Potassium Sodium Tartrate as a Granulation Aid

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 the granulation aid potassium sodium tartrate tetrahydrate (PST). Optionally, the 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 mixture that can be granulated without adding liquid, and in which the water for granulation is dehydrated in situ from the PST. No additional drying step is required.

Description

[Technical field]

[0001] The present invention relates to potassium sodium tartrate as a granulation aid. [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 containing an excipient that allows water release during the granulation process, making a drying step unnecessary, in combination with a water-binding filler or water-binding active ingredient, which reduces or preferably completely eliminates 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 the addition of any liquid. It has been shown that potassium sodium tartrate tetrahydrate (PST) has excellent performance as a water-release excipient that allows granulation of the platform formulation (e.g., sodium tartrate). 2 2H 2(O is not suitable for granulation at all). PST dehydrates its water of hydration by application of the energy input method described above. This application of energy makes it possible to take advantage of the free water for nucleation and recrystallization of the salt resulting in a dry granulate. It was unexpected that the resulting dry granulate is stable, non-hygroscopic and very suitable for tableting. The resulting tablets have very high tensile strength. In further experiments it could be shown that PST can also be used for the continuous anhydrous granulation of active ingredients (e.g. acetylsalicylic acid, paracetamol, ibuprofen). This result was particularly surprising since these active ingredients are known to be difficult to formulate. PST is also uncritical for oral use, its daily toxic intake is very low at 3 g / kg (Kassaian JM, Ullmann's Encyclopedia Vol. 35, p. 677) and it can be used in any solid dosage form such as tablets, pellets or granules. Furthermore, it is not dangerous for long-term toxicity. [Prior art documents] [Non-patent literature]

[0003] [Non-Patent Document 1] Kassaian JM, Ullmann's Encyclopedia Vol.35, p.677 Summary of the Invention [Problem to be solved by the invention]

[0004] The performance of PST was particularly surprising since other potentially water-repelling auxiliaries such as alum, calcium acetate, calcium chloride, carrageenan, corn starch, cyclocodextrine, kaolin, magnesium acetate, magnesium citrate, magnesium sulfate, sodium citrate, sodium sulfate, sodium sulfite, trisodium phosphate, dibasic sodium phosphate, raffinose, rice starch, sodium acetate, tragacanth, trehalose, tricalcium citrate, wheat starch, and zinc sulfate either do not form suitable granulates with the desired increased particle size or the resulting granulates have undesirably sticky, hygroscopic, or poorly compactable properties, and further auxiliaries such as sodium sulfate, magnesium sulfate, magnesium chloride, and dibasic sodium phosphate are indeed technically suitable as water-repelling excipients for granulation purposes, but are in any case not applicable to pharmaceutical dosage forms due to their taste or laxative effect on humans. [Means for solving the problem]

[0005] 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 PST as a granulation aid. Optionally, the components of the powder mixture to be granulated are a binder, a disintegrant, 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 which allows granulation without adding liquid, but in which the water for granulation is dehydrated in situ from the PST. No additional dying step is required. Thus, it has 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 PST, d) 0-7.5% by weight of at least one disintegrant, and e) 0-85% by weight of at least one active ingredient, the sum of the components a) to e) being 100% by weight, or alternatively, it has 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 PST, 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.

[0006] 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.

[0007] 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.

[0008] Potassium sodium tartrate tetrahydrate (PST) in an amount of 1.5-30% by weight, preferably 2.5-25% by weight, more preferably 2.5-20% by weight, is used as a granulation aid as component c) of the powder mixture. It is possible to use PST with a particle size of about 500 μm d(0.5) 504 μm) as a component, but it has been observed that PST with a mean particle size d(0.5) of less than 300 μm is particularly suitable for improving the mixing behavior of the powder mixture.

[0009] 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.

[0010] 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.

[0011] In principle, any active ingredient can be employed as the active ingredient.

