WO2022112959A1

WO2022112959A1 - Non-colouring turmeric formulation and a process for preparation thereof

Info

Publication number: WO2022112959A1
Application number: PCT/IB2021/060910
Authority: WO
Inventors: Vishal Shah; Rajat Shah; Sanjay Singh
Original assignee: Inventia Healthcare Limited
Priority date: 2020-11-25
Filing date: 2021-11-24
Publication date: 2022-06-02

Abstract

The present invention relates to a non-colouring turmeric formulation comprised of a blend of turmeric powder and curcumin extract, combined with at least about 10 to 25% by weight of a non-polymeric encapsulating agent and at least one excipient. The formulation may be comprised of blend of turmeric powder and curcumin extract, combined in various ratios ranging from 50:1 to 5:1. The invention also relates to the process for preparation of non-colouring formulation, wherein turmeric powder or its blend with curcumin extract may be granulated using at least one excipient and the granules are encapsulated using non-polymeric agent. The process for preparation is simple, cost effective and environment friendly. The non-colouring formulation is granular, free flowing and retains characteristic colour of the active; but does not cause any dusting and coloration of the area, contact surfaces and the equipment, while converting into various dosage forms.

Description

Non-colouring turmeric formulation and a process for preparation thereof Field of The Invention

The present invention relates to a non-colouring turmeric formulation and a process for the preparation thereof. The formulation may be specifically comprised of turmeric powder or a blend of turmeric powder and curcumin extract, combined in various ratios ranging from 50:1 to 5:1. The turmeric formulation may further be comprised of about 10% to 25% by weight of at least one non-polymeric encapsulating agent and at least one excipient, which is acceptable in nutraceutical, food, cosmetic and pharmaceutical industry. Turmeric formulation is granular, free flowing and exhibits non-colouring property, wherein it does not stain the surfaces in contact and also does not cause dusting and impart any coloration to the equipment or formulation area while converting the granules in desired dosage forms. The invention also relates to the process for preparation of non-colouring formulation, wherein the blend of turmeric powder and curcumin extract may be granulated using at least one excipient and the granules are encapsulated with at least one non-polymeric agent using suitable equipment. The process for preparation is simple, cost effective and environment friendly. The granular formulation retains characteristic bright colour of turmeric, however it does not leach out colour of the active, while converting into various solid and semisolid dosage forms, thus avoiding the need for frequent intermittent cleaning process and is industrially useful and convenient for subjecting to various formulation related operations,

Background

Turmeric (Curcuma longa) is used as a spice, preservative, colouring matter and has wide range of medicinal and pharmacological applications. It exhibits anti inflammatory, anti-HIV, anti-bacterial, antioxidant, nematocidal, antiparasitic, antispasmodic and anticarcinogenic activities. It is a potent scavenger of a variety of reactive oxygen species (ROS) including superoxide anion, hydroxyl radical, singlet oxygen, peroxynitrite and nitric oxide. It plays a active role in the inhibition of COX- I and COX-II enzymes that are involved in the inflammatory reaction. It prevents oxidative damage and inhibits binding of toxic metabolites to DNA. Turmeric contains 3-6% polyphenolic compounds, collectively known as curcuminoids, which is a mixture of curcumin, demethoxycurcumin and bisdemethoxycurcumin. Curcuminoids are major components responsible for various biological actions. However, some studies suggest that turmeric powder has significant health benefits, and it's possible that it has benefits that curcumin alone doesn't, but most possibly because of presence of fibres and essential oils as well.

In Asian countries, fresh and dry turmeric rhizomes as well as ground turmeric is used for vegetable and meat dishes and soup-like products. Turmeric powder as well as rhizome has been also used in food and Ayurvedic medicines since thousands of years for its medicinal properties in liver disorders, and wide variety of pulmonary, gastrointestinal and skin diseases. It keeps skin soft and smooth, makes it glow, tackles acne and helps treat hyper-pigmentation. Turmeric paste is also prescribed in Indian medicine for various skincare issues, like puffiness, wrinkles and eczema. Besides this, it is used for cuts and burns due to its antiseptic effect and ability to promote healing. In addition, it can help to decrease muscle soreness after an intense workout.

Even though there has been an increasing interest in turmeric due to its medicinal properties over the past few years, handling or processing of this product in regular powder form is a big problem due to its amorphous nature, poor flow properties, along with staining and dusting properties. Turmeric powder as well as curcumin extract stain the equipment and contact surfaces, while handling it or formulating in dosage forms, and therefore make the production process troublesome and time consuming. Turmeric powder as well as curcuminoids also cause dusting in the formulation area and therefore the entire plant needs complete change over cleaning, which is very often done using organic solvents, thus involves considerable cost, time and therefore affecting the production efficiency.

