CRYSTALLINE FORM II OF TETRAACETYLETHYLENEDIAMINE

[0001] The present invention relates to a new crystalline form of tetraacetylethylenediamine (TAED) and a method for its preparation. The present invention also relates to solid compositions comprising tetraacetylethylenediamine in this crystalline form, and in particular, to solid detergent or bleaching compositions.

[0002] Tetraacetylethylenediamine (CioHi6N ₂ 0 ₄ , IUPAC name: N,N ^' -l,2-Ethanediylbis(N- acetylacetamide); CAS registry number: 10543-57-4) is a well-known bleach activator which is mainly used in solid detergents or additives for laundry washing and dishwashing.

[0003] Solid detergent compositions typically incorporate "active oxygen" bleaching agents, such as sodium perborate, sodium percarbonate, sodium perphosphate, sodium persulphate and urea peroxide, which release hydrogen peroxide (in the form of perhydroxyl ion) during the wash. Whilst hydrogen peroxide is an efficient bleach above 60°C, the detergent composition usually includes a "bleach activator", such as tetraacetylethylenediamine, in order to obtain efficient bleaching at wash temperatures below 60°C.

[0004] The bleach activator "activates" hydrogen peroxide by reacting with it to generate another, more efficient, bleach. When, for example, tetraacetylethylenediamine (1, see Figure 1) is present in the wash liquor, the perhydroxyl ion reacts at the N-acetylacetamide moiety to hydrolyse the amide bond (in a process known as perhydrolysis,). The perhydrolysis produces peracetic acid (3, in the form of peracetyl ion) which is a fast-acting and more efficient bleach than hydrogen peroxide at temperatures below 60°C, for example at 40°C. The by-product of perhydrolysis is diacetylethylenediamine (2, DAED), which is biodegradable and removed with wash liquor to the environment.

[0005] Tetraacetylethylenediamine is commercially manufactured by acetylation of diacetylethylenediamine using acetic anhydride. Crystals of tetraacetylethylenediamine are obtained by filtering the reacted mixture after distillation of the by-product acetic acid (boiling point 118°C) and cooling to room temperature or lower.

[0006] One problem with the use of tetraacetylethylenediamine as a bleach activator arises from its low solubility (1.4 to 2.0 g/1 at 20°C) and low dissolution rate in water. A low availability of tetraacetylethylenediamine during room temperature wash or in (increasingly recommended) rapid wash cycles means inefficient cleaning by incomplete activation of perhydroxyl ion and wastage of tetraacetylethylenediamine .

[0007] The prior art has approached this problem by incorporating additional bleach activators which are more soluble than tetraacetylethylenediamine or by incorporating tetraacetylethylenediamine which has been agglomerated or coated with a non-ionic or anionic surfactant.

[0008] International patent application WO 2013/171492 Al, for example, discloses solid detergent compositions comprising tetraacetylethylenediamine and triacetylethylenediamine. These compositions are said to be more active than compositions comprising tetraacetylethylenediamine alone because of better solubility of triacetylethylenediamine in water as compared to tetraacetylethylenediamine .

[0009] International patent application WO 96/02601 Al, for example, discloses solid compositions comprising tetraacetylethylenediamine which are prepared by agglomerating with secondary (2,3) alkyl sulfate surfactants. These compositions are said to offer enhanced dispersion of tetraacetylethylenediamine in water and improved rates of perhydrolysis as compared to compositions formed by agglomeration of tetraacetylethylenediamine with non-ionic agglomerating agents.

[0010] However, the manufacture of detergent compositions comprising additional bleach activators or the agglomeration of tetraacetylethylenediamine with surfactants appears disadvantageous not only in that they require additional steps but also in that they introduce material inefficiencies.

[0011] For example, the preferred compositions described in WO 2013/171492 Al comprise in excess of three times the amount of triacetylethylenediamine as compared to tetraacetylethylenediamine because triacetylethylenediamine comprises only a single N-acetylacetamide moiety which is susceptible to perhydrolysis and so is inherently a less efficient activator than tetraacetylethylenediamine .

[0012] Another approach to the problem of poor solubility of tetraacetylethylenediamine in water is mentioned in WO 2013/171492 Al . This approach, which attempts to control of the size of crystals of tetraacetylethylenediamine, for example, by adopting a two-stage crystallisation procedure as disclosed in of European patent application EP 0 484 634 Al, is described as providing a rate of formation of peracetic acid which is inadequate at low wash temperatures such as 40°C or lower and during short washes. [0013] Notwithstanding this prior art, there still remains a need for improvement of the solubility of tetraacetylethylenediamine in water - particularly at temperatures below 40°C.

[0014] The present invention generally aims to address this need by providing a new crystalline form of tetraacetylethylenediamine.

[0015] The present inventors have found a new crystalline form of tetraacetylethylenediamine which has greater solubility in water and much faster dissolution rate than the known crystalline form of tetraacetylethylenediamine.

[0016] The new polymorph of tetraacetylethylenediamine is herein designated crystalline "Form Π" of tetraacetylethylenediamine. The hitherto known crystalline structure of tetraacetylethylenediamine (which corresponds to commercial tetraacetylethylenediamine) has now also to be considered a polymorph and is herein designated crystalline "Form I" of tetraacetylethylenediamine .

[0017] In a first aspect, therefore, the present invention comprises crystalline Form II of tetraacetylethylenediamine which has solubility in water (pH 7.0) at 20°C and atmospheric pressure above 2 g/1.

[0018] In a second aspect, the present invention comprises crystalline Form II of tetraacetylethylenediamine (TAED) which has absorptions in its Fourier Transform Infra-Red spectrum at wavenumbers 3013 cm ^"1 , 2979 cm ^"1 and 2945 cm ^"1 .

