Magnesium diacetate x 4H2O and / or magnesium dichloride x 6H2O and / or magnesium sulfate x 7H2O and / or disodium sulfate x 10H2O and / or sodium thiosulfate x 5H2O and / or Na3PO4 x 12H2O and / or Na2HPO4 x 12H2O / 7H2O and / or sodium acetate x 3H2O as granulation aids

Abstract

The present invention relates to a powder mixture for preparing a granulate comprising as components at least a filler, or at least an active ingredient, or both, and magnesium diacetate x 4H2O and / or magnesium dichloride x 6H2O and / or magnesium sulfate x 7H2O and / or disodium sulfate x 10H2O and / or sodium thiosulfate x 5H2O and / or Na3PO4 x 12H2O and / or Na2HPO4 x 12H2O / 7H2O and / or sodium acetate x 3H2O as granulation aids. Optionally, components of the powder mixture to be granulated are binders, disintegrants and further conventional auxiliaries. It was an object of the present invention to provide a powder mix which is capable of granulation without the addition of liquid and in which the water for granulation is synergized in situ from Magnesium diacetate x 4H2O and / or Magnesium dichloride x 6H2O and / or Magnesium sulfate x 7H2O and / or Disodium sulfate x 10H2O and / or Sodium thiosulfate x 5H2O and / or Na3PO4 x 12H2O and / or Na2HPO4 x 12H2O / 7H2O and / or Sodium acetate x 3H2O. No additional drying step is required.

Description

[Technical field]

[0001] The present invention relates to magnesium diacetate x 4H2O and / or magnesium dichloride x 6H2O and / or magnesium sulfate x 7H2O and / or disodium sulfate x 10H2O and / or sodium thiosulfate x 5H2O and / or Na3PO4 x 12H2O and / or Na2HPO4 x 12H2O / 7H2O and / or sodium acetate x 3H2O as granulation aids. [Background technology]

[0002] In the technical field of granulation, especially wet granulation, the addition of water to the raw powder mixture to ensure particle growth by nucleation is always followed by a drying step at the end. Drying the wet granulate is expensive and requires resources such as energy, time, and machine utilization. As the market trend is moving from batch processes to continuous manufacturing, this drying step is often carried out by fluidized bed drying, which is expensive on the one hand because it requires more fluidized bed machines to ensure the continuity of the process, and only a semi-continuous process on the other hand. For a sustainable future, granulates are needed that are produced by processes that require less drying time and less energy to evaporate the moisture from the wet granulate. The wet granulation process of the present invention allows the wet granulation of large amounts of excipients and active ingredients that are not suitable for granulation due to their moisture sensitivity in the wet granulation processes currently used. This advantage, combined with the shorter process time, simplifies the product development and manufacturing process and meets the market trend of platform formulations. The platform formulation of the present invention is a powder mixture comprising excipients capable of synergizing during the granulation process, making a drying step unnecessary, in combination with a water-binding filler or water-binding active ingredient, reducing or preferably completely eliminating the need to add water as a granulation liquid. The present invention relates to a platform formulation that allows granulation by applying thermal energy, such as heat, infrared waves, or microwaves, to the powder mixture without adding any liquid. It has been shown that magnesium diacetate x 4H2O and / or magnesium dichloride x 6H2O and / or magnesium sulfate x 7H2O and / or disodium sulfate x 10H2O and / or sodium thiosulfate x 5H2O and / or Na3PO4 x 12H2O and / or Na2HPO4 x 12H2O / 7H2O and / or sodium acetate x 3H2O work extremely well as water-synthesizing excipients enabling granulation of the platform formulation (e.g. Na2·2H2O tartrate is not suitable for granulation at all). This application of energy makes it possible to take advantage of the free water for nucleation and recrystallization of salts resulting in a dry granulate. Unexpectedly, the resulting dry granulate is stable, non-hygroscopic and highly suitable for tableting.The resulting tablets have very high tensile strength. In further experiments, it could be shown that magnesium diacetate x 4H2O and / or magnesium dichloride x 6H2O and / or magnesium sulfate x 7H2O and / or disodium sulfate x 10H2O and / or sodium thiosulfate x 5H2O and / or Na3PO4 x 12H2O and / or Na2HPO4 x 12H2O / 7H2O and / or sodium acetate x 3H2O can also be used for continuous anhydrous granulation of active ingredients (e.g. acetylsalicylic acid, paracetamol, ibuprofen). The results were particularly surprising, since these active ingredients are known to be difficult to formulate. In addition, it can be used in any solid dosage form, such as tablets, pellets, or granules. Summary of the Invention [Problem to be solved by the invention]

