Introduction

The present invention relates to formulations of stimulants and vitamins, in particular to formulations combining B vitamins and methyl-xanthine stimulants such as caffeine, and relates especially to drinking straws containing such formulations and to methods of making the same.

Background to the Invention

Many preparations are available for purchase across the counter that provide, or purport to provide, rapid increases in energy for the consumer. These may contain one or a cocktail of different stimulants and vitamins.

Drinks containing caffeine and / or taurine are well known. WO 2014/195907, for example, describes a coffee beverage comprising coffee solids or coffee flavour, sweeteners, acidifiers, flavourings and optionally one or more bioactive components such as caffeine, taurine, antioxidants, minerals and vitamins that are soluble in water. Similarly, WO 2012/120536 describes a high energy soft drink comprising sweetener, B vitamins, taurine and caffeine, together with other components such as flavours and colouring agents.

In combined preparations of B and C vitamins it is known to provide these in solution form incorporating stabilizers, see e.g. US 2823167. It is known to provide drinking straws filled with pellets which dissolve in a beverage sucked through the straw by a user. The pellets typically contain various flavourings and sweeteners, but may also contain vitamins, minerals and other active ingredients. The pellets contained within such straws are made by a panning method, resulting in nonpareil pellets. These dissolve progressively, adding flavour to the beverage of 300-400ml, and not clogging typical filtration means. The panning method involves the addition of alternating quantities of a syrup and a powder to a rotating pan, building up layers on a core. As such nonpareil pellets are layered, and it is possible to view the layers under microscopic examination. For example see US 2009/0041904, which relates to filtration means for such straws. Straws with varying flavours have been manufactured by Unistraw Holdings Pte. Ltd. ("Unistraw") including Banana flavoured and Cookies and Cream flavoured. Unistraw have also manufactured a coffee flavoured straw. It has also been proposed to deliver probiotics via filled drinking straws. In order to maintain viability, probiotic material must be stored in dry conditions. US 2012/247993 describes the preparation of pellets for a filled straw in which the pellets contain probiotic material. The pellets are made by the standard wet panning process, and as this process involves water, the pellets must be dried after formation. This may, for example, be via freeze drying, fluid bed drying, pan or tray drying or other drying methods.

US3008/197141 describes a filled straw in which the contents is described as dried food. This term is said to cover powders, granules, beads. Freeze-dried soups are also suggested provided that they are of a specific grain size.

D vitamins are known to be unstable in the presence of water. Formulations containing D vitamins are therefore prepared with increased initial amounts to compensate for deterioration in storage.

It is desired to provide alternative formulations of energy-giving or energy-enhancing preparations and alternative delivery of such formulations.

An object of the invention is to provide alternative delivery of formulations of B vitamins alone or in combination with simulants. Embodiments have as object the provision of improved formulations and methods of making formulations and devices containing the formulations.

Summary of the invention

A drinking straw is provided comprising a plurality of pellets for oral delivery of an active agent, wherein the pellets comprise, as the active agent, a B vitamin disposed within a matrix formulation prepared by a substantially water-free granulation of pellet components. Formulations can contain a CNS stimulant such as caffeine. Granulation-based methods of making straws are provided that are water-free and preferably sugar free. Details of the Invention

Accordingly, the present invention provides a drinking straw comprising a plurality of pellets for oral delivery of an active agent, wherein the pellets comprise, as the active agent, (i) a CNS stimulant and (ii) a B vitamin disposed within a matrix formulation prepared by a substantially water-free granulation of pellet components.

Thus alternative and preferably improved delivery of the CNS stimulant and vitamin formulation can be achieved in the straw of the invention - by a user sucking drink, typically water, through the straw, dissolving or disintegrating the pellets to release the active agent(s).

In operation, straws of the invention, specifically the straws set out in examples below, have been found to be stable in storage, maintaining high levels of active agent(s) without decomposition thereof and releasing the active agents in a steady and reliable manner, in effect (when consumed) delivering a ready-to-drink beverage with long shelf-life and high levels of active agents.

Embodiments of the invention contain one or a plurality of B vitamins. Formulations can contain one or more of vitamins B1 , B2, B3, B6 and B12, and may optionally also contain inositol. Preferred formulations contain at least vitamin B12.

Particular formulations of the invention include all of vitamins B1 , B2, B3, B6 and B12 and also inositol (e.g. as myo-inositol). Commercial premixes are available containing all these combined. In a specific embodiment of the invention the formulation contains, as % by weight of the vitamin component:

vitamin B1 = 5 - 7 %

vitamin B2 = 5 - 7 %

vitamin B3 = 5 - 7%

vitamin B6 = 2 - 4 %

vitamin B12 = 70 - 80%

Inositol = 3 - 6 %

It is optional to provide one or a combination of CNS stimulants in the formulations of the invention. CNS stimulants are compounds that speed up the physical and mental process. Many CNS stimulants are chemically similar to the neurohormone norepinephrine. Other CNS stimulants include xanthines or closely related compounds. Other still do not fall into any specific chemical categories.

