WO2022078826A1

WO2022078826A1 - Nutraceutical or pharmaceutical composition

Info

Publication number: WO2022078826A1
Application number: PCT/EP2021/077499
Authority: WO
Inventors: Ashish Guha; Priyanka HAKSAR; Suresh DOKE; Nilam BHARAMBE; Shraddha Joshi
Original assignee: Evonik Operations Gmbh
Priority date: 2020-10-16
Filing date: 2021-10-06
Publication date: 2022-04-21

Abstract

The invention is concerned with a nutraceutical or pharmaceutical composition comprising a core, comprising a nutraceutically or pharmaceutically active ingredient, and a coating layer covering the core, wherein the coating layer is comprising a) a film-forming polymer, b) 1 to 100 % by weight, based on the weight of a), of a powder of comminuted outer coats of seeds of grain and optionally c) 0 to 80 % by weight, based on the weight of a), of a salt of alginic acid and/or a pectin, d) 0 to 50 % by weight, based on the weight of a), of a plasticizer, e) 0 to 200 % by weight, based on the weight of a), of further excipients, wherein a) and b) and optionally c), d) and/or e) add up to 100 %.

Description

Nutraceutical or pharmaceutical composition

Field of the invention

The invention is in the field of nutraceutical or pharmaceutical composition comprising a core, comprising a nutraceutically or pharmaceutically active ingredient, and a coating layer covering the core.

Technical Background

For nutraceutical or pharmaceutical composition comprising a core, comprising a nutraceutically or pharmaceutically active ingredient, and a coating layer covering the core, there is generally a permanent need for improving the coating composition in respect to their processability and release-specific properties. Especially there is a permanent need to reduce the spraying times. For coated immediate release compositions there is a need to ensure that the immediate release characteristics will not be impaired under storage conditions. For delayed release compositions there is a need to provide stable gastric resistance at low levels, below 10 % or even less active ingredient release at pH 1 .2 for 2 hours, without impairing the ability the set the active ingredient free at a desired level in higher pH environments for instance between pH 5.5 and 7.

Nutraceutical and pharmaceutical polymeric coating systems also underly growing health concerns. Naturally obtained ingredients which are not or only minimally treated chemically are of high interest due to their known advantageous contribution to human health. Thus, there is a need to avoid or to substitute ingredients or excipients which are not from natural origin, however without impairing the above-mentioned indispensable properties of the well-established compositions.

Especially properties such as the release characteristics in gastric or enteric environments, the processability, e.g. the spray rates or storage behavior, should be at least kept on the same high level as for conventional composition using chemically derived excipients.

There are also growing concerns in the dietary supplement/nutraceutical domain regarding safety issue associated with use of talc-containing coatings systems applied on such products. There is a strongly felt need to develop ‘talc-free’ coating systems for pharmaceutical and nutraceutical use.

US8492444B2 describes biogenic silica from silica-containing plant materials such as rice hulls. Disclosed is a human or animal food product containing no synthetic amorphous silica and comprising 2% by weight or less raw rice hulls containing from 15 to 23% by weight amorphous silica in the outer layers of the rice hulls. Said amount of said rice hulls is effective as an anti-caking agent, excipient or a flavor carrier at a usage level substantially the same as synthetic amorphous silica for the same function as an anti-caking agent, excipient or a flavor carrier. The teaching of US8492444B2 is based on the observation that rice hulls may be used as a biogenic source of amorphous silica as an anti-caking agent or flavor carrier in foods, drinks, supplements, personal care products and pharmaceuticals. US8492444B2 mentions that the usage level of rice husk to be the same as the usage level of synthetic amorphous silica. Grinding of the rice hulls may affect functionality. When the rice hulls are grounded in a ball mill, it is possible to achieve particle sizes in the range of 7 to 20 microns. Other mills may be able to reduce the particle size below 1 micron. However, larger quantities may be required to compensate for the lower concentration of silica as compared to fumed silica. The use of rice hulls in pharmaceutical or nutraceutical coatings to be applied on solid dosage forms like tablets, capsules or pellets is not disclosed or suggested in US8492444B2. Due to the particulate fibrous structure of rice hulls or rice husk, there can be serious doubts if the use of rice hulls would be suitable for pharmaceutical or nutraceutical coatings to substitute silica or talc without impairing the advantageous functions of those well-established excipients.

Commercially available products consisting of or comprising rice hulls or rice husk are known as Nu-FLOW™ or Nu-MAG™ (RIBUS Inc., USA). Nu-FLOW™ is made from rice hulls that are sterilized and ground to a fine powder. According to the manufacturer, Nu-FLOW™ shall offer producers an option to replace synthetics or other anti-caking agents like SiO2, tri-calcium phosphate or talc with a natural or certified organic ingredient. Nu-MAG™ is a blend of four ingredients (Rice Extract, Rice Hulls, Gum Arabic and Sunflower Oil) that shall help manufacturers to eliminate synthetic ingredients without compromising the quality or efficacy of their formulations. Nu-MAG™ shall offer formulators a certified organic alternative to magnesium stearate, so organic tablets requiring a lubricant could now be produced. Nu-MAG™ (stearate replacer) is announced as the clean label lubricant.

Summary of the invention

The invention provides healthy alternate compositions for coating of nutraceutical and pharmaceutical dosage forms like capsules and tablets, containing insoluble fibers derived from natural outer coatings of (food) grains, providing unique manufacturing advantages like high speed processing on commercial coating machines while avoiding health issues associated with ingredients such as talc. The invention avoids drawbacks of the coating functions of conventional compositions and even provides several advantageous and unexpected effects, e.g. improvements of properties, such as spraying ability (speed), storage stability and improved gastric resistance.

The objects are solved by a nutraceutical or pharmaceutical composition comprising a core, comprising a nutraceutically or pharmaceutically active ingredient, and a coating layer covering the core, wherein the coating layer is comprising a) a film-forming polymer, b) 1 to 100 % by weight, based on the weight of a), of a powder of comminuted outer coats of seeds of grain and optionally c) 0 to 80 % by weight, based on the weight of a), of a salt of alginic acid and/or a pectin d) 0 to 50 % by weight, based on the weight of a), of a plasticizer, e) 0 to 200 % by weight, based on the weight of a), of further excipients, wherein a) and b) and optionally c), d) and/or e) add up to 100 %.