[0019] In a third aspect, the present invention comprises crystalline Form II of tetraacetylethylenediamine having an X-ray powder diffraction pattern measured using Cu (K _a ) radiation (154 nm) containing a reflective peak at a 2Θ value corresponding to a distance between parallel planes of atoms of 9.73A.

[0020] In this aspect, the crystalline Form II of tetraacetylethylenediamine (TAED) has an X-ray powder diffraction pattern further containing reflective peak at 2Θ values corresponding to the following distances between parallel planes of atoms: 4.97A, 4.90A, 4.81 A and 4.63A. [0021] Further, the crystalline Form II of tetraacetylethylenediamine (TAED) has an X-ray powder diffraction pattern also containing reflective peaks at 2Θ values corresponding to the following distances between parallel planes of atoms: 4.16A, 4.06Ά, 3.73A, 3.64A and 3.17A.

[0022] More particularly, the crystalline Form II of tetraacetylethylenediamine has an X-ray powder diffraction pattern as set out in Table 1.

[0023] The new crystalline form of tetraacetylethylenediamine may be prepared by melt crystallisation of crystalline Form I of tetraacetylethylenediamine. The melt crystallisation may be carried out by heating tetraacetylethylenediamine Form I to a temperature from about 20°C below to about 20°C above its melting point (152°C).

Table 1

[0024] In a third aspect, therefore, the present invention comprises a method for the preparation of crystalline Form II of tetraacetylethylenediamine, comprising heating crystalline Form I of tetraacetylethylenediamine to melting and allowing the molten tetraacetylethylenediamine to solidify to a solid mass by cooling to room temperature.

[0025] In a preferred embodiment, the method further comprises comminuting the solid mass whereby to form particles and/or particulates. The comminuting may, in particular, result in particle and/or particulate sizes of between 10 μιη to 20 μιη. [0026] The heating of crystalline Form I of tetraacetylethylenediamine may, in particular, comprise heating to a predetermined temperature from about 140°C to about 170°C (for example, to 145°C, 150°C, 155°C, 160°C or 165°C). The cooling preferably comprises cooling the molten tetraacetylethylenediamine at room temperature.

[0027] The predetermined temperature (and/or the rate and duration of the heating) may be selected so that the solid obtained on cooling contains at least 50%, for example 80%, 85%, 90%, 95% or 100% of crystalline Form II of tetraacetylethylenediamine.

[0028] The heating may be carried by heating crystalline Form I of tetraacetylethylenediamine in any suitable container. It may be effected by simply heating a crucible or by the use of an insulated or electrically heated vessel. Preferably, however, the heating is accompanied by agitation. Suitable equipment for effecting heating and agitation includes single screw and twin screw hot melt extruders, melt granulators, pan mills and high temperature kneaders. The use of such equipment enables crystalline Form II of tetraacetylethylenediamine to be manufactured by a continuous process or by a batch process.

[0029] It has rather surprisingly been found that the presence of additives does not divert or inhibit the formation of crystalline Form II of tetraacetylethylenediamine by the method. A large number of additives are tolerated and even additives which are otherwise well-known as co-crystal formers, such as urea and citric acid, do not affect or alter the formation of crystalline Form II of tetraacetylethylenediamine by this method.

[0030] In one embodiment, therefore, the heating of crystalline Form I of tetraacetylethylenediamine is carried out in the presence of one or more additives. Preferably, the one or more additives are suitable for formulation of a solid composition of crystalline Form II of tetraacetylethylenediamine, for example, as a detergent or bleaching composition.

[0031] The heating of crystalline Form I of tetraacetylethylenediamine may, in particular, be carried out in the presence of one or more additives selected from the group consisting of a surfactant or wetting agent, a pH modifier, a chelating agent, a stabilising agent, a diluent, a glidant, a binding agent, an effervescing agent, a disintegrating agent and a coating agent.

[0032] In a fourth aspect, the present invention comprises a solid composition comprising a bleach activator, which bleach activator comprises crystalline Form II of tetraacetylethylenediamine. [0033] The solid composition may take the form of granules, pellets, powder or tablet. It may, in particular, take the form of an effervescing tablet. The granules or powder may be provided with a sachet comprising a polymer which dissolves in water. A suitable sachet is described, for example, in United States patent application US 2013/0171264 Al .

[0034] The % weight of crystalline Form II of tetraacetylethylenediamine in the solid composition may vary depending on the intended use of the solid composition.

[0035] In general, the solid composition comprises at least 0.1% and preferably less than 20% by weight of crystalline Form II of tetraacetylethylenediamine. The solid composition may, in particular, comprise from 0.5% to 10% or from 0.5% to 8% or from 0.5% to 2.5% or less by weight of crystalline Form II of tetraacetylethylenediamine.

[0036] For solid detergent compositions, the % weight of crystalline Form II of tetraacetylethylenediamine is preferably from 1.25% to 2.5%.

[0037] For solid compositions intended to produce disinfectant or germicidal solutions, the % weight of crystalline Form II of tetraacetylethylenediamine is preferably from 4.0% to 5.0%.

[0038] For solid compositions intended to be used for bleaching and/or delignifying paper and pulp, the % weight of crystalline Form II of tetraacetylethylenediamine is preferably from 2.0% to 3.0%.

[0039] For solid compositions intended to be used for bleaching textiles prior to dyeing, the % weight of crystalline Form II of tetraacetylethylenediamine is preferably from 2.4% to 3.5%.

[0040] However, other % weights may be preferred when the solid composition includes one or more additional bleach activators. Suitable additional bleach activators may, for example, be selected from the group consisting of crystalline Form I of tetraacetylethylenediamine, triacetylethylenediamine, nonanoyloxybenzene sulphonate (NOBS) and dodecanoyloxybenzene sulphonate (DOBS).