[0003] Other potentially synergistic adjuvants, such as alum, calcium acetate, calcium chloride, carrageenan, corn starch, cyclocodextrine, kaolin, magnesium citrate, sodium citrate, sodium sulfite, raffinose, rice starch, tragacanth, trehalose, tricalcium citrate, wheat starch, and zinc sulfate, either do not form suitable granules with the desired increased particle size or the resulting granules have undesirably sticky, hygroscopic, or poorly compactable properties, and still other adjuvants, such as disodium sulfate x 10H2O, magnesium sulfate, The performance of magnesium diacetate x 4H2O and / or magnesium dichloride x 6H2O and / or magnesium sulfate x 7H2O and / or disodium sulfate x 10H2O and / or sodium thiosulfate x 5H2O and / or Na3PO4 x 12H2O and / or Na2HPO4 x 12H2O / 7H2O and / or sodium acetate x 3H2O was particularly surprising, since magnesium diacetate x 4H2O, magnesium dichloride x 6H2O and / or Na2HPO4 x 12H2O / 7H2O are indeed technically suitable as water-releasing excipients for granulation purposes, but are not applicable in any case to pharmaceutical dosage forms due to their taste or laxative effect on humans. Nevertheless, the granulates can be used in agricultural, cosmetic, medical or pharmaceutical preparations, food or feed, household detergents, cleaning agents, laundry detergents, dishwashing tablets, or mixtures thereof, optionally with a coating. [Means for solving the problem]

[0004] The present invention relates to a powder mixture for preparing a granulate comprising at least a filler, or at least an active ingredient, or both, and as granulates magnesium diacetate x 4H2O and / or magnesium dichloride x 6H2O and / or magnesium sulfate x 7H2O and / or disodium sulfate x 10H2O and / or sodium thiosulfate x 5H2O and / or Na3PO4 x 12H2O and / or Na2HPO4 x 12H2O / 7H2O and / or sodium acetate x 3H2O as components.

[0005] Optionally, the components of the powder mixture to be granulated are binders, disintegrants and further conventional auxiliaries. Of course, it is also possible to add at least one binder and / or at least one disintegrant and / or further conventional auxiliaries in dry form to the resulting granulate. The object of the present invention is to provide a powder mixture in which granulation is possible without adding liquid, but the water for granulation is dehydrated in situ from magnesium diacetate x 4H2O and / or magnesium dichloride x 6H2O and / or magnesium sulfate x 7H2O and / or disodium sulfate x 10H2O and / or sodium thiosulfate x 5H2O and / or Na3PO4 x 12H2O and / or Na2HPO4 x 12H2O / 7H2O and / or sodium acetate x 3H2O. No additional drying step is required.

[0006] It has thus been found that the powder mixture comprises: a) 10-95% by weight of at least one filler; b) 2.5-10% by weight of at least one binder; c) 2.5-20% by weight of magnesium diacetate x 4H2O and / or magnesium dichloride x 6H2O and / or magnesium sulfate x 7H2O and / or disodium sulfate x 10H2O and / or sodium thiosulfate x 5H2O and / or Na3PO4 x 12H2O and / or Na2HPO4 x 12H2O / 7H2O and / or sodium acetate x 3H2O; d) 0-7.5% by weight of at least one disintegrant; e) 0-85% by weight of at least one active ingredient and f) 0-5% by weight of further customary auxiliaries, the sum of components a) to e) being 100% by weight. Alternatively, the powder mixture comprises: a) 10-95% by weight of at least one filler; b) 2.5-10% by weight of at least one binder; c) 2.5-20% by weight of magnesium diacetate x 4H2O and / or magnesium dichloride x 6H2O and / or magnesium sulfate x 7H2O and / or disodium sulfate x 10H2O and / or sodium thiosulfate x 5H2O and / or Na3PO4 x 12H2O and / or Na2HPO4 x 12H2O / 7H2O and / or sodium acetate x 3H2O; d) 0-7.5% by weight of at least one disintegrant; e) 0-85% by weight of at least one active ingredient; and f) 0-5% by weight of further customary auxiliaries, the sum of the components a) to f) being 100% by weight.