Detailed description

It was surprisingly found that when commonly used coating polymers were combined with a powder of comminuted outer coats of seeds of (food) grain, the resultant coating systems had superior properties as compared to those with conventional excipients or without it. The coating process time was significantly reduced in presence of such powdered natural ingredients. It was also found that such powders having natural combined content by weight of hemicellulose and cellulose with respect to lignin in the range of 1 : 0.1 to 1 : 0.8 were most useful. Such powders, for instance obtained from rice husk or wheat bran, were of special significance. It was also found that it was possible to eliminate undesirable use of talc in such coating systems. It was possible to develop formulations with different release characteristics like delayed release and immediate release. It was also surprising to note that the delayed release formulations developed with inventive coating systems containing said powdered natural ingredient, had better acid resistance as compared to those not containing such ingredient.

As another surprising effect, coated products developed using above described inventive coating compositions had better stability profile as compared to those without it. Another advantage associated with the use of such innovative coating system was the ability to modulate flow behavior of coated particles in the blend, thereby helping in prevention of segregation of particles in blends and compressed dosage forms, important for ensuring better content uniformity of the components. The invention is concerned with a nutraceutical or pharmaceutical composition comprising a core, comprising a nutraceutically or pharmaceutically active ingredient, and a coating layer covering the core, wherein the coating layer is comprising a) a film-forming polymer, b) 1 to 100, preferably 20 to 80, most preferably 30 to 70 % by weight, based on the weight of a), of a powder of the outer coats of seeds of grain and optionally c) 0 to 80, preferably 30 to 70 % by weight, based on the weight of a), of a salt of alginic acid and/or a pectin, d) 0 to 50, preferably 2 to 40, most preferably 5 to 25 % by weight, based on the weight of a), of a plasticizer, e) 0 to 200, preferably 0.1 to 200 % by weight, based on the weight of a), of further excipients, wherein a) and b) and optionally c), d) and/or e) add up to 100 %.

The composition may be advantageously characterized in that the coating layer comprises comminuted outer coatings of seed grain, preferably from rice husk, but no essential amounts of talc or no talc at all, and in that the coating layer can be applied by spraying at a maximum sprayrate in g/min per kg core, which is higher by a factor of at least 1.1 , preferably by a factor of at least 1 .3, most preferably by a factor of at least 1 .8 compared to the same composition but comprising talc instead of comminuted outer coatings of seed grain, preferably from rice husk, in the same concentration.

Core

The core of the composition may be a crystal, a granule, a pellet, a tablet, a mini-tablet, a sprinkle or a capsule, comprising a nutraceutically or pharmaceutically active ingredient.

Nutraceutically or pharmaceutically active ingredient

The invention is preferably useful for immediate or delayed release formulated pharmaceutical or nutraceutical compositions or dosage forms.

Suitable therapeutic and chemical classes of pharmaceutically active ingredients which members may be used as fill-in for the described polymer-coated hard shell capsules are for instance: analgesics, antibiotics or anti-infectives, antibodies, antiepileptics, antigens from plants, antirheumatics, benzimidazole derivatives, beta-blocker, cardiovascular drugs, chemotherapeutics, CNS drugs, digitalis glycosides, gastrointestinal drugs, e.g. proton pump inhibitors, enzymes, hormones, liquid or solid natural extracts, oligonucleotides, peptide hormones proteins, therapeutic bacteria, peptides, protein (metal)salts, i.e. aspartates, chlorides, orthates, urology drugs and vaccines.

Further examples of drugs that may be used as fill-in for the described polymer-coated hard shell capsules are for instance acamprosat, aescin, amylase, acetylsalicylic acid, adrenalin, 5-amino salicylic acid, aureomycin, bacitracin, balsalazine, beta carotene, bicalutamid, bisacodyl, bromelain, budesonide, caffeine, calcitonin, carbamacipine, carboplatin, cephalosporins, cetrorelix, clarithromycin, Chloromycetin, cimetidine, cisapride, cladribine, clorazepate, cromalyn, 1- deaminocysteine-8-D-arginine-vasopressin, deramciclane, detirelix, dexlansoprazole, diclofenac, didanosine, digitoxin and other digitalis glycosides, dihydrostreptomycin, dimethicone, divalproex, drospirenone, duloxetine, enzymes, erythromycin, esomeprazole, estrogens, etoposide, famotidine, fluorides, garlic oil, glucagon, granulocyte colony stimulating factor (G-CSF), heparin, hydrocortisone, human growth hormon (hGH), ibuprofen, ilaprazole, insulin, Interferon, Interleukin, Intron A, ketoprofen, lansoprazole, leuprolidacetat lipase, lipoic acid, lithium, kinin, memantine, mesalazine, methenamine, metoprolol, milameline, minerals, minoprazole, naproxen, natamycin, nitrofurantion, novobiocin, olsalazine, omeprazole, orothates, pancreatin, pantoprazole, parathyroidhormone, paroxetine, penicillin, perprazol, pindolol, polymyxin, potassium, pravastatin, prednisone, preglumetacin progabide, pro-somatostatin, protease, quinapril, rabeprazole, ranitidine, ranolazine, reboxetine, rutosid, somatostatin streptomycin, subtilin, sulfasalazine, sulphanilamide, tamsulosin, tenatoprazole, thrypsine, valproic acid, vasopressin, vitamins, zinc, including their salts, derivatives, polymorphs, isomorphs, or any kinds of mixtures or combinations thereof.

It is evident to a skilled person that there is a broad overlap between the terms pharmaceutically and nutraceutically active ingredients, excipients and compositions respectively a pharmaceutical or a nutraceutical dosage form. Many substances listed as nutraceuticals may also be used as pharmaceutically active ingredients. Depending on the specific application and local authority legislation and classification, the same substance may be listed as a pharmaceutically or a nutraceutically active ingredient respectively a pharmaceutical or a nutraceutical composition or even both.

Nutraceuticals are well known to the skilled person. Nutraceuticals are often defined as extracts of foods claimed to have medical effects on human health. Thus, nutraceutically active ingredients may display pharmaceutical activities as well: Examples for nutraceutically active ingredients may be resveratrol from grape products as an antioxidant, soluble dietary fiber products, such as psyllium seed husk for reducing hypercholesterolemia, broccoli (sulphane) as a cancer preservative, and soy or clover (isoflavonoids) to improve arterial health. Thus, it becomes clear that many substances listed as nutraceuticals may also be used as pharmaceutically active ingredients.

Typical nutraceuticals or nutraceutically active ingredients that may be used for instance as fill-in for capsules may also include probiotics and prebiotics. Probiotics are living microorganisms believed to support human or animal health when consumed. Prebiotics are nutraceuticals or nutraceutically active ingredients that induce or promote the growth or activity of beneficial microorganisms in the human or animal intestine.