[0041] In a preferred embodiment, the solid composition also comprises a bleaching agent such as sodium perborate, sodium percarbonate, sodium perphosphate, sodium persulphate or urea peroxide. [0042] In another preferred embodiment, the solid composition additionally comprises one or more of a surfactant or wetting agent. In this embodiment, the solid composition may be formulated as a detergent composition or for a disinfectant or germicidal solution by selection of an appropriate % weight of the one or more surfactant or wetting agent.

[0043] Alternatively or additionally, the solid composition may also comprise one or more additives selected from the group consisting of a pH modifier, a chelating agent, a stabilising agent, a diluent, a glidant, a binding agent, an effervescing agent, a disintegrating agent and a coating agent.

[0044] In one embodiment, the solid composition includes one or more of a surfactant or wetting agent selected from the group consisting of sodium lauryl sulfate, sodium laureth sulfate, potassium lauryl sulfate, sodium pareth sulfate, dioctyl sodium sulfosuccinate, perfluorobutanesulfonic acid, perfluorononanoic acid, perfluorooctane sulfonic acid, perfluorooctanoic acid, potassium lauryl sulfate, soap, soap substitute, sodium dodecyl sulfate, sodium dodecylbenzenesulfonate, sodium lauroyl sarcosinate, sodium myreth sulfate, sodium stearate, benzalkonium chloride, benzethonium chloride, bronidox, cetrimonium bromide, cetrimonium chloride, dimethyldioctadecylammonium chloride, lauryl methyl gluceth-10 hydroxypropyl dimonium chloride, tetramethylammonium hydroxide, cetomacrogol 1000, cetostearyl alcohol, cetyl alcohol, cocamide DEA, cocamide MEA, decyl glucoside, igepal CA-630, isoceteth-20, lauryl glucoside, monolaurin, narrow range ethoxylate, nonidet P-40, nonoxynol-9, nonoxynols NP-40, octaethylene glycol monododecyl ether, n-octyl β-d- thioglucopyranoside, octyl glucoside, oleyl alcohol, pentaethylene glycol monododecyl ether, poloxamer, poloxamer 407, polyglycerol polyricinoleate, polysorbate, polysorbate 20, polysorbate 80, sorbitan monostearate, sorbitan tristearate, stearyl alcohol, Triton X-100, amphiphile, chaps detergent, cocamidopropyl betaine, cocamidopropyl hydroxysultaine, egg lecithin, hydroxysultaine, lecithin and sodium lauroamphoacetate.

[0045] In another embodiment, the solid composition also includes one or more of a pH modifier selected from the group consisting of monopotassium phosphate, bicarbonate, monosodium phosphate and disodium phosphate, sulfamic acid, urea, citric acid, sodium/potassium silicate, sodium/potassium carbonate and sodium/potassium hydroxide.

[0046] In a further embodiment, the solid composition also includes one or more of a chelating agent selected from the group consisting of ethylenediaminetetraacetic acid, citric acid, sodium citrate, diethylene triamine pentaacetic acid, nitrilotriacetic acid, zeolite, condensed phosphate, acrylate-based polymers, sodium gluconate and phosphonates. [0047] In another embodiment, the solid composition also includes one or more of a stabiliser selected from the group consisting of carboxymethyl cellulose, polyvinylpyrrolidone, silicates, phosphates, proteases, amylases, lipases and cellulases.

[0048] In a further embodiment, the solid composition also includes one or more of a diluent selected from the group consisting of lactose, starch, sucrose, mannitol, sorbitol, cellulose, in particular, powdered cellulose, microcrystalline cellulose, inorganic materials including calcium phosphates such as anhydrous dibasic calcium phosphate, dibasic calcium phosphate, tribasic calcium phosphate and co- processed diluents.

[0049] In another embodiment, the solid composition also includes one or more of a glidant selected from the group consisting of magnesium stearate, aerosil (colloidal silicon dioxide), starch and talc.

[0050] In still another embodiment, the solid composition also includes one or more of a binder selected from the group consisting of saccharides and their derivatives, in particular, disaccharides such as sucrose, lactose; polysaccharides and their derivatives including starches, cellulose or modified cellulose such as microcrystalline cellulose and cellulose ethers such as hydroxypropyl cellulose; sugar alcohols such as xylitol, sorbitol or maltitol; proteins such as gelatin; synthetic polymers such as polyvinylpyrrolidone and polyethylene glycol binders. Preferred binders include gelatin, cellulose, cellulose derivatives, polyvinylpyrrolidone, starch, sucrose and polyethylene glycol and dry binders such as cellulose, methyl cellulose, polyvinylpyrrolidone and polyethylene glycol.

[0051] In a further embodiment, the solid composition also includes one or more of a disintegrant selected from the group consisting of cross-linked polymers such as cross-linked polyvinylpyrrolidone (for example, crospovidone), cross-linked sodium carboxymethyl cellulose (for example, croscarmellose sodium), and the modified starch sodium starch glycolate.

[0052] In still another embodiment, the solid composition also includes one or more of a coating agent selected from the group consisting of cellulose ether hydroxypropyl methylcellulose, hydropropylmethyl cellulose phthalate and hydropropylmethyl cellulose acetate succinate, cellulose acetate phthalate, shellac, corn protein zein or other polysaccharides, gelatine, polyvinyl alcohol. [0053] Of course, the selection of the one or more additives and their % weight for the solid composition will also depend on whether the solid composition is intended to be used as a detergent composition or for producing a disinfectant solution or a bleaching solution.

[0054] In a particular embodiment, the solid composition comprises TAED crystalline Form II and urea. The solid composition may be formulated as a powder or a tablet with or without a bleaching agent such as sodium percarbonate. It may also comprise one or more additives, for example, shellac, hydroxypropyl methyl cellulose acetate succinate (HPMCAS), sodium bicarbonate or sodium carbonate.

