxidants are well known to those skilled in the art and may include, but are not limited to green tea extract, tocopherols, tocotrienols and ascorbic acid, including salts and derivatives thereof. The nutritional formulation may comprise a water- soluble antioxidant and / or a lipid-soluble antioxidant. In one embodiment, the nutritional formulation may comprise an ascorbate salt, such as sodium ascorbate, and a lipid-soluble ascorbate derivative, optionally a fatty acid ester of ascorbic acid, optionally ascorbyl palmitate.

[0079] The compositions of the invention may further comprise additional components, for example, flavouring agents, colouring agents, vitamins, minerals, amino acids, chelating agents, flow agents and the like.

[0080] It will be appreciated by persons skilled in the art that numerous variations and / or modifications may be made to the invention without departing from the spirit or scope of the invention as broadly described. The present embodiments are, therefore, to be considered in all respects as illustrative and not restrictive.

[0081] The present invention will now be further described in greater detail by reference to the following specific examples, which should not be construed as in any way limiting the scope of the invention. Examples Example 1 – Spray drying choline chloride with desiccant salts

[0082] Choline chloride was spray-dried (Buchi B-290 spray dryer) together with various desiccant salts at a ratio of 1:1. Guar gum was also tested with magnesium sulphate, to assess for a potential synergistic effect. The particular desiccant salts below were chosen due to their allowability in relatively high levels as a source of minerals in infant formula,their relatively high solubility and their relatively high absorption capacity. Magnesium sulphate heptahydrate was selected as a stable and affordable form of magnesium sulphate.

[0083] The following combinations were spray dried at 80% total solids: 1. Choline chloride (positive control) 2. Choline chloride: Magnesium Sulphate Heptahydrate (1:1) 3. Choline chloride: Magnesium Sulphate Heptahydrate: Guar Gum (1: 1: 0.02) 4. Choline chloride: Calcium chloride (1:1)

[0084] The spray dried products were stored in aluminium bags and kept open. Products were visually assessed for free flowability.

[0085] After 7 days, products containing magnesium sulphate heptahydrate were observed to be more stable / free flowing than the other products. Example 2 – Ratio of choline chloride to desiccant salt

[0086] Based on the results of Example 1, magnesium sulphate heptahydrate was selected to further investigate different desiccant addition rates. These experiments aimed to find the highest amount of choline that may be spray dried with magnesium sulphate heptahydrate such that the product remains stable for up to a day. Formulations of 60-80% total solids were prepared as follows: 1. Choline chloride: Magnesium Sulphate Heptahydrate (0.2: 0.8) 2. Choline chloride: Magnesium Sulphate Heptahydrate (0.4: 0.6) 3. Choline chloride: Magnesium Sulphate Heptahydrate (0.6: 0.4) 4. Choline chloride: Magnesium Sulphate Heptahydrate (0.8: 0.2)

[0087] Choline chloride: Magnesium Sulphate Heptahydrate (0.6: 0.4), was found to be stable for up to 2 weeks once the bag was opened and then just closed with a paper clip, without nitrogen flush or sealing.Example 3 – Conditions for pilot scale formulation

[0088] Two salt solutions of differing choline level (50% and 60%) were formulated to be spray dried into a powder on a larger pilot scale. Table 1 below illustrates the choline chloride to magnesium sulphate heptahydrate ratios and total solids. Table 1 f ay

[0089] Previously, salts were hydrated as a dry blend. For consistency, magnesium sulphate heptahydrate was first hydrated followed by choline chloride for ongoing trials. More water was required to fully dissolve the magnesium sulphate heptahydrate salt (solubility 1.13 g / ml) before the addition of choline chloride to provide 50% choline ('the 50% system') in the final spray dried powder.