In preferred specific examples below, being examples of CNS stimulant-containing embodiments, the formulations comprise caffeine. More generally, the formulations can comprise one or more methyl xanthines, e.g. caffeine, theobromine and / or theophylline, or taurine. Typically, the CNS stimulant represents approximately 1 - 20% by weight of the formulation, preferably 1 - 10% by weight. The CNS stimulant typically comprises caffeine or taurine, preferably caffeine.

A CNS stimulant is optional, hence an embodiment of the invention provides a drinking straw comprising a plurality of pellets for oral delivery of an active agent, wherein the pellets comprise, as the active agent, a B vitamin disposed within a matrix formulation prepared by a substantially water-free granulation of pellet components.

It has been found by the inventors that vitamin stability in storage, especially for B vitamins, is an issue with formulations of this type. Further, it is believed that identification of this particular problem, namely that certain vitamins may decompose unacceptably in storage when in just-add-water formulations made by granulation methods of conventional choice, has not been highlighted previously. Stability of B vitamins in ready to drink beverage is, however, a known issue.

In methods of making pellets for use in the straws of the invention, water content is suitably kept to a minimum, i.e. standard water-based granulation methods are avoided in order to yield pellets that contain B vitamins and have acceptable stability. Known vitamin D formulations have stability issues, dealt with by preparing those formulations using conventional wet processes but increasing the amount of vitamin so that even after deterioration in storage an acceptable amount remains. A finding of the inventors is that this approach is not appropriate for B vitamins in filled straws because the products of degradation after exposure to moisture during manufacture are so unpleasant that the resulting formulations rapidly become unusable and/or refused by consumers. An advantage of the invention is the avoidance of water which dramatically reduces degradation of the B vitamins, and reduces or avoids patient compliance issues that would arise if the B vitamin break-down products were to rise above a minimally acceptable limit. A drinking straw of preferred embodiments is made by a granulation of pellet components wherein the water content of the granulation mix is 5% or less by weight. The process is essentially a dry one. Water content may further preferably, in the granulation mix, be 3% or less by weight.

The drinking straw of the invention is further preferably prepared by a granulation of pellet components and then forming pellets, and subsequently drying the formed pellets. This reduces water content in the final product and during storage. Drying preferably takes place as soon as possible after pellet formation.

Drying the formed pellets may comprise drying the pellets to a water content of 3% or less by weight, more suitably 2% or less by weight. In examples, the final water content was 1 % or less by weight.

Further preferred is for granulation to avoid using sugar. The resultant pellets, therefore comprise active agent disposed within a matrix formulation that is substantially sugar-free. To prepare such pellets, the sugar content of the granulation mix may be kept at 5% or less, more suitably 3% or less by weight, preferably 2% or less by weight.

Pellet size is suitably for the drinker to drink liquid through the pellets and receive a desired dose of vitamin and optionally CNS stimulant in a sensible volume of water, e.g. 350mL or less, 300ml_ or less or about 200 - 250mL. Generally, the drinking straw comprises pellets of diameter 1 mm to 5mm, more typically 2mm to 3mm. The straw may be of diameter 6mm - 13mm, more typically 7 - 9mm.

Pellets are retained within the drinking straw as is known in this art. Filtration means can be disposed, usually at or adjacent straw ends, to retain the pellets within the straw body. Typically, the body is an elongate tube containing a plurality of pellets comprising the active ingredient, the filters are disposed at or adjacent the ends of the tubular body to retain the pellets within the body, and the body and the filters are sized and arranged to allow a carrier liquid to be drawn therethrough such that passage of the liquid through the tube causes the pellets to dissolve or disintegrate thereby releasing active ingredient into the liquid. Examples of filters are known from EP 1509096 and WO 2007/098564. A method of preparing a drinking straw according to the invention, for oral delivery of an active agent, is similarly provided, the straw comprising (i) a CNS stimulant, and (ii) a B vitamin. The method comprises

a) combining the active agent with matrix components in the substantial absence of water to form a granulation mixture;

b) forming pellets from the granulation mixture; and

c) filling the straw with the pellets. Optional and preferred features of the method are as for the drinking straw per se as described above.