Examples for nutraceuticals are resveratrol from grape products, omega-3 or omega-6 fatty acids and their salts with amino acids (such as lysine, arginine, ornithine), choline, magnesium or potassium, ornithine-aspartate, anthocyanins or pro-anthocyanins from blueberries, bilberries or black currants as antioxidants, soluble dietary fiber products, such as psyllium seed husk for reducing hypercholesterolemia, broccoli (sulphane) as a cancer preservative, and soy or clover (isoflavonoids) to improve arterial health. Other nutraceuticals examples are flavonoids, antioxidants, alpha-linoleic acid from flax seed, beta-carotene from marigold petals or anthocyanins, from berries, and vitamins. Sometimes the expression neutraceuticals or nutriceuticals are used as synonyms for nutraceuticals.

Coating layer

A coating layer covering the core, wherein the coating layer is comprising a) a film-forming polymer, b) 1 to 100, preferably 20 to 80, most preferably 30 to 70 % by weight, based on the weight of a), of a powder of the outer coats of seeds of grain and optionally c) 0 to 80, preferably 30 to 70 % by weight, based on the weight of a), of a salt of alginic acid and/or a pectin, d) 0 to 50, preferably 2 to 40, most preferably 5 to 25 % by weight, based on the weight of a), of a plasticizer, e) 0 to 200, preferably 0.1 to 200 % by weight, based on the weight of a), of further excipients, wherein a) and b) and optionally c), d) and/or e) add up to 100 %.

The amount of the coating layer applied onto the core may be from about 1 to 30, preferably from about 1 .5 to 20, most preferably from about 2 to 10 mg/cm².

The coating layer may also comprise powders of comminuted outer coats of seeds of grain, preferably from rice husk, but no essential amounts of talc or no talc as further excipients e). Film-forming polymer (a)

The film-forming polymer a) may be selected from cellulose, polyvinyl alcohol (PVA), PVA-PEG graft copolymer, polylactide polymer (PLA), poly(lactide-co-glycolide (PLGA), copolymers of PLA, polyvinyl acetate, polyvinyl pyrrolidone (PVP, Povidone), polyurethans, polyorthoesters, shellac, a (meth)acrylate copolymer and a modified starch or any combinations thereof, preferably an acetylated starch.

The term cellulose shall be understood as all kinds of celluloses, including natural celluloses as well as chemically modified celluloses (derivates of cellulose), especially cellulose ethers like methyl, ethyl and propyl ethers of cellulose, such as hydroxypropylmethyl cellulose (HPMC).

The coating layer may comprise a modified starch, preferably an acetylated starch, most preferably an acetylated pre-gelled starch, with a d90 particle size of less than 150 pm, preferably 50 to 120 pm. The d90 particle size value may be determined by light or laser diffraction methods.

Modified starches, also called starch derivatives, may be prepared by physically, enzymatically, or chemically treating native starch. Starches are modified to enhance their properties. Starches may be modified to increase their stability against heat, acid, shear, cooling, freezing, or stability over time. Modification may also change their texture, decrease or increase their viscosity, lengthen or shorten gelatinization time or may increase their visco-stability.

Preferably, the modified starch is an acetylated starch, preferably an acetylated pre-gelled starch, and comprises maize starch.

Modification of starch by acetylation is well known and for instance described in EP1296658B1 . Starch, for instance maize starch, may be preferably acetylated with acetic anhydride, resulting in a content of acetylated groups of about 0.5 to 2.5 % by weight.

The acetylated starch may be pre-gelled by known methods. The acetylated starch may for instance be dispersed in an aqueous medium, water, and may then be poured onto a rotating drum at a temperature of about 100 to 130 °C, operating at pressures of 2 to 3 bar so that on touching the roll surface the dispersion “explodes” under evaporation of water in about 30 sec to 3 minutes. A gel layer comprising the starch is thus deposited on the surface of the rotating drum. The starch gel, with a humidity of about 5 to 10 % by weight, solidifies and may be scratched from the wall. The modified, acetylated and pre-gelled starch may be dried and milled to a powder in particulate form with a d90 particle size in the range of about 10 to 125 pm. Preferably, the modified starch is an acetylated starch, preferably an acetylated pre-gelled starch, and comprises a content of amylose of at least 50, preferably at least 90 % by weight and a content of acetylated groups of 0.5 to 2.5 % by weight.

The acetylated starch may be used is in particulate form with a d50 particle size in the range of 10 to 500, preferably 10 to 250 pm.

Preferably, an acetylated starch used is in particulate form with a d90 particle size in the range of about 10 to 125 pm.

Particle sizes, especially the particle sizes d10, d50 or d90, may be determined by light diffraction (laser scattering, s. United States Pharmacopeia 36 (USP) chapter <429> and European Pharmacopeia 7.0 (EP) chapter 2.9.31).

An acetylated pre-gelled starch product is known as acetylated Eurylon® G. Another suitable commercially available product is for instance EUDRAGUARD® Natural (Evonik Operations GmbH, Germany).

The composition may, as an immediate release composition, preferably comprise a modified, preferably an acetylated starch and/or a dimethylaminoethyl methacrylate copolymer as filmforming polymer a).

The dimethylaminoethyl methacrylate copolymer may be a copolymer comprising polymerized monomers of dimethylaminoethyl methacrylate, butyl methacrylate and methyl methacrylate, wherein the monomers add up to 100 %.

The dimethylaminoethyl methacrylate copolymer may be a copolymer comprising polymerized monomers of 40 to 60 % by weight of dimethylaminoethyl methacrylate, 20 to 30 % by weight of butyl methacrylate and 20 to 30 % by weight of methyl methacrylate, wherein the monomers add up to 100 %. The dimethylaminoethyl methacrylate copolymer may be a commercially available product such as EUDRAGIT® E, EUDRAGIT® E PO or EUDRAGUARD® protect (Evonik Operations GmbH, Germany).

Powders of comminuted outer coats of seeds of grain (b)

Powders of comminuted outer coats of seeds of grain, especially of food grain, are used as a source of silica that can replace conventional amorphous silica (SiO2) or talc (a mineral of layered silica with the chemical formula MgsSi+OwCOH)) as anti-caking or processing agents of natural source in nutraceutical or pharmaceutical compositions or applications. Rice hulls (or rice husks), for example, are the hard, protecting coverings (coats) of seeds of grain from rice. Rice husk or rice hulls may contain about 15 - 23 % by weight of (amorphous) silica. Grain may be defined as the seeds of plants, especially cereal (food) plants, preferably such as wheat, corn, rye, oats, rice or millet. Food grain is preferred. Food grain is grain that may be or is used as a source for human or animal food.