[0055] In this embodiment, the amount of TAED crystalline Form II in the solid composition may vary between 10% and 95%. The solid composition may, for example, comprise or be based on a 1 : 1 mixture (mole) of TAED crystalline Form II and urea. The percentage amount (by weight) of TAED crystalline Form II in the solid composition may, for example, be about 75%, 80% or 90% or, when a bleaching agent is present, about 20% or 30%.

[0056] The present invention is now described in more detail by reference to the following Examples and to the accompanying drawings in which:

Figure 1 is a scheme highlighting the chemical structure of tetraacetylethylenediamine and the perhydrolysis at the N-acetylacetamide moiety;

Figure 2 shows the powder X-ray diffraction patterns of crystalline Form II of tetraacetylethylenediamine and crystalline Form I of tetraacetylethylenediamine;

Figure 3 shows the FT-IR spectra of crystalline Form II of tetraacetylethylenediamine and crystalline Form I of tetraacetylethylenediamine;

Figure 4 shows Raman spectra of crystalline Form II of tetraacetylethylenediamine and crystalline Form I of tetraacetylethylenediamine;

Figure 5 shows DSC thermograms highlighting the melting points of crystalline Form II of tetraacetylethylenediamine and crystalline Form I of tetraacetylethylenediamine;

Figure 6 shows the powder X-ray diffraction patterns obtained by a variable temperature powder X-ray diffraction study of the conversion of crystalline Form I of tetraacetylethylenediamine to crystalline Form II of tetraacetylethylenediamine;

Figure 7 shows photographs highlighting the crystal habits of crystalline Form II of tetraacetylethylenediamine and crystalline Form I of tetraacetylethylenediamine; Figure 8 a graph showing the rate of dissolution of crystalline Form II of tetraacetylethylenediamine in water at 20°C as compared to the rate of dissolution of crystalline Form I of tetraacetylethylenediamine;

Figure 9 shows the powder X-ray diffraction pattern of crystalline Form II of tetraacetylethylenediamine after storage as compared to the X-ray diffraction pattern of crystalline Form

I of tetraacetylethylenediamine;

Figure 10 shows the powder X-ray diffraction patterns of a composition of crystalline Form

II of tetraacetylethylenediamine and urea (a) and of a composition of crystalline Form II of tetraacetylethylenediamine and citric acid (b) after storage as compared to the powder X-ray diffraction pattern of crystalline Form I of tetraacetylethylenediamine; and

Figure 11 is a graph showing the rate of dissolution of a solid composition of crystalline Form II of TAED and urea as compared to that of crystalline Form II of TAED and that of crystalline Form I of TAED.

Example 1 - Preparation of TAED Crystalline Form II

[0057] A glass crucible was charged with 500 mg of commercial tetraacetylethylenediamine (Form I, Sigma- Aldrich, UK) and the crucible heated on a hotplate to a temperature of 155°C. After 10 minutes of gentle stirring at 155°C with a glass rod, the tetraacetylethylenediamine formed a molten mass. The crucible was removed from the hotplate and allowed to cool to room temperature. The solid mass of tetraacetylethylenediamine obtained was transferred to a mortar and pestle and crushed (for about 5 minutes) to a fine powder.

Example 2 - Preparation of TAED Crystalline Form II

[0058] 100 g of commercial tetraacetylethylenediamine (Form I, Sigma Aldrich, UK) was hot- melt extruded from a 16 mm Pharmalab co-rotating twin screw extruder with screw length to diameter ratio 40: 1 (Thermo-Fisher Scientific, Karlsruhe, DE).

[0059] The extrusion was carried out without a die because the exudate was not completely molten but rather an agglomerated and compact mass.

[0060] The screw rotation speed was set to 100 rpm and tetraacetylethylenediamine fed at 0.3 kg/h feed rate to the barrel using a gravimetric twin screw feeder (Brabender, DE). The barrel was heated at a rate of 10°C per minute to a temperature profile shown in Table 2. Barrel zone 10 9 8 7 6 5 4 3 2

Temperature/°C 25 155 155 155 155 100 80 40 25

Table 2

[0061] The extruded material was allowed to cool to room temperature and the granular material so obtained comminuted using an IKA cutter mill equipped with a 1 mm sieve (for 5 minutes) to a fine powder (particle size 10 μιη to 20 μιη).

Powder X-Ray Diffraction Pattern for TAED Crystalline Form II

[0062] The powder (particle size 10 μιη to 20 μιη) from Examples 1 and 2 was analysed by powder X-ray diffraction (PXRD) using a Bruker D8 X-ray diffractometer (Coventry, UK) with wavelength 0.154 nm, Cu source, voltage 40 kV and filament emission 40 mA. The 2Θ scanning range was 2 to 30° and 0.01° steps used at 1 second time count. The scatter slit and the receiving slit were set at 0.2° and 0.1° respectively.

[0063] Figure 2 shows the powder X-ray diffraction pattern of the melt crystals (Form II) as compared to the pattern obtained using this apparatus for commercial tetraacetylethylenediamine (Form I; particle size 10 μιη to 20 μιη) and a library pattern for tetraacetylethylenediamine (Cambridge Structural Database).

[0064] The angle of reflection (2Θ), the corresponding distances (d) between parallel planes of atoms and the (%) relative intensity of the peaks for the two forms of tetraacetylethylenediamine are shown in Table 3.

21.84 4.06 9.06 25.36 3.51 9.72

23.84 3.73 72.37 26.88 3.31 100.00

24.44 3.64 15.93 28.88 3.09 9.45

28.12 3.17 55.16

Table 3

[0065] As may be seen, the pattern obtained for the melt crystals (Form II) is quite different to the pattern obtained for commercial tetraacetylethylenediamine and the library pattern (Form I; these latter two being identical). In particular, the pattern for the melt crystal shows an additional peak as compared to the other patterns for tetraacetylethylenediamine and includes a distinctive peak at 2Θ value 9.08° and a distinctive cluster of peaks between 2Θ values 17° and 19°.