[0012] 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 Voriconazole. 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, norethindrone, norethindrone acetate, norethisterone, norethisterone acetate, norethynodrel, norgestimate, norgestrel, norgestrienone, progesterone and quingestanol acetate, ethynodiol diacetate, gestodene, 3-ketodesogestrel, levonorgestrel, lynestrenol, medroxyprogesterone acetate, megestrol, norethindrone, norethindrone acetate, norethisterone, norethisterone acetate, norethyn[1]odrel l), norgestimate, norgestrel, norgestrienone, progesterone, and quingestanol 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.

[0013] Mixtures of active ingredients may also be used.

[0014] 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.

[0015] The present invention also relates to a process for making granulates from a powder mixture containing at least a filler or at least an active ingredient or both as components. For this, the powder mixture to be granulated may also contain a binder and / or a disintegrant, and optionally further conventional auxiliaries, and granulation is carried out with mixing by adding a granulation aid, which is potassium sodium tartrate tetrahydrate (PST), and increasing the temperature of the mixture to above 50°C, inducing syneresis of at least a portion of the crystallization water of PST to granulate the powder mixture. The preferred temperature of the powder mixture is increased to a temperature between 50°C and 120°C, more preferably to a temperature between 80°C and 110°C. Thermal heat for increasing the temperature is generated by a heating device.

[0016] Any form of heating device may be used in accordance with the present invention, with microwave radiation sources, infrared heaters, infrared dryers, high shear mixers, and extruders being preferred, and 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] Configuration of the high shear screws in a twin screw extruder used for granulation. [Diagram 2] 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 the produced granulates were determined using a Malvern Mastersizer 2000 (FAMalvern Panalytical). Granules in dry powder form were measured at a dispersion air pressure of 1.0-2.0 bar for approximately 30-60 seconds.

[0020] The crystal water content (water loss) of PST under the influence of heat was determined.

[0021] a) Infrared radiation 2 g of chemically pure PST were heated to 100° C. using the heating program of an infrared drying wedge (Sartorius MA 150). The temperature was kept constant until no further mass loss occurred. The mass loss allowed the dehydration of water of crystallization from the PST to be determined.

[0022] b) Ultrasonic To investigate the effect of ultrasound on the syneresis of the water of crystallization, 3 g of chemically pure PST was weighed into a penicillin vial and sonicated for 1 h in an ultrasonic bath. Outbound weighing allows the determination of the mass loss.

[0023] c) Microwave A microwave oven (Sharp RV10 (750 W; 2450 MHz) was used to test the effect of microwaves on PST. 2 g of chemically pure PST was weighed in a watch glass and placed in the microwave oven (power setting 30%) for 5 min. Flow-through weighing allows the determination of mass loss.

[0024] 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 or Figure 2.

[0025] [Table 1]

[0026] The granulate exiting the extruder was further processed directly by a milling process to give a good uniform particle size distribution, or more preferably by a sieving process, to obtain a granulate with a particle size particularly suitable for tableting (see Table 9).

[0027] Granulation using a single vessel batch mixer (Diosna P1-6) equipped with jacket heating To granulate the powder mixture, each component was weighed and placed directly into a 3 L bowl equipped with jacket heating option. Tests were performed at room temperature (RT) unless jacket heating was not required. Once the powder was placed into the granulator, granulation was started for the specified time range at the stated mill and impeller rotor rotation speeds. Finally, liquid was added during the process.

[0028] The resulting wet granulate was first sieved through a 2000 μm steel sieve and finally dried for 72 hours at room temperature and subsequently sieved through an 800 μm steel sieve.

[0029] The dry granules obtained by inducing syneresis and recombining water via various salts can be directly sieved through an 800 μm steel sieve.

[0030] [Table 2]

[0031] Tablet forming: The granulate preparation was sieved using a vibrating sieve shaker (Retsch-AS200) with mesh size within 125 μm to 1000 μm at an amplitude of 1.0 mm / g for approximately 2 minutes.

[0032] The sieved 125 μm-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.