The composition as disclosed may for instance comprise 1 to 100, preferably 20 to 80, most preferably 30 to 70 % by weight, based on the weight of the film-forming polymer a), of a powder of comminuted outer coats of seeds of grain, preferably from the seeds of wheat, corn, rye, oats, rice or millet.

The composition may be characterized, wherein the powder of comminuted outer coats of seeds of grain comprises at least 5, preferably at least 15 % by weight of (amorphous) silica (SiC>2). The silica content can be determined by a skilled person by well-known analytical methods.

The composition may be characterized, wherein the powder of comminuted outer coats of seeds of grains comprise a ratio of hemicellulose and cellulose to lignin in the range of 1 : 0.1 to 1 : 0.8 by weight. The content of hemicellulose and cellulose to lignin may be analyzed by well-known analytical methods.

The powder of comminuted outer coats of seeds of grain preferably comprises comminuted outer coats of seeds of grain from wheat (Triticum spec., wheat bran), pearl millet (Pennisetum glaucum), finger millet (Eleusine coracana), jowar (Sorghum bicolor), foxtail millet (Setaria italica or synonymous Panicum italicum) , Kodo Millet (Paspalum scrobiculatum), little millet (Panicum sumatrense), barnyard millet (Echinochloa esculenta), preferably from rice, e.g. rice husk (Oryza spec.). The powder of comminuted outer coats of seeds of grain may contain particles with a particle size d50 in the range of about 10 to 100, preferably 25 to 80 pm. Suitable particles in that size range may be provided after grinding by sieving. The particle size d50 may be determined by well-known methods such as light detraction.

The powder of comminuted outer coats of seeds of grain may contain rice husk particles with a particle size d50 in the range of about 10 to 100, preferably 25 to 80 pm.

Preferably, a powder of comminuted rice husk may contain rice husk particles with particle size d50 in the range of about 10 to 100, preferably 25 to 80 pm (determined by sieving method or particle size analyzer). Particle sizes, especially the particle sizes d10, d50 or d90, may be determined by light diffraction (laser scattering, s. United States Pharmacopeia 36 (USP) chapter <429> and European Pharmacopeia 7.0 (EP) chapter 2.9.31) or by image analysis. Commercially available products consisting of or comprising rice hulls or rice husk are known as Nu-FLOW™ orNu-MAG™ (RIBUS Inc., USA). Nu-FLOW™ is made from rice hulls that are sterilized and ground to a fine powder.

Particle size determination

The raw plant material respectively the outer coats of seeds of grain may be comminuted by grinding or milling to a suitable particle size. Particle fractions may be obtained by sieving. The average particle size d50 may be determined by a particle size analyzer.

Light diffraction

The determination of the particle size may be performed according to the United States Pharmacopeia 36 (USP) chapter <429> and European Pharmacopeia 7.0 (EP) chapter 2.9.31. The particle size distribution was determined utilizing a laser scattering instrument (e.g. Fa. Sympatec GmbH, type HELOS equipped with RODOS dry dispersing unit). The laser diffraction method is based on the phenomenon that particles scatter light in all directions with an intensity pattern that is dependent on particle size. A representative sample, dispersed at an adequate concentration in a suitable liquid or gas, is passed through the beam of a monochromic light source usually from a laser. The light scattered by the particles at various angles is measured by a multi-element detector, and numerical values relating to the scattering pattern are then recorded for subsequent analysis. The numerical scattering values are then transformed, using an appropriate optical model and mathematical procedure, to yield the proportion of total volume to a discrete number of size classes forming a volumetric particle size distribution (e.g. d50 describes a particle diameter corresponding to 50% of cumulative undersize distribution).

Particle size distribution I Image analysis

Alternatively to the laser diffraction method, a dynamic image analysis may be used after qualification with referencing to the light diffraction method. The basic concept is the combination of dry dispersing unit with dynamic image analysis (Fa. Sympatec GmbH, type QICPIC equipped with RODOS/L dry dispersing unit). A representative sample is dry dispersed, and the particle flow is led through the image plane. Due to the dispersion the particles are separated from each other by the transportation fluid and overlapping particles are widely avoided. Dry samples are transferred into aerosols by use of powder dispersers, which apply mechanical forces for deagglomeration. The dosing device feeds the disperser with a constant mass flow of sample. The disperser utilizes the energy of compressed gas (e.g. 1 bar) or the differential pressure to a vacuum (e.g. 90 - 100 mbar) to disperse the particles. The required precision of the method is dependent on characteristics of the sample material (milled versus non-milled, robust vs. fragile). Appropriate measurement conditions are experimentally established, in relation to the desired precision. At least a triplicate detection of representative samples was conducted. The repeatability of the particle size distribution parameter was as follows: for any central value of the distribution (e.g. median d50) the coefficient of variation was less than 10 %. For values away from the median, (e.g. d10 and d90) the coefficient of variation does not exceed 15 %. Below a particle size of 10 pm the coefficient of variation may be doubled.

Salt of alginic acid and/or a pectin (c)

The composition may optionally comprise a salt of alginic acid and/or a pectin. The addition of a salt of alginic acid and/or a pectin is usually recommendable in the delayed release compositions. For the immediate release compositions, a salt of alginic acid and/or a pectin may be omitted.

The composition may optionally comprise 0 to 80, preferably 30 to 70 % by weight, based on the weight of the film-forming polymer a), of a salt of alginic acid and/or a pectin.

Pectin is a plant-derived natural product found in the middle lamellas between plant cells but also in primary plant cell walls. Pectin is a polysaccharide with galacturonic acid as main monomer component. Pectin is also widely used a gelling agent in foods, medicines and nutraceuticals.

Commonly used pectins are derived from apple or citrus fruits.

Preferred, a salt of alginic acid is employed. The salt of alginic acid may be an alkali or an ammonium salt of alginic acid or any mixture thereof. Preferably, the salt of alginic acid may be selected from sodium alginate, potassium alginate and ammonium alginate or any mixtures thereof.

The salt of alginic acid may have a viscosity of 30 to 720 cP in a 1 % aqueous solution (weight /weight) at 25 °C.