Prior art patent applications in this subject area are mainly focused on either use of hydrophilic natural polymers or use of various catalytic or other hydrogenation reactions to get non- staining curcuminoid formulations. IN201402079 describes a process for preparation of glycosylated tetrahydrocurcumin, which is a major colourless metabolite of curcuminoids isolated from Curcuma longa. The process was comprised of glycosylation process and use of a phase transfer catalyst. Tetrahydrocurcumin-di-P-glycoside was synthesized, and its biological and pharmacological activity was evaluated. The accelerated wound-healing process with non-toxic, non-irritant and non-staining properties render this multi-functional compound tetrahydrocurcumin-di-P-glucoside as a useful ingredient in achromatic food and cosmetic applications.

US20180042858 describes a non-bleeding curcumin composition comprising curcumin and a coating polymer wherein the polymer is selected from the group consisting of a biopolymer, synthetic polymer or a mixture thereof. The biopolymer is selected from the group consisting of cellulose, shellac, galactomannans, glucomannans, arabinoxylans, natural gums, proteins or a mixture thereof and the synthetic polymers is selected from the group consisting of polyvinyl alcohol, polylactic acids or a mixture thereof. The non-bleeding curcumin composition eliminate the problems of colour bleeding, colour leaching, colour staining and dusting during the industrial processing of curcumin.

US8568802 describes composition with enriched fraction of tetrahydroxy curcumin and its tetrahydro analogs, comprising tetrahydroxy curcumin, demethyl curcumin, dimethyl monodemethoxy curcumin and bisdemethoxycurcumin. The said enriched fraction of tetra hydroxycurcumin is subjected to hydrogenation to get colourless tetrahydroxy curcumin enriched fraction. The enriched fractions of tetrahydroxy curcumin and colourless tetrahydro tetra hydroxycurcumin exhibits potent antioxidative action and reduces inflammation.

US20170258743 describes process of preparation of white curcumin wherein the process comprises of treating curcuminoids with ethyl acetate to form a reaction mixture and adding palladium carbon as catalyst to the reaction mixture and allowed for hydrogenation in the presence of hydrogen gas. the reaction mixture is filtered and washed with ethyl acetate. The ethyl acetate is distilled to obtain a crude mass of white curcumin. Prior art references mainly focus on chemical modification of curcuminoids through demethylation or hydrogenation or physical masking of colour through polymeric coating of curcuminoids by using synthetic or natural excipients for overcoming the problem of colour staining and dusting during industrial processing of curcuminoids. However, this may result into chemical transformation of curcuminoids along with change in its natural bright yellowish orange colour, which may not be desired for application in nutraceutical, food and cosmetic industry. Further the polymeric coating of curcuminoids for colour masking depends on percentage of coating excipient applied on the active and evenness of the coating. Slight rupture of coating during handling or processing may result into staining of the contact surfaces, formulation area and the equipment.

Summary

There is an unmet need to find out alternate ways to overcome the staining property of turmeric, without disturbing or disrupting its chemical identity, physical characteristics as well as original colour, thus making the product acceptable and suitable for foods, cosmetic and nutraceuticals applications. Moreover, it would be preferable, if turmeric powder can be used in blend with curcumin extract, to get entire spectrum of the benefits from all the constituents present in turmeric powder as well as the extract.

The researchers of the present invention have carried out extensive experimentation using a blend of turmeric powder and curcumin extract, which was successfully converted into a non-colouring formulation of turmeric. It was surprisingly found that, with proper selection and optimization of encapsulating agents as well as process, the researchers could convert blend of turmeric powder and curcumin extract into coated granular and free flowing, which exhibits non-colouring property, wherein it does not cause any staining, colouring, or dusting while handling the granules for processing or converting into finished dosage form. Turmeric powder, which is otherwise highly amorphous in nature and has very poor flow and characteristic staining properties, could be successfully converted into a formulation, which does not leach out even during compression process into tablet dosage form; while still retaining its characteristic colour. The granular formulation is prepared by using a combination of excipient and encapsulating agent, resulting into excellent flow and non-colouring property, which makes it suitable and convenient for converting into solid and semisolid dosage forms. The process employed by the researchers of the invention for encapsulation is carried out at controlled heat condition, wherein the molten non polymeric encapsulating agent is applied to fluidized granules using suitable equipment. The non-colouring turmeric formulation, as described herein is comprised of a blend of turmeric powder and curcumin extract in various ratios, ranging from 50:1 to 5:1, thus incorporating wide spectrum of constituents from both the counterparts in the granular form, which is very useful for applications in food, nutraceuticals, pharmaceutical as well as cosmetics industry.