Again, as the CNS stimulant is optional, a method of making a drinking straw for oral delivery of an active agent comprising a B vitamin, may comprise

a) combining the active agent with matrix components in the substantial absence of water to form a granulation mixture;

b) forming pellets from the granulation mixture;

c) filling the straw with the pellets. The water content of the granulation mixture is suitably 5% or less by weight and may be 3% or less by weight. In effect the process is essentially a dry granulation, yielding straws with higher stability, exhibiting reduced decomposition of active agent during production and in storage. Straw manufacture preferably comprises drying the formed pellets, to further reduce the end water content. The formed pellets may be dried to a water content of 3% or less by weight, preferably 2% or less by weight or, as per examples, to 1 % or less by weight. Preferred methods also comprise combining the active agent with matrix components in the substantial absence of water and in the substantial absence of sugar to form the granulation mixture. The sugar content of the granulation mixture may be 5% or less, 3% or less, or 2% or less by weight. In this context, sugar refers to sucrose, glucose, galactose, lactose and fructose; hence sugar-free and similar terms indicate absence of all these. In a method of making pellets described in more detail below, pellets are formed by a combination of extrusion and breaking the extruded material into crude pellets which are then made more regular. A suitable method comprises extruding the granulation mixture to form an extrudate, breaking the extrudate and spheronizing the broken extrudate to form pellets. Pellets of diameter 2mm to 3mm are suitably formed.

In relation to both the pellets per se and the methods for making them, the formulations also generally comprise one or more sweeteners, flavourings, taste enhancers and/or diluents, with some such components falling into more than one category.

Suitable sweeteners include a number of different and known sugar substitutes, including e.g., aspartame, cyclamate, neotame, saccharin, steviol glycosides, sucralose and thaumatin. Flavourings, sweeteners and taste enhancers may be used in combination.

Examples of sweeteners, flavourings, taste enhancers and/or diluents are set out below. These components can make up from 5 to 40% by weight of the formulation, preferably from 10 to 30%, more preferably from 14 to 22%.

As set out in more detail in examples below, it is further usual for the formulations to include an acidulant, such as citric acid (available in different forms), lactic acid, malic acid, fumaric acid, tartaric acid or combinations of one or more of these, the acidulant being present in, say, 15 to 40% by weight, preferably from 20 to 35%, more preferably from 24 to 29% by weight.

To aid processing of the pellets and formation of regular pellets, a spheronization aid may be employed, generally at a level of up to 10%. Suitable spheronization aids include sugar alcohols, such as sorbitol, xylitol, maltitol and mannitol, and celluloses and cellulose derivatives, such as methylcellulose or hydroxypropyl cellulose.

The pellets are retained in the straw and released upon combination with liquid, e.g. water or possibly flavoured water or other drink. Binders are used to maintain pellet integrity and allow controlled dissolution. One or more binders (including controlled- release agents and/or film formers) are included in the granulation mix, at fairly high levels by weight, typically from about 30% up to about 60% by weight, preferable in the range 35% to 50%. Suitable binders include polysaccharides and hydrolyzed starch derivatives accepted for food additive use, e.g. maltodextrins, guar gum, gum Arabic, carrageenan gum and xanthan gum, polymers such as polyvinyl pyrrolidone and polyethylene glycol, cellulose, modified cellulose, e.g. microcrystalline cellulose, hydroxypropyl cellulose and hydroxypropyl methylcellulose. Specific examples are noted below.

A small amount of colour may be added, often post pellet formation, to a typical final level of up to 1 % by weight.

The invention extends also to straws obtainable by performing the methods of the invention. Specific straws also form further embodiments of the invention. Thus, the invention also provides:

(a) a drinking straw comprising a plurality of pellets for oral delivery of an active agent, wherein the pellets comprise, as the active agent, (i) a CNS stimulant and (ii) a B vitamin disposed within a matrix formulation having a water content of 1 % or less by weight;

(b) a drinking straw comprising a plurality of pellets for oral delivery of an active agent, wherein the pellets comprise, as the active agent, a B vitamin disposed within a matrix formulation having a water content of 1 % or less by weight;

(c) a drinking straw comprising a plurality of pellets for oral delivery of an active agent, wherein the pellets comprise, as the active agent, (i) a CNS stimulant and (ii) a B vitamin disposed within a matrix formulation having a water content of 1 % or less by weight and a sugar content of 3% or less by weight; and

(d) a drinking straw comprising a plurality of pellets for oral delivery of an active agent, wherein the pellets comprise, as the active agent, a B vitamin disposed within a matrix formulation having a water content of 1 % or less by weight and a sugar content of 3% or less by weight.

Optional and preferred features of other aspects of the invention provide further optional and preferred features of these embodiments (a) - (d).