[0090] The 50% system was first spray dried using an SPX Anhydro Centrifugal Atomiser (SPX Flow Technology MS-150 spray dryer) at ~35000 rpm. Small droplets of water were observed on the dryer chamber window which meant ineffective evaporation of water due to possibly, larger atomized droplets. To circumvent this issue, the SPX co-current nozzle atomizer was used at a pneumatic pressure of 4 bar.. Different process conditions were set to primarily examine if a slower feed flow rate to the dryer would produce powders of low moisture content. Higher inlet and outlet temperatures (170 °C and 95 °C, respectively) were used for the 60% system. It was observed that higher inlet and outlet temperatures are required to ensure low moisture contents of this hygroscopic material. Conditions and resulting moisture contents are shown in Table 2 below.Table 2. Choline content in powder and powder moisture content. tExample 4 – Conditions for bench scale formulation

[0091] Each of 45%, 60% and 70% choline chloride and magnesium sulphate heptahydrate solutions in final powder form was reworked to determine the minimum amount of water required to completely dissolve the salts, as shown in Table 3 below. These salt solutions were then spray dried at inlet and outlet temperatures shown in the table. Table 3 Choline content in powder under varying drying conditions C; C; 99 °C mp he

[0092] Table 4 below provides water activity (aW) for solutions spray dried at 60% total solids. Generally spray-dried powder formulations with higher choline chloride content have higher water activity values. Table 4 Water activity at various choline contentsExample 5 – Dry blending choline chloride + salt

[0093] Magnesium sulphate heptahydrate was oven-dried to produce magnesium sulphate monohydrate. This was then dry mixed with grounded choline chloride. Moisture absorption of a choline chloride control sample (73% choline) and a dry mixed sample (60% choline) with magnesium sulphate monohydrate was compared. There were no significant differences between samples examined over 24h at relative humidity of 65-70%. It was visibly apparent that the magnesium sulphate monohydrate was largely intact and did not reach deliquescence. This is unlike the spray-dried solution comprising both the hygroscopic (choline chloride) and desiccant (magnesium sulphate heptahydrate) material. The latter sample at 60% choline was largely of fine powder even after >12h exposure to 60-70% relative humidity. Example 6 – XRD results

[0094] X-ray diffraction analysis was used to examine the composition of spray-dried choline chloride and magnesium sulphate heptahydrate powder to determine whether anynew compounds were formed through the process. However, as the sample was adsorbing moisture under a non-climate-controlled chamber, changes in the crystallographic structure were also observed. The scans identified mainly choline chloride and magnesium sulphate monohydrate (kieserite). The peaks for magnesium sulphate monohydrate were broad and reduced in intensity faster than choline chloride which indicated that kieserite was adsorbing moisture more efficiently than choline chloride. This phenomenon corresponds to the function of a desiccant where moisture uptake is directed away from the hygroscopic material and adsorbed by the desiccant material. Example 7 – Moisture sorption isotherm results

[0095] A moisture sorption isotherm represents the relationship between moisture content and water activity at constant pressure and temperature for a specific material. Moisture content is the proportion of total water, available and bound, in a product / material. The water activity is a measurement of the water that is available for biological reactions or media for micro-organisms to grow.

[0096] Three choline chloride samples were compared: (i) a control composition with 73.1% choline chloride and no desiccant salt; (ii) a test composition containing 50% choline chloride with magnesium sulphate as desiccant (0.67 ChCl :0.33 MgSO4.7H2O); and (iii) a test composition containing 60% choline chloride with magnesium sulphate as desiccant (0.80 ChCl :0.20 MgSO4.7H2O). The isotherms were done at 25°C by using a Vapour Sorption Analyser (VSA). As shown in Figure 2, at a given moisture content, the water activity is higher for the control composition than the test compositions (containing the desiccant), until a moisture content of about 31% is reached. The higher proportion of magnesium sulphate in the 50% choline powder in contrast to 60% choline powder showed reduced water activity at a given moisture content. Without wishing to be bound by theory, the inventors suggest that the test composition is able to bind more water molecules to the product, due to the desiccant property of the salt, which reduces its water activity by decreasing the number of free water molecules in the system. Example 8 – Further study on spray-dried solutions at a range of choline contents

[0097] Solutions of choline chloride and magnesium sulphate at various ratios and choline contents were spray dried at 170 °C inlet and outlet of 95-98 °C on bench-scale (Buchi B-290). Details of the resulting powder compositions are provided in Table 5 below. Table 5 Observations across powder samples with varying choline content od y) y) et

[0098] Generally, choline solution (10 to 68% active on dry solids basis) was spray dryable with no observed wet patches / beads on the dryer. 70% choline powder was moist and comparatively stickier upon collection.