None of the prior art references describe a blend formulation of turmeric powder and curcumin extract, as described herein, which possesses excellent flow and exhibits non-colouring property, while retaining characteristic colour of turmeric.

Objectives

The main objective of the invention is to provide a non-colouring, free flowing and granular formulation comprising turmeric powder, which does not cause dusting or staining of the contact parts, equipment, or formulation area, while processing into final dosage form.

Important objective of the invention is to provide a non-colouring formulation, comprising turmeric powder, which retains its characteristic colour; but does not leach it out even during the compression of granules into compressible dosage forms or conversion in other suitable solid and semisolid dosage forms.

Another objective of the invention is to provide the turmeric formulation, wherein the blend of turmeric powder and curcumin extract may be used in various ratios ranging from 50: 1 to 5:1.

One more objective of the invention is to provide a granular, non-colouring formulation comprising blend of turmeric powder with curcumin extract and at least about 10% to 25% by weight of non-polymeric encapsulating agent or a combination thereof.

One objective of the invention is to provide a non-colouring turmeric formulation comprising turmeric powder, a non-polymeric encapsulating agent and at least one excipient, which is acceptable in nutraceutical, food, cosmetics and pharmaceutical industry.

One important objective of the present invention is to provide a process for preparation, wherein blend of turmeric powder with curcumin extract may be granulated using at least one excipient and the granules may be encapsulated with a non-polymeric agent using suitable equipment.

One objective of the invention is to provide a non-colouring granular formulation of turmeric, wherein the granule size may range from 100 microns to 900 microns.

One important objective of the formulation is to provide a turmeric formulation, which can be converted into various solid and semisolid dosage forms without staining, dusting or colouring the contacting body parts, surfaces, working area and equipment.

Description of the Figure

Figure 1 demonstrates the evaluation of non-colouring property of the turmeric formulation, wherein the granular formulation is compressed into tablet dosage form, and it does not colour any of the compression equipment, even after carrying out the compression process for about 4 hours.

Figure 2 demonstrates structural elucidation of encapsulated granules, which is carried out using scanning electron microscopy of cross-section surfaces of granules. It indicates uniform coating of granules by non-polymeric encapsulating agent, which is confirmed through measurement of coating thickness in microns.

Detailed Description

The invention relates to a non-colouring turmeric formulation, which is comprised of a blend of turmeric powder with curcumin extract in various ratios, ranging from 50: 1 to 5:1. The formulation is also comprised of about 10% to 25% by weight of a non- polymeric encapsulating agent and at least one excipient which is acceptable in food, nutraceutical, cosmetic and pharmaceutical industry. Turmeric formulation, as described herein, may be comprised of about 2% to 20% of total curcuminoids. The invention also relates to a process for preparation of turmeric formulation, wherein turmeric powder or its the blend with curcumin extract is granulated using at least one excipient and the resulting granules are treated with a non-polymeric encapsulating agent to get a non-colouring, free flowing formulation, thus, incorporating wide spectrum of constituents from both the counterparts in the granular form, which is very useful for applications in food, nutraceuticals as well as cosmetic industry.

The present invention employs blend of turmeric powder with curcumin extract, both of which are derived from Curcuma species of the Zingiberaceae (ginger) family.

The term ‘turmeric powder’ as used herein means the powder obtained from roots, tubers or rhizomes of the Curcuma species of the Zingiberaceae (ginger) family including but not limited to species like Curcuma longa, Curcuma amada, Curcuma angustifolra, Curcuma caesia, Curcuma zedoaria, Curcuma caulina, Curcuma aromatica, Curcuma wenyujin, Curcuma xanfhorrhiza, Curcuma phaeocaulis, Curcuma leucorrhiza and Curcuma kwangsiensis.

It is light yellow to yellowish orange in colour and also has characteristic odour and taste. Seasonal and geographical variation may bring some changes to the colour shade of turmeric powder in the range of light yellow, yellow, orangish yellow to yellowish orange, although the basic shade remains common in general, which is very characteristic to curcuma species. It contains at least about 2% of the curcuminoids along with essential oil, fibers and other natural components. Turmeric powder is very fine in size, amorphous in nature and exhibits poor flow. It tends to generate lots of dusting and results in staining of the processing area, equipment and contact surfaces due to its fine particle size and characteristic colour. Complete cleaning and changeover of the area, clothes and equipment is therefore required after processing any turmeric product, resulting into wastage of time, money and use of costly organic solvents. The present invention provides a granular, free flowing and non-coloring formulation of turmeric powder which overcomes all processing difficulties of turmeric powder and provides an ingredient formulation, which can be conveniently converted in required solid and semisolid dosage forms like tablets, caplets, capsules, stick packs, creams, ointments and other suitable dosage forms as per the requirement.