[0066] The melt crystallisation of tetraacetylethylenediamine results in a new crystalline form of tetraacetylethylenediamine (Form II) as compared to the previously known (monoclinic) crystalline form of tetraacetylethylenediamine.

Fourier-Transform IR Spectrum of TAED Crystalline Form II

[0067] A Fourier-Transform Infra-Red spectroscopy by Attenuated Total Reflection (ATR) analysis of the powder of Examples 1 and 2 was performed using a Perkin Elmer 100 FT-IR spectrometer equipped GRAMS/AI software. A diamond crystal was used and absorptions were recorded at a constant crystal pressure over 16 scans in the wavelength range 600 cm ^"1 to 4000 cm ^"1 .

[0068] Figure 3 shows the spectrum recorded for the melt crystals (Form II) as compared to the spectrum recorded in the same way for commercial tetraacetylethylenediamine (Form I).

[0069] The melt crystal (Form II) shows characteristic absorptions at wavenumbers 3013 cm ^"1 , 2979 cm ^"1 , 2945 cm ^"1 , 1710 cm ^"1 , 1675 cm ^"1 , 1425 cm ^"1 , 1372 cm ^"1 , 1344 cm ^"1 , 1316 cm ^"1 , 1267 cm ^"1 , 1190 cm ^"1 , 1040 cm ^"1 , 1027 cm ^"1 , 974 cm ^"1 , 757 cm ^"1 and 696 cm ^"1 whereas commercial tetraacetylethylenediamine (Form I) shows characteristic absorptions at wavenumbers 1703 cm ^"1 , 1677 cm ^"1 , 1432 cm ^"1 , 1420 cm ^"1 , 1381 cm ^"1 , 1355 cm ^"1 , 1324 cm ^"1 , 1266 cm ^"1 , 1 190 cm ^"1 , 1038 cm ^"1 , 1024 cm ^"1 , 977 cm ^"1 and 761 cm ^"1 . [0070] The spectrum for crystalline Form II of tetraacetylethylenediamine is distinctly different from crystalline Form I in the stretching combinations at wavenumbers 3013 cm ^"1 , 2979 cm ^"1 and 2945 cm ^"1 .

Raman Spectrum for TAED Crystalline Form II

[0071] The Raman spectrum for the powder of Examples 1 and 2 was recorded using a ReniShaw Raman Microscope at laser wavelength 785 nm and half power. The laser was focused on the powder with a lOOx objective lens with an exposure rate of 10 times per second and spectral accumulation of 1 second. The backscattered radiation was collected (with removal of cosmic rays) by a high numerical aperture and passed through a confocal aperture to the detection system.

[0072] Figure 4 shows the Raman spectrum recorded for the melt crystals (Form II) as compared to that recorded in the same way for commercial tetraacetylethylenediamine (Form I).

[0073] The melt crystals (Form II) shows Raman shifts at wavenumbers 3011 cm ^"1 , 3000 cm ^"1 , 2967 cm ^"1 , 2943 cm ^"1 , 2939 cm ^"1 , 1723 cm ^"1 , 1681 cm ^"1 , 1458 cm ^"1 , 1428 cm ^"1 , 1374 cm ^"1 , 766 cm ^"1 and 649 cm ^"1 whereas commercial tetraacetylethylenediamine shows characteristic Raman shifts at wavenumbers 3023 cm ^"1 , 2977 cm ^"1 , 2946 cm ^"1 , 2937 cm ^"1 , 1700 cm ^"1 , 1683 cm ^"1 , 1427 cm ^"1 , 766 cm ^"1 and 649 cm ^"1 .

[0074] The Raman shifts for the melt crystals (Form II) generally show a tendency towards a lower wave number as compared to the Raman shifts for commercial tetraacetylethylenediamine (Form I).

Ή and ¹³ C NMR Spectra of TAED Crystalline Form II

[0075] Solution ¾ and ¹ C NMR spectra were recorded for the powder of Example 1 and commercial tetraacetylethylenediamine in deuterated chloroform using tetramethylsilane as internal standard on Jeol GX 270 MHz and ECA 600 MHz spectrometers.

[0076] The spectra (1H NMR/ppm: 2.40 (s, CH ₃ ), 3.77 (s, CH ₂ ); 13C NMR/ppm: 26.18 (s, CH ₃ ), 43.01 (s, C¾), and 173.44 (s, CO)) recorded for the melt crystals (Form II) were near identical to those for commercial tetraacetylethylenediamine (Form I).

Melting Point of TAED Crystalline Form II

[0077] A TA Instruments Q2000 differential scanning calorimeter (Crawley, UK) equipped with an RSC90 cooling unit was used to record thermograms for the melt crystals (Form II) and commercial tetraacetylethylenediamine (Form I). Indium metal was used for calibrating the instrument. 1.5 mg to 3 mg of the particular form was added to the aluminium pan and a second aluminium pan held empty as a reference. A heating rate of 10°C per minute or 20°C per minute was used and an inert environment maintained by nitrogen flow at 50 ml per minute.

[0078] Figure 5 shows the thermogram recorded for the melt crystals (Form II) as compared to that recorded for commercial tetraacetylethylenediamine (Form I).

[0079] As may be seen, the melt crystals (Form II) show a sharp melting point at 150.54°C whereas commercial tetraacetylethylenediamine (Form I) a minor melting endotherms at 142.92°C and a major melting endotherm at 152.47°C.

Conversion between TAED Crystalline Forms

[0080] The small difference in melting points of the melt crystals (Form II) and commercial tetraacetylethylenediamine (Form I) made it difficult to differentiate between the forms and, in particular, to study the conversion between forms.