[0007] The powder mixture comprises as component a) 0-98.5% by weight, preferably 7-97% by weight, more preferably 10-95% by weight of a filler. Suitable fillers are, for example, lactose (which may include modified lactose or anhydrous (NF) lactose), starch, in particular modified (pregelatinized) starch, native starch, or a mixture of both, calcium phosphates, in particular dicalcium phosphate, unmilled dicalcium phosphate, and anhydrous dicalcium phosphate, cellulose derivatives, cellulose, in particular microcrystalline cellulose, mannitol, sorbitol, etc. Of course, mixtures of different fillers can also be used.

[0008] Furthermore, the powder mixture comprises a binder as component b) in an amount of 0-15% by weight, preferably 1.5-10% by weight, more preferably 2.5-10% by weight of the total powder mixture. Suitable binders are water-soluble polymers and excipients, as well as film-forming excipients, such as polyvinylpyrrolidone, vinylpyrrolidone / vinyl acetate copolymers, polyvinyl alcohol, polyvinyl alcohol / polyethylene glycol graft copolymers, polyethylene glycol, ethylene glycol / propylene glycol block copolymers, hydroxypropylmethylcellulose, hydroxypropylcellulose, hydroxyethylcellulose, carrageenans, pectins, xanthans, lactose, sugar alcohols, and alginates. Naturally, mixtures of different binders can also be used.

[0009] An amount of 1.5-30% by weight, preferably 2.5-25% by weight, more preferably 2.5-20% by weight of magnesium diacetate x 4H2O and / or magnesium dichloride x 6H2O and / or magnesium sulfate x 7H2O and / or disodium sulfate x 10H2O and / or sodium thiosulfate x 5H2O and / or Na3PO4 x 12H2O and / or Na2HPO4 x 12H2O / 7H2O and / or sodium acetate x 3H2O is used as granulation aid as component c) of the powder mixture. It is possible to use as constituents magnesium diacetate x 4H2O and / or magnesium dichloride x 6H2O and / or magnesium sulfate x 7H2O and / or disodium sulfate x 10H2O and / or sodium thiosulfate x 5H2O and / or Na3PO4 x 12H2O and / or Na2HPO4 x 12H2O / 7H2O and / or sodium acetate x 3H2O with an average particle size of about 500 μm, but it has been observed that magnesium diacetate x 4H2O and / or magnesium dichloride x 6H2O and / or magnesium sulfate x 7H2O and / or disodium sulfate x 10H2O and / or sodium thiosulfate x 5H2O and / or Na3PO4 x 12H2O and / or Na2HPO4 x 12H2O / 7H2O and / or sodium acetate x 3H2O with an average particle size d(0.5) of less than 300 μm are particularly suitable for improving the mixing behavior of the powder mixture.

[0010] Furthermore, the powder mixture may contain a disintegrant as component d) in an amount of 0-12.5% ​​by weight, preferably 0-10% by weight, more preferably 0-7.5% by weight. Suitable disintegrants are crosslinked polyvinylpyrrolidone, croscarmellose, sodium starch glycolate, which according to the invention also refer to their sodium and potassium salts. Furthermore, sodium carboxymethyl starch is suitable. L-hydroxypropylcellulose (preferably with 5-16% hydroxypropoxy groups) is likewise suitable. Naturally, mixtures of different disintegrants can also be used.