The term ‘curcumin extract’ is used herein to mean the extract of roots, tubers or rhizomes of the Curcuma species of the Zingiberaceae (ginger) family including but not limited to species like Curcuma longa, Curcuma amada, Curcuma angustifolra, Curcuma caesia, Curcuma zedoaria, Curcuma caulina, Curcuma aromatica, Curcuma wenyujin, Curcuma xanfliorrhiza, Curcuma phaeocaulis, Curcuma leucorrhiza and Curcuma kwangsiensis.

Curcumin extract is comprised of curcumin (diferuloylmethane), desmethoxycurcumin, or bisdesmethoxycurcumin, including their polymorphs, hydrates, solvates, derivatives, and mixtures thereof. Curcumin extract is a yellowish orange coloured fine powder with characteristic odour and taste, although geographical and seasonal variations may bring change in colour shades. It is comprised of at least about 95% w/w of curcuminoids, calculated in the form of curcumin, desmethoxycurcumin and bisdemethoxycurcumin, including their polymorphs, hydrates, solvates, derivatives, and mixtures thereof.

The terminology ‘blend’ as used herein means the uniform mixture of two active components employed in the non-coloring formulation. The blend is comprised of turmeric powder and curcumin extract. The non-coloring formulation as described herein, may be comprised of blend of turmeric powder and curcumin extract in various ratios ranging from 50:1 to 5:1. More preferably, the formulation may be comprised of blend of turmeric powder and curcumin extract in ratio ranging from 45: 1 to 6:1, as per the requirement. The formulation may also be comprised of turmeric powder alone, which is converted in the form of granules by using the process, as described herein. The formulation may be comprised of about 2% to 20% of total curcuminoids, as obtained from turmeric powder alone or the blend of turmeric powder and curcumin extract. The formulation may preferably be comprised of about 5 to 15% by weight of total curcuminoids in granular form.

The terminology ‘non-coloring’ as used herein means property of the granular formulation of turmeric powder, as described herein, by virtue of which, it does not confer its yellow to yellowish orange colour, which is characteristic of unformulated turmeric powder, to any of the contact surfaces or equipment, while processing into finished dosage forms. Thus even if the granules come in contact with equipment while carrying out processes like weighing, mixing, blending, filling and so on, these equipment do not get stained and also the formulation area does not get dusted due to turmeric powder in granular composition. Even though the composition is prepared from the blend of turmeric powder and curcumin extract, which have very peculiar and characteristic yellow to yellowish orange colour, the formulation exhibits non coloring characteristic, in its granular form.

The terminology ‘yellow to yellowish orange’ as used herein refers to colour range of turmeric powder and curcumin extract, wherein the colour may vary from different shades of yellow to red to orange. The shade of turmeric powder as well as curcumin extract may vary depending upon source, processing conditions, storage conditions, but the spectrum of colour shade may vary from bright yellow, light yellow to light orange or reddish orange or dark yellowish orange. The granular non-coloring formulation as described herein retains the colour shade of unformulated turmeric powder or blend of turmeric powder and curcumin extract; but does not stain or color the contact surfaces, while processing into final dosage forms.

The terminology ‘non-polymeric encapsulating agent’ as used herein refers to the agent or excipient employed in the non-coloring formulation, for covering the granules comprising turmeric powder or its blend with curcumin extract. It covers and or encapsulates the granules, to confer the non-coloring property. It also acts as a seal coating and provides the protection to core granules from ingress of moisture and other gases. The formulation as described herein, may be comprised of at least about 10-25% by weight of non-polymeric encapsulating agent.

Non-polymeric encapsulating agent may be selected from the group of lipids, fats, fatty acids, fatty alcohols, fatty acid esters, waxes, and the combination thereof.

Fats, which are used for the embodiments of the present invention, consist of a wide group of compounds that are generally soluble in organic solvents and largely insoluble in water. Hydrogenated fats (or saturated fats) in the context of the present invention are generally triesters of glycerol and fatty acids. Fatty acids are chains of carbon and hydrogen atoms, with a carboxylic acid group at one end. Such fats can have natural or synthetic origin. It is possible to hydrogenate a (poly)unsaturated fat to obtain a hydrogenated (saturated) fat.