Specific embodiments of the invention are set out in examples below. In particular, formulations of the invention may have ingredients in the ranges in the following table: Ingredient Specific examples of ingredient Amount, Amount by weight

Vitamins • B1

• B2

• B3 50mg

• B6 3.3%

• B12

• M-inositol

CNS Stimulants • Caffeine 88mg

5.9%

Sweeteners, • Steviol glycosides

Flavourings, Taste • Flavouring (e.g. mango,

enhancers, Diluents apple, blackcurrant, cherry, 230 - 315mg,

orange, lemon, lime and/or 15.3 - 21.0% mint)

Acidulants • Citric acid

• Tartaric acid

370mg - 425mg,

• Malic acid

24.7 - 28.3%

• Fumaric acid

• Lactic acd

Spheronization aids • Mannitol, Maltitol 95mg

• Hydroxypropyl cellulose 6.3%

Binders (including film • Maltodextrin

formers, controlled- • Xanthan gum

515mg - 657mg, release agents) • Carrageenan gum

34.3 - 43.8%

• Hydroxypropyl

methylcellulose

Colourings • Colour 2mg - 12mg,

0.1 - 0.7%

Examples The invention is now illustrated in specific examples below. Example 1

Drinking Straw Containing Cherry Flavour Granules

Cherry flavoured energy granules for filling straws were prepared as follows:

A dry formulation according to Table 1 (water content approximately 4% by weight) but excluding any colourings, was thoroughly mixed and sifted.

Table 1 - Ingredients list for cherry flavoured granules

The sifted mixture was granulated using a roller compaction machine, capable of compressing and extruding the mixture, using an auger-feeding mechanism, into strings for granule milling. The quality of the extruded strings was maintained due to the presence of the binder.

Granule milling to desired sizes was achieved by spheronization. Successful spheronization requires the extruded mixture to maintain plasticity; this was achieved through the presence of the spheronization aids, e.g. L-hydroxypropylcellulose and in this case mannitol. The strings enter the spheronizer and fragment as they make contact with a rotating disc. Pellet-like granules, approximately 3mm, and usually within the range of 2-5mm in diameter, were thus produced. The granules were then dried before being sprayed with the red colouring mentioned in Table 1 . The sprayed granules were then further dried, before being passed over a series of meshes to capture granules ranging in diameter from 2-5mm. Measuring water loss on drying indicated a final water content in the pellets of slightly less than 1 % by weight. Any granules outside of this size range were recycled via re-entry into the roller compaction machine.

Drinking straws of diameter 8mm were filled with the anhydrous granules in the desired quantity (a fill of approximately 30%), then conventional straw filtration means applied to both ends of the straw, before being wrapped and packaged for distribution.

The number of pellets and their size and dissolution rate was suitable for delivery of the active agents by sucking 200 - 250ml_ of room temperature water through the straw, this amount of water leaving a small residue only of undissolved pellets and fragments.

Example 2

Drinking Straw Containing Orange Flavour Granules

Orange flavoured energy granules for filling the straws were prepared as for cherry flavoured granules in Example 1 . However, as shown in Table 2, the ingredients of the mixture contained orange flavouring instead of cherry flavouring, and the colourings differed in order to produce an orange spray for the final granules.

Table 2 - Ingredients list for orange flavoured granules

Ingredients mg/straw % w/w Function

Vitamin Premix SRS 03

Contains: Vitamin

50 3.3

Vitamins B1 , B2, B3, B6, supplement

B12 and M-lnositol

Caffeine 88 5.9 CNS stimulant

Steviol glycosides 155 10.3 Sweetener

Orange flavour 160 10.7 Flavouring

Citric Acid 425 28.3 Acidulant

Spheronization

Mannitol 95 6.3

aid

Maltodextrin 515 34.3 Binder

Colour - yellow 2 0.1 Colouring

Colour - red 10 0.7 Colouring

Total 1500 100

Example 3

Drinking Straw Containing Lemon Flavour Granules

Lemon flavoured energy granules for filling the straws were prepared as for cherry flavoured granules in Example 1 . However, as shown in Table 3, the ingredients of the mixture contained lemon flavouring instead of cherry flavouring, and the colourings differed in order to produce yellow granules.

Table 3 - Ingredients list for lemon flavoured granules

Ingredients mg/straw % w/w Function

Vitamin Premix SRS 03

Contains: Vitamin

50 3.3

Vitamins B1 , B2, B3, B6, supplement

B12 and M-lnositol

Caffeine 88 5.9 CNS stimulant

Steviol glycosides 155 10.3 Sweetener

Flavour - Lemon 150 10.0 Flavouring

Tartaric Acid 410 27.3 Acidulant

Spheronization

Hydroxypropyl cellulose 95 6.3

aid

Maltodextrin 550 36.7 Binder

Colour - yellow 2 0.1 Colouring

Total 1500 100

Example 4

Drinking Straw Containing Lime Flavour Granules

Lime flavoured energy granules for filling the straws were prepared as for cherry flavoured granules in Example 1 . However, as shown in Table 4, the ingredients of the mixture contained lime flavouring instead of cherry flavouring, and the colourings differed in order to produce green granules.

Table 4 - Ingredients list for lime and mint flavoured granules

The invention hence provides drinking straw formulations of vitamins, optionally containing CNS stimulants, and methods of making the same.