[0011] Optionally, the powder mixture may further comprise 0-98.5% by weight, preferably 0-90% by weight, more preferably 0-85% by weight of an active ingredient as component e) of the powder mixture.

[0012] In principle, any active ingredient can be employed as the active ingredient.

[0013] Examples of suitable active ingredients include analgesics and anti-inflammatory drugs such as fentanyl, indomethacin, ibuprofen, naproxen, diclofenac, diclofenac sodium, fenoprofen, acetylsalicylic acid, ketoprofen, nabumetone, paracetamol, piroxicam, meloxicam, tramadol, and COX-2 inhibitors such as celecoxib and rofecoxib; antiarrhythmic drugs such as procainamide, quinidine, and verapamil; antibacterial and antiprotozoal drugs such as amoxicillin, ampicillin, benzathine penicillin, benzylpenicillin, cefaclor, cefadroxil, cefprozil, cefuroxime axetil, cephalexin, chloramphenicol, chloroquine, ciprofloxacin, clarithromycin, cla[1]vulanic acid, acid, clindamycin, doxycycline, erythromycin, flucloxacillin sodium, halofantrine, isoniazid, kanamycin sul[1]phate, lincomycin, mefloquine, minocycline, nafcillin sodium, nalidixic acid, neomycin, nortloxacin, ofloxacin, oxa[1]cillin, phenoxymethylpenicillin potassium, pyrimethaminesulfadoxime, and streptomycin; anticoagulants such as warfarin; antidepressants such as amitriptyline, amoxapine, butriptyline, clomipramine, desipramine, dothiepin, doxepin, flucloxacillin, fluox ... fluox[1]etine, reboxetine, amineptine, selegiline, gepirone, imipramine, lithium carbonate, mianserin, milnacipran, nortriptyl[1]ine, paroxetine, sertraline, and 3-[2-[3,4-dihydrobenzofuro[3,2-c]pyridin-2(1H)-yl]ethyl]-2-methyl-4H-pyrido[1,2-a]py[1]rimidin-4-one; antidiabetic drugs, such as glibenclamide, and metformin;Antiepileptics such as Carbamazepine, Clonazepam, Ethosuximide, Gabapentin, Lamotrigine, Levetiracetam, Phenobarbitone, Phenytoin, Primidone, Tiagabine, Topiramate, Valpromide, and Vigabatrin; Antifungals such as Amphotericin, Clotrimazole, Econazole, Fluconazole, Flucytosine, Griseofulvin, Itraconazole, Ketoconazole, Miconazole Nitrate, Nystatin, Terbinafine, and Voriconazole; Antihistamines such as Astemizole, Cinnarizine, Cyproheptane, and Cyclohexanone; antihypertensives such as captopril, enalapril, ketanserin, lisinopril, minoxidil, prazosin, ramipril, reserpine, terazosin, and telmisartan; antimuscarinic agents such as atropine sulfate, and hyoscine; antitumor and antimetabolites such as platinum compounds, e.g., cisplatin ... and carboplatin; taxanes, such as paclitaxel and docetaxel; tecans, such as camptothecin, irinotecan, and topotecan; vinca alkaloids, such as vinblastine, vindesine, vincristine, and vinorelbine; nucleoside derivatives and folate antagonists, such as 5-fluorouracil, capecitabine, gemcitabine, mercaptopurine, thioguanine, cladribine, and methotrexate; alkylating agents such as nitrogen mustards, such as cyclophosphamide, chlorambucil, thiolmethine (chi ormethine, ifosphamide, melphalan, or nitrosoureas such as carmustine, lomustine, or other alkylating agents such as busulfan, dacarbazine, procarbazine, thiotepa; antibiotics such as daunorubicin, doxorubicin, idarubicin, epirubicin, bleomycin, dactinomycin, and mito[1]mycin; podophyllotoxin derivatives such as etoposide, and teniposide; famesyl transferase inhibitors;anthraquinone derivatives such as mitoxantrone; antimigraine drugs such as arniditan, naratriptan, and sumatriptan; antiparkinsonian drugs such as bromocriptine mesylate, levodopa, and