As per one more embodiment, the non-polymeric encapsulating agent may be selected from, but not limited to, saturated fatty acids having 12 to 28 carbons, such as stearic acid, palmitic acid, fatty alcohols having from 16 to 44 carbons, cetyl alcohol, soya fat, pegylated fatty acids, glycerol fatty acid esters, derivatives of mono-diglycerides, glyceryl behenate, glyceryl monostearate, glyceryl palmitostearate, phosphatides, cerebrosides, gangliosides, cephalins, lipids, glycolipids, sulfatides, sugar esters, sugar ethers, sucrose esters, sterols, polyglycerol esters, glycerolipid, phosphatic acid, phosphatidylethanolamine, phosphatidylserine, or other glycerophospholipids, ceramide, sphingolipid, sterol, fat-soluble vitamin, prenol, saccharolipid, polyketide, their salts and esters and the combination thereof.

Waxes in the context of the present invention are organic compounds that characteristically consist of long alkyl chains. Natural waxes (plant, animal) are typically esters of fatty acids and long chain alcohols. Synthetic waxes are long- chain hydrocarbons lacking functional groups. The encapsulating agent, as described herein may also be selected from, but not limited to, beeswax, candelilla wax, carnauba wax, spermaceti, paraffin wax, synthetic waxes and the combination thereof.

Preferred examples of fats suitable for the present invention are glycerine monostearate, stearic acid, hydrogenated cottonseed fat, hydrogenated palm fat and hydrogenated rapeseed fat, hydrogenated palm fat, hydrogenated soyabean fat, hydrogenated sunflower fat, hydrogenated rapeseed fat, soya fat, palmitic acid. These compounds can be used as such or as mixtures.

As per one embodiment of the invention, non-colouring formulation may be comprised of 1% to 20% by weight of excipients, which are acceptable in food, nutraceutical, cosmetics and pharmaceutical industry. Excipients may facilitate the granulation of turmeric powder or its blend with curcumin extract. The excipient may also facilitate conversion of granule formulation in desired dosage form, suitable for administration.

These are commonly used ingredients in industry, and are selected from the group of, but not limited to, fillers, diluents, disintegrants, lubricants, binders, glidants, anti caking agents, stabilizers, surfactants, channelizing agents, vehicles, buffers, stabilizers, preservatives, acidifiers, alkalizers, complexing agents, gum bases, antioxidants, viscosity enhancers, plasticizers, coating materials, and the combination thereof.

The excipients may belong to the class such as polymeric, non-polymeric, swelling, non-swelling, pH dependent and pH independent additives. The non-colouring turmeric formulation, as described herein, may be comprised of about 1 to 20% by weight of additives, which are selected from natural, semi-synthetic or synthetic sources. More preferably, the formulation may be comprised of about 1 to 15% by weight of excipients.

The formulation may be comprised of diluents known in the art, but not limited to microcrystalline cellulose, silicified microcrystalline, cellulose, powdered cellulose, microfine cellulose, corn starch, rice bran extract, calcium phosphate, dibasic calcium phosphate, tribasic calcium phosphate, calcium sulfate, or mixtures thereof. The diluents may also be selected from glucose, lactose, sucrose, dextrose, fructose, compressible sugar, or mixtures thereof.

The binders may be selected from the group of cellulose derivatives such as hydroxypropylmethyl cellulose (HPMC), hydroxypropyl cellulose (HPC), ethylcellulose, carboxymethylcellulose (CMC), sodium CMC, potassium CMC, calcium CMC, methylcellulose, hydroxyethyl cellulose (HEC), microcrystalline cellulose; polyvinylpyrrolidone (PVP), vinyl pyrrolidone-vinyl acetate copolymer, polyvinyl alcohol, starch, carbomer, gums like xanthan gum, guar gum, acacia, locust bean gum, alginates, or mixtures thereof.

The disintegrants may be selected from sodium starch glycolate, crospovidone, croscarmellose sodium, croscarmellose calcium, croscarmellose potassium, sodium carbonate, sodium hydrogen carbonate, calcium carbonate, starch, starch 1500, modified starch, pregelatinized starch, crosslinked carboxymethyl starch, sodium hydrogen carbonate, hydroxypropyl cellulose, sodium carboxymethylcellulose or mixtures thereof.

According to one embodiment of the invention, the formulation may be prepared by using blend of turmeric powder and curcumin extract, which can be prepared by mixing both the powder components well using a suitable blender and/or mixer. Turmeric powder may be mixed with curcumin extract in different ratios, ranging from 50:1 to 5:1, to give rise to different variants of the non-colouring turmeric formulation.

As per another embodiment of the invention, turmeric powder or its blend with curcumin extract can be granulated using at least one excipient, employing various granulation processes known in the art such as dry granulation, wet granulation, melt granulation, extrusion spheronization, coacervation, congealing, reverse wet granulation, steam granulation, freeze granulation, foam granulation and the like.

