Title of Invention

A METHOD OF PREPARING FREE FLOW FLOWABLE DIRECT COMPRESSIBLE CAROTENOID POWDER FORMULATION

Abstract

A free flowable directly compressible powder formulation consisting maltodextrin as diluent, as binder and as filler where it yields very hard tablets at relatively low compression forces. Maltodextrin has substantially reduced the number of steps in obtaining free flowing direct compressible carotenoid powder. More the number of steps, greater the chance of degradation. Croscarmellose sodium is added as dissolution accelerator. Expanded silica is added to absorb moisture if any during the processing of the powder. Ascorbic acid is added to add stability to the product The flowability is attained by coating the powder uniformly with ethyl cellulose. This coating provides excell^t protection to the ndxed carotenoids and functions as glidant and lubricant, thus avoiding a use of an additional lubricant. Free flowing powder has excellent tabletting characteristics, good stability with very good dissolution property. The free flowable powder can also be filled directly in hard gelatin capsules.

Full Text

The present invention relates to a method of preparing free flowable direct compressible carotenoid powder formulations In the said invention the use of maltodextrin as a carrier for manufacture of direct compressible powder forms for the purpose of oral dosage forms such as tablet or capsules. The innovation contains the use of maltodextrin as a diluent, filler and binder and reducing the number of steps as in various technologies wherein starch or lactose are used. The use of a single ingredient for the functions cuts cost and time of production. Another object of the present inventions is enable to simultaneously obtained the microencapsulation of carotenoids giving it stability. The other novelty in this formulation is the use of ethyl cellulose for coating. This replaces lubricants, which are needed during tabletting, and acts as a glidant. This ensures that the product can be successfully used in directly filling in hard gel capsules. The other function of ethyl cellulose is forming a thin film over the carotenoids protecting it from exposure to oxygen. These multiple functions of maltodextrin and ethyl cellulose renders a very stable direct compressible free flowing powder. References Cited U.S. Patent Documents 3034911 May., 1962 McKee et al. 106/210. 3490742 Jan., 1970 Nichols etal. 252/99. 3622677 Nov., 1971 Short et al. 424/361. 3956515 May., 1976 Moore et al. 426/302. 4072535 Feb., 1978 Short etal. 106/210. 4369308 Jan., 1983 Trubiano 536/106. 4383111 May., 1983 Takeoetal. 536/102. 4384005 May., 1983 McSweeney 426/250. 4551177 Nov., 1985 Trabiano et al. 106/210. 5164014 Nov., 1992 Brancqetal. 127/32. 5560927 Oct., 1996 Menonetal. 424/464. Other References Sakurai, Y (ed.), "Food General Dictionary" Sixth Edition (The English translation is 10 pages total.). Handbook of Natural Materials for Food Processing, Ninth Edition (Translation to be disclosed at a later date). Chemical Dictionary, 7.sup.th Edition (Translation to be disclosed at a later date). Pogany et al., "A new approach to the theory of tabletting" Acta Pharm. Hung. (1988) 58:49-55. Doelker, "Recent advances in tableting science" Boll. Chim. Farm. (1988) 127:37-49. Hiestand et al., "Physical processes of tableting" J. Pharm. Sci. (1977) 66:510-519. Niwa et al., "Preparation of agglomerated crystals for direct tabletting and microencapsulation by the spherical crystallization technique with a continuous system" Pharm. Res. (1994) 11:478-484. Lipps et al., "Characterization of wet granulation process parameters using response surface methodology. 1. Top-spray fluidized bed" J. Pharm. Sci. (1994) 83:937-947. Paronen et aL, "Compressional characteristics of four starches" J. Pharm. Pharmacol. (1983) 35:627-635. Naito et al., "Prediction of tableting problems such as capping and sticking: Theoretical calculations" J. Pharm. Sci. (1977) 66:254-259. Healey et al., "The mechanical properties of some binders used in tableting" J. Pharm. Pharmac. (1974) 26 Suppl:41P-46P. York et al., "The effect of temperature on the mechanical properties of some pharmaceutical powders in relation to tableting" J. Pharm. Pharmac. (1972) 24 Suppl:47P-56P. Sebhatu et al., "Effect of moisture sorption on tabletting characteristics of spray dried (15% amorphous) lactose" Pharm. Res. (1994) 11:1233-1238. The state of art: Active agents like vitamins, carotenoids, and other pharmaceuticals are most frequently administered orally by means of solid dosage forms such as tablets and capsules. Large scale production methods used for their preparation usually require that they contain other materials in addition to the active ingredients. Additives may also be included in the formulations to facilitate handling, enhance the physical appearance, improve stability and aid in delivery of the drug to the bloodstream after administration. Tablets are defined as solid dosage forms containing active