[0081] The conversion can, however, be roughly monitored by variable temperature X-ray diffraction. A Bruker D8 diffractometer equipped with a temperature stage was used with scanning rate at 0.02Θ per 0.5 seconds and heating under nitrogen. A 20 mg sample of commercial tetraacetylethylenediamine (Form I; particle size 10 um to 20 μιη) was heated at 12°C per minute to 160°C and the pattern recorded at 10 minute intervals.

[0082] Figure 6 highlights the changes occurring in the sample when it is heated from room temperature to 160°C and the melt allowed to cool to room temperature. The pattern recorded before heating (A) corresponds to that of Form I of tetraacetylethylenediamine, the pattern recorded at 160°C (B) indicates the molten state of tetraacetylethylenediamine and the pattern recorded after the melt is allowed to cool to room temperature (C) corresponds to that of Form II of tetraacetylethylenediamine.

[0083] As may be seen, the patterns show complete conversion of commercial tetraacetylethylenediamine (Form I) to crystalline Form II of tetraacetylethylenediamine.

[0084] The conversion can also be roughly monitored by hot stage microscopy. The heating of a sample of commercial tetraacetylethylenediamine (Form I; 5 mgs) was examined on a hot stage microscope (Zeiss AxioPlan Mot Microscope) equipped with a Linkam TMS94 temperature controller. The sample was heated to 150°C at a heating rate of 2°C per minute and the resultant molten mass was cooled to room temperature at 2°C per minute.

[0085] The physical appearance of the melt crystals was of an agglomerated granular mass. Figure 7 shows a photograph of the sample taken after the melt has cooled to room temperature as compared to a photograph taken before the heating. As may be seen, the melt crystals (Form II) have an elongated rectangular (needle-like) crystal habit whereas commercial tetraacetylethylene (Form I) has a square (box-like) crystal habit.

[0086] Crystalline Form II of tetraacetylethylenediamine has a distinct crystal habit as compared to crystalline Form I of tetraacetylethylenediamine.

Stability of TAED Crystalline Form II

[0087] Powder samples of crystalline Form II of tetraacetylethylenediamine (prepared at a relative humidity less than 50%) were stored in sealed vessels at ambient temperature and pressure and at 40°C and 75% relative humidity. The samples were periodically analysed by powder X-ray diffraction to determine the presence or not of crystalline Form I of tetraacetylethylenediamine.

[0088] The samples stored for up to 2 months at ambient temperature and pressure and at 40°C and 75% relative humidity with no sign of conversion to Form I.

[0089] A powder sample of crystalline Form II of tetraacetylethylenediamine were also exposed to an environment of 90% relative humidity (at room temperature) for 13 hours using a Dynamic Vapour Sorption instrument. The sample was analysed by powder X-ray diffraction to determine the presence or not of crystalline Form I of tetraacetylethylenediamine.

[0090] Figure 8 shows that the patterns obtained during these studies. The sample stored at 40°C and 75% humidity (B) and the sample exposed to an environment of 90% relative humidity at room temperature (C) show no sign of crystalline Form I of tetraacetylethylenediamine (D).

[0091] Crystalline Form II of tetraacetylethylenediamine (A) appears stable to a high moisture environment. Example 3 - Solubility and Dissolution Rate of TAED Crystalline Form II in Water

[0092] The rate of dissolution of crystalline Form II of tetraacetylethylenediamine in water (500ml) was compared with the rate of dissolution of commercial tetraacetylethylenediamine (Form I) at 20°C and at 40°C using dissolution apparatus DS 8000 (Auto) LAB INDIA conforming to US Pharmacopeia (USP) II test.

[0093] The powder of Examples 1 and 2 was spun from a disc at 50 rpm and samples taken at intervals of 5 minutes to 30 minutes followed by 15 minute intervals to 60 minutes. The amount of dissolved tetraacetylethylenediamine was monitored by high performance liquid chromatography.

[0094] Figure 9 is a graph showing the dissolution of the melt crystals (Form II) as compared to the dissolution of commercial tetraacetylethylenediamine (Form I) under similar conditions. As may be seen, crystalline Form II of tetraacetylethylenediamine shows a much higher dissolution rate (pH 7.0) at both 20°C and 40°C as compared to crystalline Form I of tetraacetylethylenediamine.

[0095] The dissolution rate of crystalline Form II of tetraacetylethylenediamine appears to be an order magnitude higher than the dissolution rate of crystalline Form I of tetraacetylethylenediamine at 20°C.

[0096] A study to determine the intrinsic dissolution rate of the crystalline forms of tetraacetylethylenediamine was carried out using the same dissolution apparatus configured to USP Physical Test <1087>. The samples were prepared by pressing for 1 minute with an IR press (1 N/m ² ) using the 8 mm punch provided. The dissolution of the dies in deionised water (900 ml) was studied by sampling at 5 minute intervals to 30 minutes followed by 15 minute intervals to 60 minutes using high performance liquid chromatography described above.

[0097] The difference in the intrinsic dissolution rate of the two forms was found to be negligible this perhaps being due to poor penetration of the water to the die and/or conversion after penetration of water to the die of crystalline Form II of tetraacetylethylenediamine to crystalline Form I of tetraacetylethylenediamine .

[0098] Solubility measurements were made at the end of the dissolution rate study. Table 4 gives the solubility of Form II and Form I in water at various temperatures. As may be seen, the solubility of crystalline Form II of tetraacetylethylenediamine appears to be between two and three times greater than that of crystalline Form I of tetraacetylethylenediamine at 20°C. Temperature/°C Solubility/gl ¹

Form II Form I

20 1.27 0.51

30 1.69 1.20

40 2.24 1.98

Table 4

[0099] The ratio of solubility of crystalline Form II of tetraacetylethylenediamine to solubility of crystalline Form I of tetraacetylethylenediamine (at least three) appears, therefore, somewhat higher than that typically found for other polymorphic organic molecules (less than two).