[0099] Powder samples were subjected to storage at 40 °C / 75% relative humidity (RH) over a 3-hour duration, except for the 70% sample which was subjected to conditions of 22 °C and 50% RH overnight. Powder samples subjected to 40 °C / 75%RH over a 3-hour duration remained largely intact. 10% and 35% choline samples were visibly dry. 65% and 68% samples observed moistness on the surface. The 70% choline powder liquefied. Example 9 – Preparation of spray-dried powders with alternative desiccant salts

[0100] Spray-dried choline powders were prepared using different desiccant salts, as summarised in Table 6 below. The total solids were adjusted to 38%TS for potassium chloride samples as the inherent solubility is lower (solubility: 34g per 100g water i.e. ~25%) than magnesium sulphate heptahydrate (solubility: 150g per 100g water i.e. ~60%).Table 6 Observations of 50% choline powder spray dried with different desiccant salts ly of

[0101] Desiccant salts with a high deliquescence relative humidity (DRH) are preferable as they do not begin to deliquesce at lower humidities. As calcium chloride deliquesces at 32%RH, spray drying was challenging with wet patches and pools observed on the dryer and in the powder collection pot as such, no powder could be collected.

[0102] 50% choline powder samples with either magnesium sulphate or potassium chloride were subjected to 40 °C / 75%RH over a 3-hour period. The moisture absorption uptake was similar at a rate of 0.14g per hour of a 10 g sample contained in a beaker. At the end of the 3-hour period, both samples were largely intact with moistness detected on the surface.

[0103] Apart from DRH as a factor, the way in which water is incorporated is different across salts. Potassium chloride absorbs water at an ionic level whilst other salts such as magnesium sulphate can exists in varying hydrated forms where n number of water molecules are enclosed within its crystal lattice. Hence, sodium carbonate was examined as it exists in a solid form, for example as a decahydrate (10H2O), and has a high DRH. However, as the solubility is low, the solution was spray dried at 35%TS to produce a 68% choline powder and at 25%TS to produce a 50% choline powder. The spray dried powder with sodium carbonate was visibly similar to choline powder with magnesium sulphate; lightweight and powdery. However, the powder was comparatively stickier after storage at 40 °C, 75%RH. The prepared compositions are shown in Table 7 below. Improvements were made to processing conditions on the dryer to assist with a low total solids feed. A dry 50% choline powder with sodium carbonate was produced with considerably less clumps and remained largely intact after high temperature and humidity storage (40 C / 75%RH) over a 3-hour period. Table 7 Choline powder matrix with sodium carbonate ut H nd e. tly H

Claims

Claims<sup>1.A solid composition comprising a hygroscopic material and a desiccant material, wherein the hygroscopic material is choline chloride.

2. The solid composition according to claim 1, which is a powder.

3. The solid composition according to claim 1 or 2, which is a dried composition.

4. The solid composition according to any one of claims 1 to 3, wherein the composition is a spray-dried composition.

5. The solid composition according to any one of claims 1 to 4, wherein the desiccant material is a salt.

6. The solid composition according to claim 5, wherein the desiccant material is selected from a calcium salt, a copper salt, a magnesium salt, a potassium salt and a sodium salt, and hydrates thereof.

7. The solid composition according to claim 6, wherein the desiccant material is selected from calcium oxide, calcium sulphate, copper sulphate, magnesium chloride, magnesium sulphate, potassium carbonate, potassium hydroxide, potassium chloride, potassium fluoride, sodium chloride, sodium hydroxide, sodium sulphate, disodium hydrogen phosphate, calcium bromide, iron chloride, sodium thiosulphate, and hydrates thereof.

8. The solid composition according to claim 7, wherein the desiccant material is selected from sodium carbonate, potassium chloride and magnesium sulphate.

9. The solid composition according to claim 8, wherein the desiccant material is magnesium sulphate heptahydrate or magnesium sulphate monohydrate.