Viscosity

The salts of alginic acid employed may have a viscosity of 30 to 720, preferably 40 to 450, preferably 40 to 400 or preferably 50 to 300 centipoise (cP) of a 1 % aqueous solution (weight /weight). Unit: 1 cP = 1 mPa s.

The methodology of determination of the viscosity of a polymer solution, for instance a solution of a salt of alginic acid, is well known to the skilled person. The viscosity is preferably determined according to European Pharmacopeia 7th edition, general chapter 2, methods of analysis, 2.2.8 and 2.2.10, page 27ff. The test is performed using a spindle viscometer.

The viscosity of a 1 % alginate solution (weight /weight) may be determined by adding 3 g product to 250 ml of distilled water in a beaker while stirring at 800 rpm using an overhead stirrer. Then, additional 47 ml water are added with rinsing the walls of the beaker. After stirring for 2 hours and getting a complete solution, the viscosity is measured using a LV model of the Brookfield viscometer at 25 °C (77 °F) at 60 rpm with no. 2 spindle for samples with a viscosity of more than 100 cP and at 60 rpm with no. 1 spindle for samples with viscosity less than 100 cP. Since the weight of water is almost exactly 1g/ml, even at 25 °C “weight/weight” is regarded as equal or identical to “weight/volume” in the sense of the invention. Theoretically possible marginal differences are regarded as insignificant.

Plasticizer (d)

The composition may optionally comprise a plasticizer. Plasticizers may be defined in that they achieve through physical interaction with a polymer a reduction in the glass transition temperature and promote film formation, depending on the added amount. Suitable substances usually have a molecular weight of between 100 and 20,000 and comprise one or more hydrophilic groups in the molecule, e.g. hydroxy ester or amino groups.

The composition as disclosed may comprise 0 to 50, preferably 2 to 40, most preferably 5 to 25 % by weight, based on the weight of the film-forming polymer a), of a plasticizer.

The plasticizer may be selected from the groups of alkyl citrates, glycerol, glycerol esters, alkyl phthalates, alkyl sebacates, sugar alcohols, polyols, sucrose esters, sorbitan esters and polyethylene glycols or any mixtures thereof.

The plasticizer may be selected from triethyl citrate (TEC), acetyl triethyl citrate (ATEC), diethyl sebacate and dibutyl sebacate (DBS), glycerol, mannitol, xylitol, propylene glycol, polyethylene glycols 200 to 12,000, sunflower oil and castor oil or any mixtures thereof. Most preferred are glycerol and/or mannitol.

Further excipients (e)

The composition may optionally comprise further excipients. The composition may comprise 0 to 200, preferably 0.1 to 200 % by weight, based on the weight of the film-forming polymer a), of further excipients. Further excipients shall mean excipients which are not or do not overlap with the substances of the components a), b) c) or d) as disclosed. The further excipients shall be of course suitable to be used in nutraceutical or pharmaceutical applications.

The further excipients may be selected for instance from antioxidants, brighteners, binding agents, flavoring agents, flow aids, fragrances, glidants, penetration-promoting agents, pigments, polymers, pore-forming agents or stabilizers.

The further excipients may comprise for instance stearic acid or tartaric acid or both.

The further excipients may comprise rice extract, gum arabic and sunflower oil as included in Nu- MAG® (RIBUS Inc., USA), which is a commercially available rice husk powder product that comprises rice extract, gum arabic and sunflower oil as further excipients. The further excipients may also comprise phosphates, oils and waxes.

Preferably, the composition comprises no essential amounts of talc, preferably less than 10, preferably less than 2 and most preferably less than 1 % by weight, based on the weight of the filmforming polymer a), or no talc at all.

Immediate release composition

The composition may be an immediate release composition.

The composition may be an immediate release composition with an initial disintegration time in water of 30 min or less at 37 °C.

The determination of the disintegration time is well-known to a skilled person and may be determined according to European Pharmacopeia 5.0, 2.9.1.

Preferably, after three months of storage at 40 °C/75 % relative humidity, the disintegration time in water at 37 °C, compared to the initial disintegration time in water at 37 °C without storage, is increased by no more than 20 %, preferably no more than 15 %.

The coating may be applied by spraying at a maximum spray-rate in g/min per kg core, which is higher by a factor of at least 1.1 , preferably by a factor of at least 1 .2, most preferably by a factor of at least 1 .8 compared to the same composition but without the same powder of outer coats of seeds or grain, preferably powder of rice husk.

The composition may, as an immediate release composition, preferably comprise an acetylated starch and/or a dimethylaminoethyl methacrylate copolymer as film-forming polymer a). Acetylated starch products are well known, for instance from EP1296658B1 , and commercially available. EUDRAGUARD® natural (Evonik Operations GmbH, Germany) is a maize starch-based polymer, comprising acetylated starch.

The dimethylaminoethyl methacrylate copolymer may be a copolymer comprising polymerized monomers of 40 to 60 % by weight of dimethylaminoethyl methacrylate, 20 to 30 % by weight of butyl methacrylate and 20 to 30 % by weight of methyl methacrylate, wherein the monomers add up to 100 %. The dimethylaminoethyl methacrylate copolymer may be a commercially available product such as EUDRAGIT® E, EUDRAGIT® E PO or EUDRAGUARD® Protect (Evonik Operations GmbH, Germany). The immediate release composition may be advantageously characterized in that the coating layer can be applied by spraying at a maximum spray-rate in g/min per kg core, which is higher by a factor of at least 1.1 , preferably by a factor of at least 2, most preferably by a factor of at least 4 compared to the same composition but without powder of outer coats of seeds or grain, e.g. powder from rice husk.

Delayed release composition

The composition may be a delayed release composition.

The composition may be a delayed release composition comprising an acetylated starch in combination with a salt of alginic acid and/or a pectin.

Acetylated starch products are well known, for instance from EP1296658B1 , and commercially available. EUDRAGUARD® natural (Evonik Operations GmbH, Germany) is a maize starch-based polymer, comprising acetylated starch.

The release of the nutraceutically or pharmaceutically active ingredient after 2 hours in 0.1 N HCI pH 1 .2 medium according to USP (USP41 , paddle, method B, 50 rpm) may be about 10 % or less, preferably about 8 % or less.

The release of the nutraceutically or pharmaceutically active ingredient after 2 hours in 0.1 N HCI pH 1 .2 medium according to USP (USP41 , paddle, method B, 50 rpm) and subsequent for 180 min in buffered medium of pH 6.8 according to USP (USP 41) may be about 50 to 100, preferably 60 to 95 %.