agents of different origin such as vitamins, enzymes and pharmaceuticals with or without suitable diluents. Typically, each tablet contains a single dose of an effective amount of the active agent. Tablets are prepared by compression, extrusion or molding methods. Tablets are popular as a dosage form because of the advantages afforded both to the manufacturer (e.g., simplicity and economy of preparation, stability and convenience in packaging, shipping and dispensing) and the patient (e.g., accuracy of dosage, compactness, portability, blandness of taste and ease of administration). Tablets are the most common form of solid dose drug delivery. For review see, Pogany et al. (1988) Acta Pharm. Hung. 58:49-55; Doelker et al. (1988) Boll. Chim. Farm. 127:37-49; Hiestand et al (1977) J. Pharm. Sci. 66:510-519; and Cooper et al. (1972) J. Pharm. Sci. 61:1511-1555. Compressed tablets may be coated with a variety of substances which may alter their physical characteristics. Sugar coated tablets contain a sugar coating which may be colored. Such coatings are beneficial in masking drugs possessing objectionable tastes or odors and in protecting materials sensitive to humidity, light or oxidation. Film-coated tablets are covered with a thin layer or film of water soluble or insoluble material. A number of polymeric substances with film forming properties can be used. Film coating imparts the same general characteristics as sugar coating with a much shorter period required for coating. Enteric coated tablets are coated with substances that resist dissolution in gastric fluid but disintegrate in the intestine. Enteric coatings are useful for tablets containing drugs that are inactivated or destroyed in the stomach, for those which irritate the mucosa or as a means of delayed release of the medication. Multiple compressed tablets are those made by more than one compression cycle. These include, layered tablets and press-coated tablets. Compressed tablets can be formulated into controUed-release tablets, which release drug over a prolonged period of time to provide pulsatile or sustained release. There are a variety of methods of making compressed tablets. See, e.g., Remington: The Science and Practice of Pharmacy, Nineteenth Edition, Gennaro Ed. (1995) Vol. II pp. 1615-1649; Niwa et al. (1994) Pharm. Res. 11:478-484; and Franz et al. (1980) J. Pharm. Sci. 69:621-628. Interestingly, little has changed since the basic tableting method described in 1843. British Patent No. 9977. A number of parameters must be taken into account in tablet formulation such as moisture content and the physical characteristics of the substituents. This makes tablet formulation somewhat empirical. See, e.g., Lipps et al. (1994) J. Pharm. Sci. 83:937-947; Drissi-Alami et al. (1993) J. Pharm. Belg. 48:43-52; Ishino et al. (1990) Chem. Pharm. Bull. (Tokyo) 38:1987-1992; Sendall et al. (1986) J. Pharm. Pharmacol. 38:489-493; Fetzer et al. (1986) J. Pharm. Pharmacol. 38:254-258; Reading et al. (1984) J. Pharm. Pharmacol. 36:421-426; Paronen et al. (1983) J. Pharm. Pharmacol. 35:627-635; Nakagawa et al. (1982) Chem. Pharm. Bull. (Tokyo) 30:1401-1407; Elsabbagh et al. (1981) Pharmazie 36:488-492; Naito et al. (1977) J. Pharm. Sci. 66:254-259; Healey et al (1974) J. Pharm. Pharmacol. 26 Suppl: 41P-46P; and York et al. (1972) J. Pharm. Pharmacol. 24 Suppl:47P-56P. The selection of a particular formulation of components for use in tableting is determined by a variety of parameters including the physical characteristics of the finished tablet. The exact formulation will contain a number of components, each chosen to impart a specific function and together to effect the specific properties desired in a tablet and is largely determined empirically. The physical characteristics of tablets are measured in terms of strength, friability uniformity of dimensions and disintegration time. Tablet strength, also termed hardness or tensile strength, is a measure of the cohesiveness of a tablet. Hardness is defined as the resistance of the tablet to chipping, abrasion or breakage under conditions of storage, transportation and handling. Partially cold water swellable starches for use as binders and/or disintegrants in the manufacture of tablets by direct compression and as fillers for formulations supplied in hard gelatine capsules, are described in U.S. Pat. No. 3,622,677 and U.S. Pat. No. 4,072,535. The material described is essentially a pre-compacted starch powder obtained by subjecting a non-gelatinised granular starch to physical compaction between steel rollers with the possible input of thermal energy. The compacted starch shows the presence of sharp birefringent granules and non-birefringent granules as well as some aggregates of granules and fragments dried to a moisture content of 9-16%. After the compactation the starch is ground and sieved to yield a free flowing powder. The above mentioned starch powders exhibit limited binding capacity in direct compression and poor disintegration properties. All