According to one embodiment of the invention, the granules may be prepared by single step or multi-step granulation, using various suitable granulation equipment such as rapid mixer granulator, liquid mixer granulator, oscillating granulator, ribbon mixer granulator, extrusion spheronizer, hot melt extruder, roller compactor, fluid bed granulator, which are generally used in food, nutraceutical, cosmetics or pharmaceutical industry.

More preferably, the formulation may be prepared by wet granulation process using a binder and the agglomerates can be dried and sieved through suitable sieve to get the granules of desired size. The granules may be treated with a non-polymeric encapsulating agent using controlled process conditions employing suitable coating equipment such as tangential fluid bed dryer, fluidized bed processor, bottom spray fluid bed drier or top spray fluid bed drier, rotary plate drier with circular, elliptical and fish gill like holes, or employing blenders like ribbon blender or using pan coaters to get a non-colouring turmeric formulation.

Preferably, the formulation may be prepared by using a combination of at least one excipient and a non-polymeric encapsulating agent, wherein the excipient such as binder or diluent is used to convert the blend into agglomerates, which are converted in granules. The granules may be treated with non-polymeric fatty encapsulating agent using controlled conditions of heat, wherein the encapsulating agent is applied to fluidized granules in the form of fine droplets under the current of air, using suitable equipment. The encapsulating agent may be applied on granules in multiple unform layers to offer non-colouring property.

The formulation of the invention was evaluated for flow property, assay content, stability, non-colouring property, and microbial content. The formulation was also subjected to Scanning Electron Microscopy (SEM) characterization for structure elucidation of encapsulated granules, in order to check uniformity of coating on the granules.

The non-colouring turmeric granules, as described herein are prepared by using non- polymeric encapsulating agent, which acts as an effective seal coating agent. The coating may also offer very good protection from microbial load as the microbes can’t survive in fat medium at the temperature employed for the purpose of coating or encapsulation. The surface of granules may get stabilized during the process of encapsulation, resulting in considerable reduction in the microbial load, which might have got introduced from turmeric powder.

Granular formulation prepared by the process as described herein, retains the characteristic yellowish orange colour the active even after the granulation, but it exhibits non-colouring and non-dusting property. As per this property, the granules avoid staining and dusting of yellowish orange colour, while processing it in finished dosage form. The granular non-colouring formulation of turmeric powder as described herein exhibits excellent flow property and it may overcome process difficulties such as bulk handling of turmeric powder and/or curcumin extract, and overcomes the problem of colour explosion and dusting characteristics, which may make the formulation production troublesome, expensive and time consuming because of complete change over cleaning required using organic solvents after manufacturing the batches.

The composition as described herein is prepared by using environment friendly solvent for granulation and a non-polymeric encapsulating agent. The granules prepared by this process overcome the tedious problems of staining of the equipment and other contact surfaces and therefore are useful for formulation into finished dosage forms.

The granular formulation, as described herein, can be used as directly compressible grade granules, which can be compressed in tablets, without adding any other excipient like diluent, filler or binder and the combination thereof. This property adds to the industrial usefulness of the formulation, for converting the granules in tablet dosage forms, by retaining the percentage of active constituent, without diluting if further by addition of any excipients for compression purpose.

The non-colouring granular formulation as described herein has various advantages with respect to industrial processing. The formulation is comprised of turmeric powder or the blend of turmeric powder and curcumin extract, which combines whole spectrum of active constituents present in turmeric powder and the curcumin extract, such as curcuminoids, turmeric oil, and fibres, thus offering additional benefits to the consumers. Turmeric oil may offer advantage with respect to enhanced solubility and absorption of the formulation in the body system. Non-colouring formulation of the invention can be converted into tablets, capsules and other dosage forms by using suitable excipients, processes and equipment employed in nutraceutical, pharmaceutical or food industry. The granules do not stain the equipment used in the processing, thus making the formulation process convenient and industrially useful.

This data is presented, along with illustration in the form of non-limiting examples in the patent specification. Examples

Example 1: Non-colouring formulation comprising Turmeric powder: Curcumin extract (15:1)

Table 1: Composition of non-colouring turmeric formulation

*q.s. in the table indicates quantity sufficient.

Process for preparation:

Turmeric powder and curcumin extract are dry mixed in suitable blender equipment to obtain a uniform blend. The binder comprising of starch paste is introduced into the blend to obtain agglomerates. These are dried and screened through the sieve to obtain granules of the desired size. The turmeric granules are encapsulated using molten hydrogenated palm stearin fat in the pan coater at temperature of about 30-55° C to get light to dark yellowish orange colour product, which is free flowing and exhibits non-colouring property.