The coating layer may also comprise comminuted outer coats of seeds of grain, preferably rice husk, but no essential amounts of talc or no talc as further excipients e).

The delayed release composition may be advantageously characterized in that wherein the coating layer comprises comminuted outer coatings of seed grain, preferably from rice husk, but no essential amounts of talc or no talc, and the coating layer can be applied by spraying at a maximum spray-rate in g/min per kg core, which is higher by a factor of at least 1 .1 , preferably by a factor of at least 1 .3, most preferably by a factor of at least 1 .8 compared to the same composition but comprising talc instead of comminuted outer coatings of seed grain, preferably from rice husk, in the same concentration. Process for preparing a nutraceutical or pharmaceutical composition

Disclosed is a process for preparing a nutraceutical or pharmaceutical composition according to any of the proceeding items by mixing and dispersing the components as disclosed in an aqueous solution, preferably with a water content of about 5 to 25, more preferably 10 to 20 % by weight, and spraying the dispersion onto the cores, for instance by using a fluidized bed spraying equipment.

Use

Disclosed is a powder of the outer coats of seeds or grain, preferably powder from rice husk, for use as (method of use) excipient in the coating layer of the nutraceutical or pharmaceutical composition as disclosed for increasing the spray-rate, in g/min per kg cores, of the coating dispersion when applying the coating onto the cores.

Preferably, the spray-rate, in g/min per kg cores, may be increased by a factor of at least 1.1 , preferably by a factor of at least 1 .3, most preferably by a factor of at least 1 .8 compared to a composition without powder of the outer coats of seeds of grain, respectively without powder from rice husk.

Items

The invention may be especially characterized by the following preferred embodiments:

The present invention is directed to a utraceutical or pharmaceutical composition comprising a core, comprising a nutraceutically or pharmaceutically active ingredient, and a coating layer covering the core, wherein the coating layer is comprising a) a film-forming polymer, b) 1 to 100, preferably 20 to 80, most preferably 30 to 70 % by weight, based on the weight of a), of a powder of the outer coats of seeds of grain and optionally c) 0 to 80, preferably 30 to 70 % by weight, based on the weight of a), of a salt of alginic acid and/or a pectin, d) 0 to 50, preferably 2 to 40, most preferably 5 to 25 % by weight, based on the weight of a), of a plasticizer, e) 0 to 200, preferably 0.1 to 200 % by weight, based on the weight of a), of further excipients, wherein a) and b) and optionally c), d) and/or e) add up to 100 %.

In a preferred configuration, the powder of the outer coats of seeds of grain comprises at least 5 % by weight of silica.

In a preferred configuration, the grain comprises wheat, corn, rye, oats, rice or millet.

In a preferred configuration, the powder of comminuted outer coats of seeds of grain comprises comminuted outer coats of seeds of grain from wheat (Triticum spec., wheat bran), pearl millet (Pennisetum glaucum), finger millet (Eleusine coracana), jowar (Sorghum bicolor), foxtail millet (Setaria italica or synonymous Panicum italicum) , Kodo Millet (Paspalum scrobiculatum), little millet (Panicum sumatrense) and/or barnyard millet (Echinochloa esculenta), preferably from rice, e.g. rice husk (Oryza spec.).

In a preferred configuration, the core is a crystal, a granule, a pellet, a tablet, a mini-tablet, a sprinkle or a capsule.

In a preferred configuration, the film-forming polymer is a cellulose, polyvinyl alcohol (PVA), PVA- PEG graft copolymer, PLA, PLGA, copolymer of PLA, polyvinyl acetate, polyvinyl pyrrolidone (PVP, Povidone), shellac or a (meth)acrylate copolymer, a modified starch or any combinations thereof, preferably an acetylated starch.

In a preferred configuration, the film-forming polymer is an acetylated starch, preferably an acetylated pre-gelled starch, and comprises maize starch. In a preferred configuration, the film-forming polymer is an acetylated starch and comprises a content of amylose of at least 50 % by weight and a content of acetylated groups of 0.5 to 2.5 % by weight.

In a preferred configuration, the acetylated starch used is in particulate form with a particle size d50 in the range of 10 to 500 pm.

In a preferred configuration, the powder of comminuted seeds from rice husk contains rice husk particles with a particle size d50 in the range of about 10 to 100 pm (determined by sieving method or particle size analyzer)

In a preferred configuration, the salt of alginic acid is an alkali or an ammonium salt of alginic acid or a mixture thereof.

In a preferred configuration, the salt of alginic acid is sodium alginate, potassium alginate or ammonium alginate or any mixtures thereof.

In a preferred configuration, the salt of alginic acid has a viscosity of 30 to 720 cP of a 1 % aqueous solution.

In a preferred configuration, the plasticizer is selected from the groups of alkyl citrates, glycerol, glycerol esters, alkyl phthalates, alkyl sebacates, sugar alcohols, sucrose esters, sorbitan esters and polyethylene glycols or any mixtures thereof.

In a preferred configuration, the plasticizer is selected from triethyl citrate (TEC), acetyl triethyl citrate (ATEC), diethyl sebacate and dibutyl sebacate (DBS), glycerol, mannitol, propylene glycol, polyethylene glycols 200 to 12,000, sunflower oil and castor oil or any mixtures thereof.

In a preferred configuration, the further excipients are selected from antioxidants, brighteners, binding agents, flavoring agents, flow aids, fragrances, glidants, penetration-promoting agents, pigments, polymers, pore-forming agents or stabilizers.

In a preferred configuration, the further excipients comprise stearic acid or tartaric acid or both.

In a preferred configuration, the further excipients comprise rice extract, gum arabic and sunflower oil.

In a preferred configuration, the further excipients comprise phosphates, oils and waxes.

In a preferred configuration, the amount of the coating layer applied onto the core is from about 1 to

30, preferably from about 1 .5 to 20, most preferably from about 2 to 10 mg/cm². In a preferred configuration, the composition comprises no essential amounts of talc, preferably less than 10, preferably less than 2 and most preferably less than 1 % by weight, based on the weight of a), or no talc at all.

In a preferred configuration, the composition is an immediate release composition.

In a preferred configuration, the composition is an immediate release composition with an initial disintegration time in water of 30 min or less at 37 °C.

In a preferred configuration, after three months of storage at 40 °C/75 % relative humidity the disintegration time in water at 37 °C compared to the initial disintegration time without storage is increased by no more than 20 %.

In a preferred configuration, the coating can be applied by spraying at a maximum spray-rate in g/min per kg core, which is higher by a factor of at least 1.1 , preferably by a factor of at least 1 .2, most preferably by a factor of at least 1 .8 compared to the same composition but without powder of comminuted rice husk.