selegiline; antipsychotics, hypnotics, and sedatives such as alprazolam, buspirone, chlordiazepoxide, chlorpromazine, clozapine, diazepam, flupentixol, fluphenazine, flurazepam, 9-hydroxyrisperidone, lorazepam, mazapertine, orthopedic drugs such as azepam, ... olan[1]zapine, oxazepam, pimozide, pipamperone, piracetam, promazine, risperidone, selfotel, seroquel, sertindole, sulpir[1]ide, temazepam, thiothixene, triazolam, trifluperidol, ziprasidone, and zolpidem; antistroke agents such as lubelozole, lubelozole oxide, riluzole, aptiganel, eliprodil, and remacemide; antitussives such as dextromethorphan and levodroside. Propidine; antiviral drugs such as acyclovir, ganciclovir, loviride, tivirapine, zidovudine, lamivudine, zidovudine / lamivudine, didano[1]sine, zalcitabine, stavudine, abacavir, lopinavir, amprenavir, nevirapine, efavirenz, delavirdine, indinavir, nelfinavir, ritonavir, saquinavir, adefovir, and hydroxyurea; beta-adrenergic receptor blockers such as atenolol, carvedilol, metoprolol, nevirapine, borole, and propanolol; cardiac inotropes such as amrinone, digitoxin, digoxin, and milrinone; corticosteroids such as beclomethasone dipropionate, betamethasone, budesonide, dexamethasone, hydrocorti[1]sone, methylprednisolone, prednisolone, prednisone, and triamcinolone; antiseptics such as chlorhexidine; diuretics such as acetazolamide, furosemide, hydrochlorothiazide, and isosorbide; enzymes;Gastrointestinal drugs, such as cimetidine, cisapride, clebopride, diphenoxylate, domperidone, famotidine, lanso[1]prazole, loperamide, loperamide oxide, mesalazine, metoclopramide, mosapride, nizatidine, norcisapride, olsala[1]zine, omeprazole, pantoprazole, perprazole, prucalopride, rabeprazole, la nitidine, ridogrel, and sulfasalazine; hemostatic agents such as aminocaproic acid; HIV protease inhibitor compounds such as ritonavir, lopinavir, indinavir, saquinavir, tipranavir; lipid regulating agents such as atorvastatin, fenofibrate, fenofibric acid, lovastatin, pravastatin, probucol, and simv[1]astatin; local anesthetics such as benzocaine, and lignocaine; opioid analgesics, such as buprenorphine, codeine, dextromoramide, dihydrocodeine, hydrocodone, oxycodone, and morphine; parasympathomimetics and anti-dementia drugs, such as eptastigmine, galantamine, metrifonate, mil[1]ameline, neostigmine, physostigmine, tacrine, donepezil, rivastigmine, sabcomeline, talsaclidine, quizacr ... nomeline, me[1]mantine, and lazabemide; peptides and proteins, such as antibodies, becaplermin, cyclosporine, tacrolimus, erythropoietin, immunoglobulins, and insulin; sex hormones, such as estrogens: conjugated estrogens, ethinyl estradiol, mestranol, estradiol, estriol, oestro[1]ne; progestogens;Chlormadinone acetate, cyproterone acetate, 17-deacetylnorgestimate, desogestrel, dienogest, dydrogesterone, ethynodiol diacetate, gestodene, 3-ketodesogestrel, levonorgestrel, lynestrenol, medroxyprogesterone acetate, megestrol, norethindrone, norethindrone acetate, norethisterone, norethisterone acetate, norethyn[1]odrel, norgestimate, norgestrel, norgestrienone, progesterone, and kingestanoic acetate. stimulants such as sildenafil, vardenafil; vasodilators such as amlodipine, buflomedil, amyl nitrite, diltiazem, dipyridamole, glyceryl trinitrate, isosorbide din[1]itrate, lidoflazine, molsidomine, nicardipine, nifedipine, oxpentifylline, and pentaerythritol tetranitrate; N-oxides thereof, pharma- ceutical acceptable acid or base addition salts thereof, stereochemical isomers thereof, and polymorphs thereof.