references cited herein, both supra and infra, are hereby incorporated herein by reference. DISCLOSURE OF THE INVENTION It has now been found that maltodextrin with its various mesh sizes can be used to produce tablets without use of the S-1 process or the necessity of combining all the components. Further, it has also been found that the maltodextrins can^ be successfully incorporated for direct compression powder forms as they have excellent tableting quality and homogeneity. In a normal tabletting protocol various ingredients are added namely lubricants, fillers, gliders, and binders. The present invention encompasses the use of these ingredients by replacing two ingredients which has multiple roles. The maltodextrin used to produce the direct compressible form is not only the diluent, but a microencapsulating agent and a binder. The other ingredient, which aids in the tableting is ethyl cellulose. This acts as a lubricant, glidant and also facilitates in stabilizing the carotenoids by providing a film over it. This property of film formation protects the maltodextrin from absorbing moisture as it is hygroscopic. The other ingredients added are disintegrants like croscarmellose sodium, and moisture absorbants like fused silica, which facilitates free flowability of the powder. Ascorbic acid, an antioxidant is added to the powder to stabilize the carotenoids. The powder has excellent tabletting and disintegration properties. This invention relates to a free-flowing compressible powder suitable for tabletting and direct filling of hard gel capsules, and a process for producing this. Tablets and capsules are amongst the most frequently employed delivery forms for most medicinal preparations. This can be explained by the fact that these dosage forms have a good accuracy of dosage of the added components as in this case the carotenoids. Furthermore, as no liquids are generally involved in the process for preparing these medicinal formulations, handling and packaging are a lot easier. Stability and structural conservation of these preparations are generally better than those of other formulations. It is these qualities that explain the reason why tablets are the most preferred form of media for other applications such as food, nutrition, confectionery products, herbals, and other phytoproducts like carotenoids. This form of delivery with special reference to carotenoids give stability to the product by compression and packaging. Tablets are manufactured using three main processes, wet granulation, dry granulation and direct compression. In wet granulation, components are typically mixed and granulated using a wet binder, the wet granulates are then sieved, dried and eventually ground prior to compressing the tablets. In dry granulation, powdered components are typically mixed prior to being compacted, also called pre-compression, to yield hard slugs which are then ground and sieved before the addition of other ingredients and final compression. Direct compression is now considered to be the simplest and the most economical process for producing tablets. This process requires only two steps; i.e., the mixing of all the ingredients and the compression of this mixture. A component of a tablet or capsule is usually defined as being either an excipient or an active ingredient. Active ingredients are normally ones that trigger a pharmaceutical, chemical or nutritive effect and they are present only up to the strict limit necessary for providing this effect in the right proportion. Excipients are chemically and pharmaceutically inert ingredients which are included to facilitate the preparation of the dosage forms or to adapt the release of the active ingredients. Excipients, when intended for direct compression, must fulfill a certain number of properties. They should have a high flowability. They should have a high compressibility, a good pressure-hardness profile. They should be compatible with all types of active ingredients and not interfere with their biological availability, they also should be stable against ageing, air moisture and heat. They should be colourless and tasteless. And finally they should possess proper mouthfeel. Excipients can be characterized according to their function during the formulation as, for instance, binders, disintegrants, fillers (or diluents), glidants, lubricants and eventually flavours, sweeteners and dyes. Lubricants are intended to improve the ejection of the compressed tablet from the die of the tablet-making equipment or from the punches used for compressing ingredients for introduction into capsules. Glidants are added to improve the powder flow. They are typically used to help the mixture of all the components to fill evenly and regularly the die before the compression. Fillers are inert ingredients sometimes used as bulking agents in order to decrease the concentration of the active ingredient in the final formulation. The function of filler may, in some cases, be also provided by the binder. Disintegrants