In a preferred configuration, the composition comprises an acetylated starch and/or a dimethylaminoethyl methacrylate copolymer.

In a preferred configuration, the dimethylaminoethyl methacrylate copolymer is a copolymer comprising polymerized monomers of dimethylaminoethyl methacrylate, butyl methacrylate and methyl methacrylate, wherein the monomers add up to 100 %.

In a preferred configuration, the composition is a delayed release composition comprising an acetylated starch in combination with a salt of alginic acid and/or a pectin.

In a preferred configuration, the release of the nutraceutically or pharmaceutically active ingredient after 2 hours in 0.1 N HCI pH 1.2 medium according to USP (USP41 , paddle, method B, 50 rpm) is 10 % or less, preferably 8 % or less.

In a preferred configuration, the release of the nutraceutically or pharmaceutically active ingredient after 2 hours in 0.1 N HCI pH 1.2 medium according to USP (USP41 , paddle, method B, 50 rpm) and subsequent 180 min in buffered medium of pH 6.8 according to USP (USP 41) is 50 to 100 %.

In a preferred configuration, the coating layer comprises comminuted outer coatings of seed grain, preferably from rice husk, but no essential amounts of talc or no talc, and the coating layer can be applied by spraying at a maximum spray-rate in g/min per kg core, which is higher by a factor of at least 1 .1 , preferably by a factor of at least 1 .3, most preferably by a factor of at least 1 .8 compared to the same composition but comprising talc instead of comminuted outer coatings of seed grain, preferably from rice husk, in the same concentration. The present invention is also related to a process for preparing a nutraceutical or pharmaceutical composition according to the present invention by mixing and dispersing the components in an aqueous solution and spraying the dispersion onto the cores.

Moreover, the present invention is directed to a powder of the outer coats of seeds or grain, preferably powder from rice husk, for use as excipient in the coating layer of the nutraceutical or pharmaceutical composition according to the present invention for increasing the spray-rate, in g/min per kg cores, of the coating dispersion when applying the coating onto the cores.

In a preferred configuration, the spray-rate, in g/min per kg cores, is increased by a factor of at least 1 .1 , preferably by a factor of at least 1 .3, most preferably by a factor of at least 1 .8 compared to a composition without powder of the outer coats of seeds of grain, respectively without powder from rice husk.

Examples

I. Preparation of core tablets used for all the immediate release coating trials

(1) Composition of core tablets

Table 1 : Core tablet formula for immediate release coating.

(2) Process for preparation of core tablets

I. Caffeine was mixed in a blender for about 15 minutes with Mannitol, PVPK-25 and Aerosil® 200 after sifting thru # 25 ASTM sieve.

II. Magnesium stearate was sifted thru #40 ASTM sieve and added to the blend of step-l. Blended for another 3 minutes.

III. The blend of step-ll was compressed into tablets using D tooling fitted on a rotary compression machine.

IV. These compressed tablets were used for all the immediate release coating trials.

Table 2: Tablet compression parameters

II. Coating experiments conducted without and with the ingredients containing rice husk powder in immediate release coating systems

(1) Formula for coating of tablets Table 3: Coating formula containing comparative (C) and inventive (I) examples

* EUDRAGUARD natural milled to get the particle size: d₉₀ < 100pm

EUDRAGUARD natural (unprocessed) particle size: d₉₀ 350pm

** Quantity sufficient to make the volume.

(2) Preparation of coating dispersions of experiments C1 to I6 Preparation of coating solution for tablets coating: C1 , 11 , 12, 13

I. Mannitol was dissolved in the purified water under stirring.

II. EUDRAGUARD® natural (acetylated starch) was added to the solution of step-l under stirring. Continued stirring for about 30 minutes.

III.NUFLOW® or NUMAG® (as & if applicable) was added to the dispersion of step-ll under stirring. Continued stirring for another 15 minutes.

IV.The coating dispersion was passed through 40 # ASTM sieve (425 pm) and used for coating of tablets as described in the next section. Preparation of coating solution for tablets coating: C2, 14

I. Glycerol was dissolved in the hot purified water (~ 80°C) under stirring.

II. EUDRAGUARD® natural was added to the solution of step-1 under stirring. Continued stirring for about 30 minutes.

III. NUFLOW® was added (only in experiment - 14) to the dispersion of step-ll under stirring. Continued stirring for another 15 minutes

IV. The coating dispersion was passed through 40 # ASTM sieve (425 pm) and used for coating of tablets as described in the next section.

Preparation of coating solution for tablets coating: C3, 15, 16

I. Tartaric acid was dissolved in the purified water under stirring.

II. EUDRAGUARD® protect and stearic acid were added to the solution of step-l under stirring. Continued stirring for about 30 minutes.

III. NUMAG® or NUFLOW® was added (only in experiment - 15 & I6) to the dispersion of step-ll under stirring. Continued stirring for another 15 minutes.

(3) Coating of tablets

Compressed Caffeine tablets were coated with coating dispersions described in previous section using a drum coater with following parameters.

Table 4: Batch parameters for comparative and inventive examples C1 to I6

(4) Evaluation of coated tablets

Coated tablets were evaluated for surface appearance and disintegration time initially and after 3 months of storage at 40 °C / 75% RH.

Table 5: Evaluation of coated tablet containing comparative and inventive examples

III. Preparation of core tablets used for all the delayed release coating trials

(1) Composition of core tablets used for delayed release coating trials

Table 6: Core tablet formula for delayed release coating

(2) Process for preparation of core tablets

I. Caffeine was mixed in a blender for about 15 minutes with Microcrystalline cellulose, PVPK- 30, Talc, sodium starch glycolate and Aerosil® 200 after sifting thru # 25 ASTM sieve.

IV. Compressed tablets were used for all the delayed release coating trials Table 7: Tablet compression parameters

IV. Coating experiments conducted without and with the ingredients containing rice husk powder in delayed release coating systems

(3) Formula for coating of Tablets

Table 8: Coating formulations of comparative and inventive examples

* EUDRAGUARD® natural (unprocessed) particle size: d₉₀ <350 pm ** quantity sufficient to make 10% w/w solids dispersion

(4) Preparation of coating dispersions of experiments C4, C5 and I7 to 110

Preparation of coating solution for tablets coating: C4, C5 and I7 to 110

I. Glycerol was dissolved in the purified water under stirring.

II. EUDRAGUARD® natural was added to the solution of step-l under stirring. Continued stirring for about 30 minutes.

III. Sodium alginate was added to the step -II under stirring. Continued stirring for 30minutes.

IV.Talc, NUFLOW® or NUMAG® (as & if applicable) was added to the dispersion of step— III under stirring. Continued stirring for another 15 minutes. V. The coating dispersion was passed through 40 # ASTM sieve (425 pm) and used for coating of tablets as described in the next section.