[0014] Mixtures of active ingredients may also be used.

[0015] Furthermore, the powder mixture may comprise further conventional auxiliaries as component f) in an amount of 0-15% by weight, preferably 0-10% by weight, more preferably 0-5% by weight. Suitable further conventional auxiliaries are selected from flowing agents, acidifiers, sweeteners, flavorings, taste enhancers, thickeners, and / or surfactants.

[0016] The invention also relates to a process for producing granulates from a powder mixture comprising as components at least a filler or at least an active ingredient or both. For this purpose, the powder mixture to be granulated may also contain a binder and / or a disintegrant, and optionally further conventional auxiliaries, the granulation being carried out with the addition of granulation auxiliaries which are magnesium diacetate x 4H2O and / or magnesium dichloride x 6H2O and / or magnesium sulfate x 7H2O and / or disodium sulfate x 10H2O and / or sodium thiosulfate x 5H2O and / or Na3PO4 x 12H2O and / or Na2HPO4 x 12H2O / 7H2O and / or sodium acetate x 3H2O. The powder mixture is granulated by inducing at least a partial dehydration of the crystal water of magnesium diacetate x 4H2O and / or magnesium dichloride x 6H2O and / or magnesium sulfate x 7H2O and / or disodium sulfate x 10H2O and / or sodium thiosulfate x 5H2O and / or Na3PO4 x 12H2O and / or Na2HPO4 x 12H2O / 7H2O and / or sodium acetate x 3H2O while mixing. The preferred temperature of the powder mixture is raised to a temperature of 35°C to 120°C, more preferably to a temperature of 40°C to 100°C. The thermal heat for the temperature increase is generated by a heating device. According to the present invention, any form of heating device can be used, with microwave radiation sources, infrared heaters, infrared dryers, high shear mixers, and extruders being preferred, and with twin screw extruders being most preferred.

[0017] The invention is further illustrated by the following figures and examples. [Brief description of the drawings]

[0018] [Figure 1] Standard screw configurations for extruders. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0019] Working Example: Analysis method The particle size distributions (d(0.1), d(0.5), d(0.9)) of the powder mixture constituents and of the produced granulates were determined using a Malvern Mastersizer 2000 (FAMalvern Panalytical). The granulates in dry powder form were measured at a dispersion air pressure of 1.0-2.0 bar for approximately 30-60 seconds.

[0020] Granulation using an extruder To granulate the powder mixture, each component was weighed and mixed briefly by hand. This premix was sieved through a 800 μm steel sieve and then mixed for 10 minutes using a tumble blender to obtain what is referred to below as "raw material (mixture)". This raw material (mixture) was granulated using a twin-screw extruder (Thermo Fisher Scientific, 11 mm) with the following parameters (barrel L / D ratio 40:1) and the screw configuration shown in Figure 1.

[0021] [Table 1]

[0022] The granulate exiting the extruder is directly further processed by a milling process to give a good uniform particle size distribution, or more preferably a sieving process, to obtain a granulate of a particle size particularly suitable for tableting.

[0023] Tablet forming: Sieving of the granulate preparation was carried out using a vibrating sieve shaker (Retsch-AS200) with a mesh size of 1000 μm at an amplitude of 1.0 mm / g for approximately 2 minutes.

[0024] The sieved <1000 μm fraction was mixed with additional 1.0% sodium stearyl fumarate in a tumble blender for about 2 minutes. This blend was further used for tableting.

[0025] Tableting was performed on a multi-functional R&D press (Medelpharm-Styl'one Evo) equipped with a 10 mm biplane punch. Compaction pressures varied from 50 MPa to 400 MPa.