[0033] Tableting was carried out on a multi-functional R&D press (Medelpharm-Styl'one Evo) equipped with biplane punches with different diameters. Compaction pressures varied from 50 MPa to 400 MPa.

[0034] Tablets were analyzed (10 tablets per test) using a semi-automatic tablet hardness tester (Sotax-SmartTest50). Tensile strength was measured according to USP <1217> In distilled water, it can be calculated according to USP <701> The disintegration was measured using a disintegration tester (Sotax-DT50) according to the method described above.

[0035] [Table 3]

[0036] [Table 4]

[0037] [Table 5]

[0038] [Table 6]

[0039] [Table 7]

[0040] [Table 8]

[0041] [Table 9]

[0042] [Table 10]

[0043]

Table 11

[0044]

Table 12

[0045]

Table 13

[0046]

Table 14

[0047]

Table 15

[0048]

Table 16

[0049]

Table 17

[0050]

Table 18

[0051]

Table 19

[0052]

Table 20

[0053]

Table 21

[0054]

Table 22

[0055]

Table 23

[0056]

Table 24

[0057]

Table 25

[0058]

Table 26

[0059]

Table 27

[0060]

Table 28

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 wt. % PST; d. 0-12.5% ​​by weight of at least one disintegrant; e. 0 to 98.5% by weight of at least one active ingredient; a powder mixture in which the total 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 wt. % PST; d. 0-12.5% ​​by weight of at least one disintegrant; e. 0 to 98.5% by weight of at least one active ingredient; f. 0 to 15 wt. % of further conventional auxiliaries; A powder mixture in which the total of the components a. to f. is 100% by weight.

2. A powder mixture for making a granulate, comprising: a. 7 to 97 wt. % of at least one filler; b. 1.5 to 10 wt. % of at least one binder; c. 1.5 to 25 wt. % PST; d. 0-10% by weight of at least one disintegrant; e. 0-90% by weight of at least one active ingredient; a powder mixture in which the total of the components a. to e. is 100% by weight; or A powder mixture for making a granulate, comprising: a. 7 to 97 wt. % of at least one filler; b. 1.5 to 10 wt. % of at least one binder; c. 1.5 to 25 wt. % PST; d. 0-10% by weight of at least one disintegrant; e. 0 to 98.5% by weight of at least one active ingredient; f. 0 to 10 wt. % of further conventional auxiliaries; A powder mixture in which the total of the components a. to f. is 100% by weight.

3. A powder mixture for making a granulate, comprising: a. 10 to 95 wt. % of at least one filler; b. 2.5 to 10 wt. % of at least one binder; c. 2.5 to 20 wt. % PST; d. 0-7.5 wt. % of at least one disintegrant; e. 0-85% by weight of at least one active ingredient; a powder mixture in which the total of the components a. to e. is 100% by weight; or A powder mixture for making a granulate, comprising: a. 10 to 95 wt. % of at least one filler; b. 2.5 to 15 wt. % of at least one binder; c. 2.5 to 20 wt. % PST; d. 0-7.5 wt. % 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 in which the total of the components a. to f. is 100% by weight.

4. 4. The powder mixture according to claim 1, wherein the PST particles have an average particle size d(0.5) of less than 300 μm.

5. 1. A process for making 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 conventional auxiliary, wherein granulation is carried out with mixing by adding a granulation auxiliary which is potassium sodium tartrate tetrahydrate (PST), raising the temperature of the mixture to 50°C or higher, and inducing syneresis of at least a portion of the water of crystallization of the PST to granulate the powder mixture.

6. 6. The process of claim 5, wherein the temperature of the powder mixture to be granulated is raised to 80-110°C.

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

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

10. 6. The process of claim 5, wherein the granulate produced is directly milled or sieved.

11. 6. The process of claim 5, wherein the granulate is produced continuously.

12. Granulate obtained by the process according to claim 5 for tableting or filling capsules.

13. Use of PST as a component in powder mixtures as a granulation aid.

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