may be added to formulations in order to help the tablets disintegrate ^vhen they are placed in a liquid environment and so release the active ingredient. The disintegration properties are, mostly, based upon the ability of the disintegrant to swell in the presence of a fluid, such as water or gastric juice. This swelling disrupts the continuity of the tablet structure and thus, allows the different components to enter into solution or into suspension. Commonly used disintegrants include native starches, modified starches, modified celluloses, microcrystalline cellulose or alginates. Binders are used to hold together the structure of the dosage forms. They have the property to bind together all the other ingredients after sufficient compression forces have been applied and they provide the integrity of the tablets. Commonly used compression binders include pregelatinised starches, polyvinylpyrrolidone, methylcellulose, microcrystalline cellulose, sucrose, lactose, dextrose, sorbitol or mannitol. Other cold water swellable physically modified starches are described as being useful as disintegrant but with very poor binding properties (see U.S. Pat. No. 4,383,111). In that case, the granular starch is cooked in the presence of water and possibly an organic solvent at temperature not higher than lO.degree. C. higher than its gelatinisation temperature. The so-obtained starch is then dried resulting in non-birefringent granules. Chemical modification of starch has also been investigated. Crosslinked pregelatinised starches such as starch phosphates, starch adipates, starch sulphates, starch glycolates or carboxymethyl starches are useful as disintegrants although they exhibit poor binding capacities (see U.S. Pat. No. 3,034,911 and U.S. Pat. No. 4,369,308). Dextrinised starches (see U.S. Pat. No. 4,384,005) and starch fractions such as non-granular amylose (see U.S. Pat. No. 3,490,742) are also described as having limited binding and/or disintegration properties. Though these specify the uses of various forms of starch in achieving a direct compressible form as on date there are no known direct compressible powder forms of carotenoids available. This is due to the high sensitivity of the product to various conditions such as heat, moisture, light and oxygen. The number of steps involved to generating a stable form of powder has always been difficult in particular to carotenoids. The property of limited binding of dextrinisation is overcome in this formulation. It is also known that some kinds of starch has allergenic properties. The use of maltodextrins partially circumvents as it is a modified form of starch. It now appears that there is a need for a free-flowing directly compressible powder formulation showing both an excellent compression profile and very good disintegration properties and which would aid stability to the product. Normally lubricants are added during formulation to effect smooth punching and release of tablets. During carotenoid formulation addition of lubricants facilitate carotenoid color migration. This is not recommended as this combines with other active components of the tablet and sometimes spoils the appearance of the tablet. Thus a formulation was developed having to cater to all the set conditions. According to the present invention a free-flowing directly compressible powder characterised in that it comprises regular and smooth maltodextrin powder that has an average particle size lesser than 150 fxm and a moisture content of from 3 to 5% by weight. The maltodextrin powder according to the invention is suitable for use as a binder in direct compression processes yielding very hard tablets at relatively low compression forces as well as suitable for use as a diluent and/or filler in the preparation of capsule dosage forms. The maltodextrin powder also functions as an encapsulating agent thus rendering stability to carotenoids. Tablets resulting from the compression of the maltodextrin powder disintegrate in an aqueous medium at a high speed and, additionally, exhibit a low friability pattern. The particle size of the free-flowing direct compressible powder is noticeably bigger than that of the of the carotenoid crystals (which ranges from 3 - 10 ^im) and has an average value greater than 50 .mu.m, typically from 50 to 500 .mu.m. According to the present invention there is provided a process for preparing a free-flowing direct compressible powder in a suitable blender preferably a sigma blender comprises the steps; (1) Addition of maltodextrin powder of about 150|im particle size, with a moisture content of 3.0 - 5.0% preferably 3.0%, (2) Addition of carotenoids ranging from 2 - 30% preferably mixed carotenoids containing one predominant carotenoid, (3) Addition of fine pulverized ascorbic acid powder, (4) Dry blending of the powder under vacuum or nitrogen atmosphere preferable vacuum (5) Addition of croscarmellose sodium ranging from 0.5 - 2.0% preferably 1.25% (6) Addition of expanded silica ranging from 0.5 -1.5% preferably 