Example 2: Evaluation of non-colouring property of turmeric granule formulation

The non-colouring property of turmeric granules obtained by the process disclosed in example 1 was evaluated during the compression in tablet dosage form. The formulation, which was obtained in the form of directly compressible grade (DC grade) granules was subjected to the process of continuous tabletting for about 4 hours in a single rotary, 16 station tablet compression machine using a caplet size punch, which is oval, standard concave and plain on both sides.

Various parameters such as weight variation, hardness, thickness, friability of the compressed tablets were evaluated as a part of in-process quality check (IPQC) and the results were tabulated in Table 2.

Table 2: Evaluation of tablet comprising non-colouring turmeric granules

It was observed from Figure 1 that there was no staining or colouring of the equipment like dies, punches, punch guide, turret, or any other part of the tabletting machine, while the granules were subjected to the tablet compression process for almost 4 hours. Further, the formulation did not cause any dusting of the compression area or the contact parts, while it was being processed into tablet dosage form. Thus, the non colouring formulation of turmeric is industrially useful for converting the free-flowing granules in suitable compressible finished dosage forms.

Example 3: Stability study of granules of Example 1

Free flowing granules of Example 1 were subjected to accelerated stability study in a tri-laminated aluminium pouch and the assay evaluation was carried out using HPLC analysis to understand the content of active over 6 months at standard condition of temperature and humidity. The granules were also evaluated for microbial load during stability study and the results of evaluation are tabulated in Table 3.

Table 3: Evaluation of granules during Accelerated stability study

It was observed that the granules prepared by process of Example 1 were stable over 6 months, under accelerated stability conditions and also the microbial load of the formulation was within acceptable limits for all variety of microbes mentioned in the table.

Example 4: Non-colouring formulation comprising turmeric powder:

Curcumin extract (9:1)

Table 4: Composition of non-colouring Turmeric formulation

Process for preparation:

Turmeric powder and curcumin extract are dry mixed in suitable blender equipment to obtain a uniform blend. The binder comprising of starch paste is introduced into the blend to obtain agglomerates. These are dried and screened through the sieve to obtain granules of the desired size. The turmeric granules are encapsulated using molten hydrogenated palm stearin fat in the pan coater at temperature of about 65-70° C. The granules are compressed in tablets for evaluation of curcuminoid contents.

Evaluation of curcuminoid content in tablet comprising non-colouring turmeric granules

The curcuminoid content of the non-colouring turmeric granules of example 4 were evaluated by HPLC evaluation using a tetrahydrofuran : citric acid anhydrous buffer mobile phase. The solution of working standard and test sample were prepared in methanol and injected in the system for determining the content of total curcuminoids, curcumin, desmethoxy curcumin and bisdesmethoxy curcumin.

Table 5: HPLC determination of Curcuminoids in tablet formulation

Example 5: Non-colouring formulation comprising turmeric powder: turmeric extract (45:1)

Table 6: Composition of Non-colouring Turmeric formulation

Process for preparation:

The turmeric powder and curcumin extract are dry mixed in suitable blender equipment to obtain a uniform blend. The binder comprising of starch paste is introduced into the blend to obtain agglomerates. These are dried and screened through the sieve to obtain granules of the desired size. The turmeric granules are encapsulated using molten hydrogenated palm stearin fat in the pan coater at temperature of about 65-70° C.

Example 6: Non-colouring formulation comprising turmeric powder: curcumin extract (5:1)

Table 7: Composition of non-colouring turmeric formulation

Process for preparation:

Turmeric powder and curcumin extract are dry mixed in suitable blender equipment to obtain a uniform blend. The binder comprising of starch paste is introduced into the blend to obtain agglomerates. These are dried and screened through the sieve to obtain granules of the desired size. The turmeric granules are encapsulated using molten hydrogenated palm stearin fat in the pan coater at temperature of about 65-70° C.

Example 7: Evaluation of Coating Uniformity of Non-colouring Turmeric formulation

The turmeric granules are coated with molten hydrogenated palm fat solids using hot melt technique. The encapsulation may be carried out under the current of air by spraying fine droplets molten fat in a fluidized bed processor.

The images of the cross-section view of encapsulated turmeric granules, as seen through scanning electron microscope are disclosed in the Figure 2.

Table 8: The wall thickness of the turmeric granules measured through electron microscope

It is evident from Table 9 A to D that wall thickness of individual fat layers was measured in the range of 5.93 pm to 17.24 pm, thus average thickness was about 11.0 pm. The thickness measurement, as obtained from analysis of the images indicated that the coating was uniform on turmeric granules, thus exhibits the encapsulation efficiency of the coating agent, which resulted in non-colouring turmeric formulation.