Example 4 - Activation of Bleaching Agent by TAED Crystalline Form II in Water

[0100] The activation of bleaching agent by crystalline Form II of tetraacetylethylenediamine was determined by iodometric titration in accordance with the method described in international patent application WO2013/171492 Al .

[0101] 25g of a solid mixture of a 85% by weight IEC A* base detergent (Sigma Aldrich, UK), 10% by weight sodium percarbonate (Sigma Aldrich, UK) and 5% by weight crystalline Form II of tetraacetylethylenediamine was added to a beaker of 1 litre of deionised water with overhead stirring at 75 rpm. After 2 minutes, a 50 ml aliquot of the solution was removed from the beaker and added to a chilled (0°C) solution of 5 ml of 10% potassium iodide and 15 ml glacial acetic acid. The chilled solution was immediately titrated against 0.05M sodium thiosulphate using an appropriate indicator for iodine to determine the amount of iodine released by oxidation of iodide with peracetic acid.

[0102] The amount of thiosulphate used in the titre was related to the actual amount of peracetic acid released by tetraacetylethylenediamine on the basis that 2 moles of thiosulphate correlates to 1 mole of peracetic acid.

[0103] The amount of peracetic acid released by tetraacetylethylenediamine can be calculated by determining the number of moles of tetraacetylethylenediamine in the aliquot (by dividing gram weight by 20 x molecular weight) and multiplying by the number of moles of peracetic acid released by its hydrolysis by perhydroxyl ion (2 moles). [0104] In this experiment, the amount of peracetic acid released by crystalline Form II of tetraacetylethylenediamine at 20°C was calculated as 83 ppm.

[0105] In a similar experiment, the amount of peracetic acid released by crystalline Form I of tetraacetylethylenediamine was calculated as 41 ppm.

[0106] It may be seen, therefore, that crystalline Form II of tetraacetylethylenediamine is twice as good a bleach activator as compared to crystalline Form I of tetraacetylethylenediamine at 20°C.

Example 5 - Preparation of Solid Compositions of TAED Crystalline Form II

[0107] The method of Example 2 was carried out (at relative humidity less than 50%) as described above but with appropriate mixtures of commercial tetraacetylethylenediamine (Form I) and one or more additives.

[0108] The additives used included pH modifiers (urea, sulfamic acid and citric acid), a detergent surfactant (sodium lauryl sulphate), a coating agent (shellac), a disintegrating agent (Plasdone®) or a binding agent (polyethylene oxide, PEO).

[0109] The powder obtained after comminuting was examined for the presence of crystalline Form II of tetraacetylethylenediamine and crystalline Form I of tetraacetylethylenediamine using the Bruker D8 X-ray diffractometer (wavelength 0.154 nm, Cu source, voltage 40 kV and filament emission 40 mA) as described above.

[0110] The crystalline form of tetraacetylethylenediamine for each composition is reported in Table 5 (wherein the % weights are starting concentrations and the % weight of TAED is 100 minus the % weight of additive or additives).

[0111] As may be seen, only crystalline Form II of tetraacetylethylenediamine is found in all the compositions. Composition Additive/% weight j Crystalline Form of TAED \ TAED +

Urea 21 Form II only

Urea 34 Form II only

Urea 44 Form II only

Urea 12 Form II only

Sulfamic acid 30 Form II only

Sulfamic acid 46 Form II only

Shellac 5 Form II only

Citric acid 5 Form II only

Sodium lauryl sulphate 1 Form II only

Plasdone® 1 Form II only

Urea + PEO j 21+10 Form II only

Urea PI ) j 34+10 Form II only

Table 5

Stability of Solid Compositions of TAED Crystalline Form II

[0112] The stability of crystalline Form II of tetraacetylethylenediamine in the compositions obtained from Example 5 was examined in a similar manner as described above. Powder samples of the compositions were stored in sealed vessels at 40°C and relative humidity 75% and periodically analysed by PXRD to determine the presence or not of crystalline Form I of tetraacetylethylenediamine.

[0113] The crystalline form of tetraacetylethylenediamine after 2 months storage of these samples is reported in Table 6. Composition Additive/% weight j Crystalline Form of TAED \ TAED +

Urea 21 Form II only

Urea 34 Form II only

Urea 44 Form II only

Urea 12 Form II only

Sulfamic acid 30 Form I only

Sulfamic acid 46 Form I only

Shellac 5 Form I only

Citric acid 5 Form II only

Sodium lauryl sulphate 1 Form I only

Plasdone® 1 Form I only

Urea + PEO j 21+10 Form I only

Urea +PEO j 34+10 Form I only

Table 6

[0114] The samples comprising urea and citric acid as single additives showed no sign of crystalline Form I of tetraacetylethylenediamine whereas the other samples showed only crystalline Form I of tetraacetylethylenediamine.

[0115] The stability of crystalline Form II of tetraacetylethylenediamine in the compositions comprising urea and citric acid as single additive was found to extend to at least 6 months under these conditions.

[0116] Figures 10 (a) and (b) show respectively the powder X-ray diffraction pattern for a composition comprising 21% urea (79% crystalline Form II of tetraacetylethylenediamine) and the powder X-ray diffraction pattern for a composition comprising 5% citric acid (95% crystalline Form II of tetraacetylethylenediamine) obtained after 6 months storage under these conditions (C) as compared to the powder X-ray diffraction pattern of the composition on forming (B) and the powder X-ray diffraction patterns of crystalline Form II of tetraacetylethylenediamine (A) and crystalline Form I of tetraacetylethylenediamine (D).