0.7%, (7) Dry blending under vacuum, (8) Coating of powder with ethyl cellulose dissolved in benzene free isopropyl alcohol ranging with a final dry powder concentration of 0.5 to 2.0% preferably 1.13%, (9) Drying the powder in a fluidised bed drier at 70deg C and drying is performed using nitrogen (10) Finally with vacuum drying to remove residual moisture and solvent. The maltodextrin is added to a suitable blender preferably a sigma blender with a suitable RPM to ensure that the powder should not fly during the process of blending as most of the process of blending is performed in the dry method. It is to be ensured that the maltodextin is maintained at a moisture content of 3 - 5%. Following it is the addition of mixed carotenoid crystals, which contains predominantly one carotenoid. The mixed carotenoid crystal size ranges from 0.3 ^im to lO^im. This size ensures that the crystal is well encapsulated in the maltodextrin powder. The third ingredient added is finely pulverized ascorbic acid at a concentration of 1% is added. The blender is designed to operate under vacuum. The first blending is performed under vacuum under room temperature. A fine homogenous free flowing powder is obtained. After homogenization vacuum is released using ultrapure Nitrogen. As mentioned earlier to have a tablet with suitable characteristics like disintegration and compaction other ingredients are added. Croscarmellose sodium is added in the range of 0.5 - 2.0% preferably 1.45% and expanded silica is added in the range of 0.5-1.5% preferably 0.5% are added. The blending operation is continued in the dry blending method under vacuum. After attaining the right homogeneity the next step is to coat the product. Coating is performed using ethyl cellulose. Ethyl cellulose of 1.13 grams is dissolved using 100ml of isopropyl alcohol this solution is used to coat 1000 g of the product which is dry blended. Addition of ethyl cellulose to isopropyl alcohol is done very carefully to ensure that no lumps are formed. The fine free flowing clear liquid is sprayed using a spray jet on to the powder. The fine spray is developed using ultrapure nitrogen. The isopropyl alcohol ethyl cellulose solution provides a uniform coating as a film protecting the maltodextrin from absorbing moisture and protecting carotenoids by secondary encapsulation. The volume of this solution has been standardized to ensure that the powder has uniformly coated but does not form fine lumps. The homogeneity of the powder is maintained. The powder is dried in a batch process using a fluidized bed drier in the range of 50-70 deg C. The medium used for drying the powder is hot nitrogen gas as carotenoids are easily oxidized in the presence of air. The fine dry powder contains about 5% moisture and about 0.5% isopropyl alcohol. The powder is further dried at 70 deg C under vacuum until the solvent concentration drops to 0.001% with a final moisture content of 3%. Tablets obtained using the free-flowing directly compressible powders of the present invention as binder and disintegrants are characterised by the fact that they show very high hardness at relatively low compression forces and also capable of disintegrating in an aqueous medium at a high speed, and additionally exhibit a low friability pattern. The free-flowing directly compressible powder of the invention varies in colour depending upon the percentage of carotenoids and also the kind of major carotenoid present. A free-flowing direct compressible powder may be characterized in that it comprises regular and smooth granules wherein it has an average particle size lesser than 150 ^m and a moisture content of from 3% by weight. The free-flowing compressible powders according to the present invention can be compressed into tablets with a tensile strength of at least 1 N/nmi.sup.2 when the free-flowing direct compressible powder is compressed into a tablet under a compression force of 10 kN. The directly compressible powder form shows very high stability with a retentivity of more than 97% at the end of 12 months ( Table 1). EXAMPLE This example describes the production of a free-flowing directly compressible carotenoid powder using maltodextrin. The blending operation is performed under 45% humidity as maltodextrin is hygroscopic. 