[0026] Tablets were analyzed (10 tablets per test) using a semi-automatic tablet hardness tester (Sotax-SmartTest50). Tensile strength was measured according to USP <1217> It can be calculated according to

[0027] [Table 2]

[0028] [Table 3]

[0029] [Table 4]

[0030] [Table 5]

Claims

1. A powder mixture for making a granulate, comprising: a. 0 to 98.5 wt. % of at least one filler; b. 0-15 wt. % of at least one binder; c. 1.5 to 30% by weight of magnesium diacetate x 4H ２ O and / or magnesium dichloride x 6H ２ O and / or magnesium sulfate x 7H ２ O and / or disodium sulfate x 10H ２ O and / or sodium thiosulfate x 5H ２ O and / or Na ３ P.O. ４ x 12H ２ O and / or Na ２ H.P.O. ４ x 12H ２ 0 / 7H ２ O and / or sodium acetate x 3H ２ O. d. 0-12.5% ​​by weight of at least one disintegrant; e. 0 to 98.5% by weight of at least one active ingredient Including, A powder mixture in which the sum of the components a. to e. is 100% by weight; or A powder mixture for making a granulate, comprising: a. 0 to 98.5 wt. % of at least one filler; b. 0-15 wt. % of at least one binder; c. 1.5 to 30% by weight of magnesium diacetate x 4H ２ O and / or magnesium dichloride x 6H ２ O and / or magnesium sulfate x 7H ２ O and / or disodium sulfate x 10H ２ O and / or sodium thiosulfate x 5H ２ O and / or Na ３ P.O. ４ x 12H ２ O and / or Na ２ H.P.O. ４ x 12H ２ 0 / 7H ２ O and / or sodium acetate x 3H ２ O. d. 0-12.5% ​​by weight of at least one disintegrant; e. 0-98.5% by weight of at least one active ingredient; f. 0 to 15% by weight of further conventional auxiliaries Including, A powder mixture, wherein the sum of said components a. to f is 100% by weight.

2. A powder mixture for making a granulate, comprising: a. 7 to 97 weight percent of at least one filler; b. 1.5 to 10 wt. % of at least one binder; c. 1.5 to 25% by weight of magnesium diacetate x 4H ２ O and / or magnesium dichloride x 6H ２ O and / or magnesium sulfate x 7H ２ O and / or disodium sulfate x 10H ２ O and / or sodium thiosulfate x 5H ２ O and / or Na ３ P.O. ４ x 12H ２ O and / or Na ２ H.P.O. ４ x 12H ２ 0 / 7H ２ O and / or sodium acetate x 3H ２ O. d. 0-10% by weight of at least one disintegrant; e. 0-90% by weight of at least one active ingredient Including, A powder mixture in which the sum of the components a. to e. is 100% by weight; or A powder mixture for making a granulate, comprising: a. 7 to 97 weight percent of at least one filler; b. 1.5 to 10 wt. % of at least one binder; c. 1.5 to 25% by weight of magnesium diacetate x 4H ２ O and / or magnesium dichloride x 6H ２ O and / or magnesium sulfate x 7H ２ O and / or disodium sulfate x 10H ２ O and / or sodium thiosulfate x 5H ２ O and / or Na ３ P.O. ４ x 12H ２ O and / or Na ２ H.P.O. ４ x 12H ２ 0 / 7H ２ O and / or sodium acetate x 3H ２ O. d. 0-10% by weight of at least one disintegrant; e. 0-98.5% by weight of at least one active ingredient; f. 0-10 wt. % of further conventional auxiliaries Including, A powder mixture, wherein the sum of said components a. to f is 100% by weight.

3. A powder mixture for making a granulate, comprising: a. 10 to 95 weight percent of at least one filler; b. 2.5 to 10 wt. % of at least one binder; c. 2.5 to 20% by weight of magnesium diacetate x 4H ２ O and / or magnesium dichloride x 6H ２ O and / or magnesium sulfate x 7H ２ O and / or disodium sulfate x 10H ２ O and / or sodium thiosulfate x 5H ２ O and / or Na ３ P.O. ４ x 12H ２ O and / or Na ２ H.P.O. ４ x 12H ２ 0 / 7H ２ O and / or sodium acetate x 3H ２ O. d. 0-7.5% by weight of at least one disintegrant; e. 0-85% by weight of at least one active ingredient; A powder mixture in which the sum of the components a. to e. is 100% by weight; or A powder mixture for making a granulate, comprising: a. 10 to 95 weight percent of at least one filler; b. 2.5 to 15 wt. % of at least one binder; c. 2.5 to 20% by weight of magnesium diacetate x 4H ２ O and / or magnesium dichloride x 6H ２ O and / or magnesium sulfate x 7H ２ O and / or disodium sulfate x 10H ２ O and / or sodium thiosulfate x 5H ２ O and / or Na ３ P.O. ４ x 12H ２ O and / or Na ２ H.P.O. ４ x 12H ２ 0 / 7H ２ O and / or sodium acetate x 3H ２ O. d. 0-7.5% by weight of at least one disintegrant; e. 0-85% by weight of at least one active ingredient; f. 0 to 15 wt. % of further conventional auxiliaries; A powder mixture, wherein the sum of said components a. to f is 100% by weight.