10. The solid composition according to any one of claims 1 to 9, wherein the ratio of the hygroscopic material to the desiccant material in the composition is from about 1:1 to about 30:

1.

11. The solid composition according to claim 10, wherein the ratio of the hygroscopic material to the desiccant material in the composition is about 0.96:0.

04.

12. The solid composition according to any one of the preceding claims, wherein the composition comprises at least about 40% choline.

13. The solid composition according to any one of the preceding claims, wherein the composition comprises up to about 69% choline.

14. The solid composition according to any one of the preceding claims, wherein the composition comprises from about 40 to about 60 % choline.

15. The solid composition according to claim 14, wherein the composition comprises about 50% choline.

16. The solid composition according to any one of the preceding claims, further comprising a processing aid.

17. The solid composition according to claim 16, wherein the processing aid comprises silicon dioxide and / or tricalcium phosphate.

18. The solid composition according to claim 17, wherein silicon dioxide is present in the composition in an amount of up to about 1% by weight.

19. The solid composition according to claim 17 or 18, wherein tricalcium phosphate is present in the composition in an amount of up to about 10% by weight.

20. A process for preparing a solid composition comprising a hygroscopic material, comprising:a) providing a liquid composition of a hygroscopic material and a desiccant material, wherein the hygroscopic material is choline chloride; and b) drying the liquid composition of step a) to provide a solid composition.

21. The process according to claim 20, wherein the solid composition is a spray-dried composition and step b) comprises spray-drying the liquid composition of step a).

22. The process according to claim 20 or 21, further comprising adding a processing aid during step b).

23. The process according to claim 22, wherein the processing aid comprises silicon dioxide and / or tricalcium phosphate.

24. The process according to any one of claims 20 to 23, wherein the solid composition is a composition according to any one of claims 1 to 19.

25. The process according to any one of claims 20 to 24, wherein the liquid composition is a solution of a hygroscopic material and a desiccant material.

26. The process according to any one of claims 20 to 25, wherein the liquid composition of step a) comprises at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, at least about 95%, or at least about 99% of the hygroscopic material based on the combined weight of the hygroscopic material and the desiccant material in the composition.

27. The process according to any one of claims 20 to 26, wherein the hygroscopic material is a choline salt and the liquid composition of step a) comprises at least about 40%, at least about 45%, at least about 50%, at least about 60% or at least about 70% choline based on the combined weight of the hygroscopic material and the desiccant material in the composition.

28. A solid composition obtained by a process according to any one of claims 20 to 27.

29. A method of improving powder flowability of a hygroscopic material, comprising a) providing a liquid composition of said hygroscopic material and a desiccant material b) drying the liquid composition of step a) to provide a solid composition, thereby improving powder flowability of the hygroscopic material, wherein the hygroscopic material is choline chloride.

30. The method of claim 29, comprising the process of any one of claims 20 to 27.

31. A liquid composition comprising a hygroscopic material and a desiccant material, wherein the hygroscopic material is choline chloride.

32. The liquid composition according to claim 31, wherein the liquid composition is a solution of a hygroscopic material and a desiccant material.

33. The liquid composition according to claim 31 or 32, wherein the composition comprises at least about 40%, at least about 45%, at least about 50%, at least about 60% or at least about 70% choline based on the combined weight of the hygroscopic material and the desiccant material in the liquid composition.

34. The liquid composition according to any one of claims 31 to 33, wherein the desiccant material is selected from a calcium salt, a copper salt, a magnesium salt, a potassium salt and a sodium salt, and hydrates thereof.

35. The liquid composition according to claim 34, wherein the desiccant material is magnesium sulphate, optionally magnesium sulphate heptahydrate or magnesium sulphate monohydrate.

36. A nutritional formulation comprising the solid composition according to any one of claims 1 to 19 or claim 28.

37. The nutritional formulation according to claim 36, which is an infant or other nutritional formula, or a dietary supplement.

38. Use of the solid composition according to any one of claims 1 to 19 or claim 28 for preparing a nutritional formulation, food, beverage, or dietary supplement.

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