Example 6 - Activation of Bleaching Agent by Solid Compositions of TAED Crystalline Form II

[0117] Solid compositions comprising TAED crystalline Form II and urea (Table 7) were prepared by a method similar to that of Example 2. The hot melt extrusions were carried out at a temperature 150°C using a 1 : 1 mixture (mole) of TAED crystalline Form I and urea. In two cases, an additional additive (shellac or hydroxypropyl methyl cellulose acetate succinate (HPMCAS)) was used with the mixture. A powder X-ray analysis of the powders obtained following the comminution showed that each composition comprised TAED in crystalline Form II.

[0118] The consumption of these solid compositions during peracid release from sodium percarbonate was compared with that of TAED crystalline Form II (without additive) and that of a proprietary formulation containing TAED crystalline Form I (Mykon TAED; available as granules from Warwick Chemicals, UK).

Table 7

[0119] In a first study, the solid compositions of Table 7 were mixed with sodium percarbonate (2.5 g sodium percarbonate per 1.0 g TAED crystalline Form II in the composition). Similar mixtures were prepared using TAED crystalline Form II and Mykon TAED.

[0120] Each mixture was added to 170 ml of water (pH 7.0) at 20°C with stirring (250 rpm). After stirring for 2 minutes, undissolved material was collected by filter paper (0.45 μιη), dried at room temperature and weighed. A similar experiment was made which collected undissolved material after 5 minutes.

[0121] In a second study, the solid compositions of Table 7 were mixed with sodium percarbonate (5.0g sodium percarbonate per 2.0 g TAED crystalline Form II in the composition). Similar mixtures were prepared using TAED crystalline Form II and Mykon TAED. [0122] Each mixture was added to 1.0 litre of water (pH 7.0) at 20°C with stirring (400 rpm). After stirring for 2 minutes, undissolved material was collected by filter paper, dried at room temperature and weighed. A similar experiment was made which collected undissolved material after 5 minutes.

[0123] Table 8 summarises the results of these studies. Note that powder X-ray diffraction showed the undissolved material to be, in each case, pure tetraacetylethylenediamine. As may be seen, the solid composition comprising urea and 2% shellac showed the least amount of undissolved material suggesting that peracid release from this composition is better than TAED crystalline form II and Mykon TAED.

Table 8

Example 7 -Rate of Dissolution of Solid Compositions of TAED Crystalline Form II in Water

[0124] The dissolution rate of the solid composition 1 of Table 7 in water (pH 7.0) at 30°C was compared with that of TAED crystalline Form II (without additive) and that of TAED crystalline Form I according to US Pharmacopeia (USP) II test.

[0125] The dissolution was monitored by analysing samples (ΙΟμΙ) taken at time intervals by high performance liquid chromatography. The analysis (and that of Example 3) was carried out on a CI 8 water symmetry column (4.6 mm x 250 mm; particle size 5 μιη) using acetonitrile and deionised water as the mobile phase (1 : 1 with 0.1% orthophosphoric acid) at a flow rate of 1 mL/minute. The column was equipped with a Waters e-2695 separation module integrated with a degasser and photodiode detector (PDA-2298) employing Empower 3 software for peak analysis at wavelength 260 nm.

[0126] Figure 11 shows the rate of solution of solid composition 1 (c) as compared to that of TAED crystalline Form II (b) and TAED Form I (a). The rate of solution of solid composition 1 is eight times higher than that of TAED crystalline Form 1.

Example 9 - Tablet Formation

[0127] The hot melt extrudates described in Example 2 and 6 were comminuted to a particle size of 500 μιη using a Kenwood Kmix mini roller compactor. The powders were subjected to tabletting by a RIMEK tablet compressing machined (Mini II MT, 12 station with 4D, 4B and 4BB tooling; Karnavati Engineering Ltd, India) using a 25 mm size punch.

[0128] Studies similar to those of Example 6 show that the amount of undissolved material is from the tablets of TAED crystalline Form II (with and without additive) are substantially similar to the amount of undissolved material from the corresponding powders.

[0129] Tablets comprising TAED crystalline Form II with sodium percarbonate were formed in a similar manner. The sodium percarbonate was reduced to similar particle size as the comminuted extrudates using an IKA cutter mill and mixed in the ratio 2.5: 1 sodium percarbonate: TAED crystalline Form II in extrudate.

[0130] The present invention provides a new form of crystalline tetraacetylethylenediamine (Form II) which has at least twice the solubility of commercial tetraacetylethylenediamine (Sigma Aldrich, UK) in water at 20°C and a dissolution rate which appears to be an order of magnitude higher than commercial tetraacetylethylenediamine .

[0131] It is of particular benefit to the manufacture of solid detergent compositions designed for low temperature or rapid cycle laundry processes as well as for solid compositions designed for fast- acting disenfection and paper or textile bleaching processes.

[0132] The new crystalline form (Form II) offers reduced wastage of tetraacetylethylenediamine across all kinds of laundry, disenfection and bleaching processes and may, therefore, be of benefit to the environment and/or enable cheaper manufacture of solid compositions for these processes by use of less tetraacetylethylenediamine. [0133] The new crystalline form (Form II) has good stability and can be easily manufactured from commercial tetraacetylethylenediamine using existing apparatus or equipment in a continuous or batch process and at minimal cost.

[0134] The method of the present invention is particularly advantageous in that it tolerates the presence of a wide range of additives including additives suitable for the formulation of solid detergent and bleaching compositions. It may, therefore, avoid an extra manufacturing step whilst still obtaining the benefit of enhanced laundry, disenfection and bleaching processes.

[0135] The present invention has been described generally and also by reference to the Examples and Drawings. The Examples and Drawings are merely illustrative of the general description and the scope of the present invention is not limited by the Examples and/or the Drawings but only by the accompanying claims.

[0136] Throughout the claims and the general description, the words "comprising" and "containing" and variations of them mean "including but not limited to" and do not exclude other components, integers or steps.