4. Magnesium diacetate x 4H ２ O and / or magnesium dichloride x 6H ２ O and / or magnesium sulfate x 7H ２ O and / or disodium sulfate x 10H ２ O and / or sodium thiosulfate x 5H ２ O and / or Na ３ P.O. ４ x 12H ２ O and / or Na ２ H.P.O. ４ x 12H ２ 0 / 7H ２ O and / or sodium acetate x 3H ２ The powder mixture according to any one of claims 1 to 3, wherein the average particle size d(0.5) of the O particles is less than 300 μm.

5. A method for producing a granulate from a powder mixture comprising at least a filler or at least an active ingredient or both, and optionally at least one binder, and / or optionally at least one disintegrant, and / or optionally at least one further customary auxiliary, wherein the granulation is carried out using magnesium diacetate x 4H ２ O and / or magnesium dichloride x 6H ２ O and / or magnesium sulfate x 7H ２ O and / or disodium sulfate x 10H ２ O and / or sodium thiosulfate x 5H ２ O and / or Na ３ P.O. ４ x 12H ２ O and / or Na ２ H.P.O. ４ x 12H ２ 0 / 7H ２ O and / or sodium acetate x 3H ２ The temperature of the mixture is increased to 50° C. or higher, and the magnesium diacetate×4H ２ O and / or magnesium dichloride x 6H ２ O and / or magnesium sulfate x 7H ２ O and / or disodium sulfate x 10H ２ O and / or sodium thiosulfate x 5H ２ O and / or Na ３ P.O. ４ x 12H ２ O and / or Na ２ H.P.O. ４ x 12H ２ 0 / 7H ２ O and / or sodium acetate x 3H ２ The method is carried out while mixing by inducing syneresis of at least a portion of the water of crystallization of O to granulate the powder mixture.

6. 6. The method of claim 5, wherein the temperature of the powder mixture to be granulated is raised to 35-120°C.

7. 7. The method of claim 5 or 6, wherein the temperature of the powder mixture is increased by a heating device.

8. 8. The method of claim 7, wherein the heating device is a microwave radiation source, or an infrared dryer, or an infrared heater, or a high shear mixer, or an extruder, or a combination thereof.

9. 9. The method according to claim 8, wherein the heating device is an extruder, in particular a twin-screw extruder.

10. A method according to any one of claims 5 to 9, wherein the granulate produced is directly milled or sieved.

11. The method according to any one of claims 5 to 10, wherein the granulate is produced continuously.

12. Granulate obtainable by the process according to any one of claims 5 to 11 for tableting or for filling capsules.

13. 13. A food or feed, household detergent, cleaning agent, laundry detergent, dishwashing tablet, or cosmetic, or agricultural, or medical, or pharmaceutical preparation, or a mixture thereof, comprising a granulate according to claim 12.

14. Diacetate x 4H as a component in the powder mixture as a granulation aid ２ O and / or magnesium dichloride x 6H ２ O and / or magnesium sulfate x 7H ２ O and / or disodium sulfate x 10H ２ O and / or sodium thiosulfate x 5H ２ O and / or Na ３ P.O. ４ x 12H ２ O and / or Na ２ H.P.O. ４ x 12H ２ 0 / 7H ２ O and / or sodium acetate x 3H ２ Use of O.

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