(5) Coating of tablets Compressed Caffeine tablets were coated with coating dispersions described in previous section using a drum coater with following parameters.

Table 8: Batch parameters for comparative and inventive examples C4, C5 and 17 to 110

(6) Evaluation of coated tablets

Coated tablets were evaluated for surface appearance and dissolution.

Table 9: Evaluation of coated tablet containing comparative and inventive examples

V. Comparison of formulation disclosed in EP1157690A1with the current invention for the coating of caffeine tablets with EUDRAGIT® L30D-55

Caffeine tablets were prepared and coated with EUDRAGIT® L30D-55 as disclosed in EP1157690A1 as comparative examples (see T rails- 1 to IV in Table 10).

It was observed that the dispersion containing silica and EUDRAGIT L 30D-55 turned into a very viscous and thus non-sprayable form, even after dilution with additional water. This change in property of the dispersion was evident within 60 minutes of spray dispersion preparation. Range of silica concentration evaluated was 10 to 40% with respect to the dry polymer weight (as disclosed in EP1157690A1). Within this range, the dispersions with higher concentration of silica, presented more challenges on agglomeration and processability front as compared to the dispersion with least amount of silica in it. In an attempt to improve workability of the disclosed work, two different silica grades were tried; fumed silica (Aerosil 200) and precipitated silica (Syloid 244FP). All the trials are presented in table-10.

Although lower concentrations of silica 12.5% wrt polymer were stable for limited time period (up to 1 hr.), this is not suitable for industrial applications, where higher time ranges for stability are required. As a conclusion, rice husk powder and silica can not be used interchangeably in inventive coating formulations. Surprisingly the inventive coating dispersions containing rice husk were sufficiently stable, which are sprayable.

VI. Comparison of inventive example containing rice husk to silica for the coating of caffeine tablets with EUDRAGUARD® natural (modified starch) Caffeine tablets were prepared and coated with EUDRAGUARD® natural as comparative examples (see Trails-I to IV in Table 11).

Trial-I dispersion with fumed silica (Aerosil 200) could not be processed on coating machine due to sprayability, sticking and other process issues while trial -IV containing rice husk powder ran very well. Trial-ll and trial-ill were also conducted to ascertain effect of cellulose and its coexistence with silica respectively. Although the process performance of trial-ill was slightly better as compared to Trials I and II, it was still worse than comparative example C1 (example without any glidant). The surprising effect of rice husk based inventive dispersion (trial-IV) was unmatched in all cases. Trial- IV (I2) could be run without any process issues at an acceptable spray rate.

Claims

1 . Nutraceutical or pharmaceutical composition comprising a core, comprising a nutraceutically or pharmaceutically active ingredient, and a coating layer covering the core, wherein the coating layer is comprising a) a film-forming polymer, b) 1 to 100 % by weight, based on the weight of a), of a powder of comminuted outer coats of seeds of grain and optionally c) 0 to 80 % by weight, based on the weight of a), of a salt of alginic acid and/or a pectin d) 0 to 50 % by weight, based on the weight of a), of a plasticizer, e) 0 to 200 % by weight, based on the weight of a), of further excipients, wherein a) and b) and optionally c), d) and/or e) add up to 100 %.

2. Composition according to Claim 1 , wherein the powder of comminuted outer coats of seeds of grain comprises comminuted outer coats of grain from pearl millet, finger millet, jowar, foxtail millet, kodo millet, little millet, barnyard millet, wheat or wheat bran, preferably from rice (rice husk).

3. Composition to Claim 1 or 2, wherein the film-forming polymer is a cellulose, polyvinyl alcohol (PVA), PVA-PEG graft copolymer, PLA, PLGA, copolymers of PLA, polyvinyl acetate, polyvinyl pyrrolidone (PVP, Povidone), polyurethans, polyorthoesters, shellac or a (meth)acrylate copolymer, a modified starch or any combinations thereof, preferably an acetylated starch.

4. Composition according to any of the preceding Claims, wherein the film-forming polymer is an acetylated starch and comprises maize starch.

5. Composition according to any of the preceding Claims, wherein the film-forming polymer is an acetylated starch and comprises a content of amylose of at least 50 % by weight and a content of acetylated groups of 0.5 to 2.5 % by weight.

6. Composition according to any of the preceding Claims, wherein the salt of alginic acid is an alkali or an ammonium salt of alginic acid or a mixture thereof.

7. Composition according to any of the preceding Claims, wherein the plasticizer is selected from the groups of alkyl citrates, glycerol, glycerol esters, alkyl phthalates, alkyl sebacates, sugar alcohols, sucrose esters, sorbitan esters and polyethylene glycols or any mixtures thereof.

8. Composition according to any of the preceding Claims, wherein the further excipients are selected from antioxidants, brighteners, binding agents, flavoring agents, flow aids, fragrances, glidants, penetration-promoting agents, pigments, polymers, pore-forming agents or stabilizers.

9. Composition according to any of the preceding Claims, wherein the composition comprises no essential amounts of talc, preferably less than 10, preferably less than 2 and most preferably less than 1 % by weight, based on the weight of a), or no talc at all.

10. Composition according to any of the preceding Claims, wherein the composition is an immediate release composition.

11 . Composition according to any of the preceding Claims, wherein the composition is an immediate release composition with an initial disintegration time in water of 30 min or less at 37 °C.

12. Composition according to Claims 10 or 11 , wherein the composition comprises an acetylated starch and/or a dimethylaminoethyl methacrylate copolymer.

13. Composition according to any of Claims 1 to 9, wherein the composition is a delayed release composition comprising an acetylated starch in combination with a salt of alginic acid.

14. Process for preparing a nutraceutical or pharmaceutical composition according to any of the proceeding Claims by mixing and dispersing the components in an aqueous solution and spraying the dispersion onto the cores.

15. Powder of comminuted rice husks for use as excipient in the coating layer of the nutraceutical or pharmaceutical composition according to any of Claims 1 to 14 for increasing the maximum spray-rate, in g/min per kg cores, of the rice husk comprising coating dispersion when applying the coating onto the cores.