Example 8: Evaluation of non-colouring property of turmeric granules

The non-colouring property of the formulation, as described herein was evaluated by comparative study wherein, effect of both the granular formulation and unformulated turmeric blend (turmeric powder and curcumin extract mixture in the same ratio as used in the formulated non-colouring product) on contact surface and the difference in the extent of cleaning required during processing of both the product was checked using equipment plate, followed by visual observation and UV absorbance of rinse solution at 420nm.

Non-colouring turmeric granular formulation was spread evenly on a steel plate and the product was removed on the butter paper. The plate was rinsed with methanol and the rinsate was analysed using UV absorbance at 420 nm. The same procedure was repeated for unformulated turmeric blend formulation and the number of rinsates were analyzed using UV spectrophotometer.

Table 9: Assay of Total Curcuminoids from Rinsate Solution

Table 10: Evaluation of non-colouring property of Turmeric granules

It is evident from above photographs, visual observation and the analysis that the formulation of turmeric blend exhibits non-colouring property as compared to unformulated turmeric blend and the cleaning time required for the formulation is significantly less than that required for unformulated turmeric blend.

It was seen that formulated turmeric blend granules are 116 times less staining than unformulated turmeric blend powder. Also the formulation, as described herein needs maximum 2 times rinsing to clear off the contact surface, in comparison to 4 rinsing required for unformulated turmeric blend, in order to get zero reading for total curcuminoids on UV Spectrophotometer at 420 nm. Thus the non-colouring formulation requires less number of washings to clean the contact surfaces or the equipment, as compared to the unformulated turmeric blend powder, which required multiple cleaning cycles, in order to clean the contact surface and equipment, before switching over to another product in the processing area. Non-colouring turmeric formulation, as described herein is thus convenient to process, involves less time and cost for cleaning the equipment and switching over to another product. It does not stain the contact surfaces and avoids dusting in the formulation area, thus proves to be industrially useful. The formulation is free flowing and can be conveniently converted in suitable compressible and other dosage forms, as per requirement.

Claims

1. A non-colouring turmeric formulation, comprised of blend of turmeric powder and curcumin extract, at least one non-polymeric encapsulating agent and at least one excipient which is acceptable in nutraceutical, food, cosmetic and pharmaceutical industry.

2. The non-colouring turmeric formulation of claim 1, which is comprised of blend of turmeric powder and curcumin extract varying in the range of 50: 1 to 5:1.

3. The non-colouring turmeric formulation of claim 2, which is comprised of about 2 to 20% by weight of total curcuminoids.

4. The non-colouring turmeric formulation of claim 1, which is comprised of about 10 to 25% by weight of at least one non-polymeric encapsulating agent.

5. The non-colouring turmeric formulation of claim 4, which is comprised of at least one non-polymeric encapsulating agent selected from the group of lipids, fats, fatty acids, fatty alcohols, fatty acid esters, waxes, and the combination thereof.

6. The non-colouring turmeric formulation of claim 1, which is comprised of about 1 to 20% by weight of at least one excipient, which is acceptable in nutraceutical, food and pharmaceutical industry.

7. The non-colouring turmeric formulation of claim 6, which is comprised of at least one excipient, selected from the class of fillers, diluents, disintegrants, lubricants, binders, glidants, anti-caking agents, stabilizers, surfactants, channelizing agents, vehicles, buffers, stabilizers, preservatives, acidifiers, alkalizers, complexing agents, gum bases, antioxidants, viscosity enhancers, plasticizers, coating materials, and the combination thereof.

8. The process for preparation of non-colouring turmeric formulation, which is comprised of

• mixing well turmeric powder and curcumin extract in desired ratio, varying in the range of 50: 1 to 5: 1 to get a blend • granulating the blend of turmeric powder and curcumin extract, using at least one excipient, which is acceptable in neutraceutical, food and pharmaceutical industry, to get the granules

• encapsulating the agglomerates with at least one non-polymeric encapsulating agent selected from the group of lipids, fats, fatty acids, fatty alcohols, fatty acid esters, waxes, and the combination thereof; using suitable equipment to get free flowing and non-colouring turmeric granules

• converting the granules in desired solid or semisolid dosage forms or filling the granules in sachets, capsules for convenient administration to the subjects.

9. The process of non-colouring turmeric formulation of claim 8, wherein the granules range in size from 100 microns to 900 microns.

10. The non-colouring turmeric formulation of claim 1, which does not stain the contact surfaces and does not cause dusting and impart any colouration to the equipment and the formulation area, while processing and converting into suitable dosage forms.