13362 gms of maltodextrin containing 3% moisture with a particle size of about 150 jim is added to a sigma blender. To this mixed carotenoid crystals of 1985 gms are added. The predominant carotenoid present in the mixed carotenoid crystal is Betacarotene, which accounts to 91 % of the total mixed carotenoids. The carotenoid crystal size is predominantly maintained at 3- Sum. This ensures perfect microencapsulation by the maltodextrin. To this finely pulverized ascorbic acid of 160 gms is added giving stability to the powder. The blending process provides a homogenous free flowing carotenoid powder. The first blending operation is performed under vacuum. The second blending operation is performed after the vacuum is released using ultrapure nitrogen gas. Croscarmellose sodium at 232 gms is added to aid disintegration. Expanded silica at 80 gms is added at a percentage of 0.5% to ensure the product flowability is maintained if it is exposed to moisture conditions. The powder is again blended under vacuum and care is taken that the carotenoid powder is exposed to air as minimal as possible. After further homogenisation the coating procedure is performed with ISlgms of ethyl cellulose is dissolved in 1420 ml benzene free isopropyl alcohol. The mixture should be lump free and free flowing. Uniform coating is performed in the blender by a fine spray of the ethylcellulose mixture. The column of liquid thus standardized to obtain a product, which is just wet enough and had a uniform coating and does not form lumps. This is then as a batch process dried in a fluidized bed drier using hot nitrogen gas at 70 deg C until the moisture content is 3% and a solvent residue of 0.5 - 1.0%, The fine homogenous powder is then dried at 70deg C under vacuum to attain a free flowing homogenous powder of 2% final moisture with a solvent residue which is less than 0.001 %. The free flowing direct compressible powder may be characterized in that it comprises regular and smooth granules wherein it has an average particle size lesser than 150 jim and a moisture content of from 3% by weight. The free-flowing compressible powders according to the present invention can be compressed into tablets with a tensile strength of at least 1 N/mm.sup.2 when the free-flowing direct compressible powder is compressed into a tablet under a compression force of 10 kN. The free flowing powder can be directly filled in hard gelatin capsules. * Samples are stored in trilaminated LDPE Coated aluminum pack, packed under vacuum We claim, 1. A method of preparing free flowing direct compressible carotenoid powder for tabletting and direct hard gel filling comprising the steps of: (a) mixing ingredients in a blender comprising (1) 70 to 85% of maltodextrin in average particle size lesser than 150 [xm and a moisture content of from 3 to 5% by weight, (2) 0.1 to 1.0% of Ascorbic Acid as, (3) 2 - 30% mixed carotenoids crystal having one mixed carotenoid such that each tablet formed or hard gel capsule formed contains an effective amount of the mixed carotenoid having one predominant carotenoid , (4) 0.5 - 2.0% croscarmellose sodium, (5) 0.5 - 1.5% expanded silica gel as moisture absorbent aiding flowability, (6) 0.5 to 2.0% ethyl cellulose for stability of the mixed carotenoid crystal containing one predominant carotenoid and also as a lubricant/ glidant in tabletting/direct hard gel filling; (b) processing the product of step (a) to form a powder comprising a substantially homogeneous mixture of the components, wherein the powder is formed using a process of fluidized bed drying using hot nitrogen gas followed by vacuum drying to obtain a final moisture content of 2-3% with a solvent residue of less than 0.001%; and (c) forming tablets from the powder under a compression force of 10 kN. 2. A method as claimed in claim 1 wherein the free-flowing direct compressible powder formulation is done in a blender under vacuum to prevent degradation of carotenoids. A method as claimed in claim 1, wherein the free flowing direct compressible least 50% of the particles have a particle size of less than 150 fim. A method as claimed in claim 1 wherein the free flowing direct compressible powder prepared using maltodextrin as diluent, filler, binder and microencapsulating agent. A method as claimed in claim 1 wherein the active ingredients are mixed carotenoids containing alpha carotene, lutein, zeaxanthin, adinoxanthin with predominantly betacarotene. A method as claimed in claim 1 wherein the predominant carotenoid in the mixed carotenoid is betacarotene is 91%. A method as claimed in claim 1 wherein the dissolution agent is croscarmellose sodium. A method as claimed in claim 1, wherein the moisture absorbing agent is expanded silica. A method as claimed in claim 1 wherein the antioxidant is ascorbic acid. A method as claimed in claim 1 wherein the coating agent is ethyl cellulose. A method as claimed in claim 1, wherein the concentration of croscarmellose sodium is 1.45%. A method as claimed in claim 1, wherein the concentration of expanded silica is 0.5%. A method as claimed in claim 1 wherein the concentration of ascorbic acid is 1.0%. A method as claimed in claim 1 wherein the concentration of ethyl cellulose is 1.13%. A method as claimed in claim 1 wherein the first step of drying is performed in a fluidized bed drier using nitrogen gas at 70 deg C to attain a free flowing carotenoid powder with a moisture content of 3% and a solvent residue ranging from 0.5-L0%. A method as claimed in claim 1 wherein the powder is heated to a temperature of 70 deg +/-1.degree. C. under vacuum to attain a direct compressible carotenoid powder with a moisture content of 2% and a solvent residue less than 0.001%. A method as claimed in claim 1 wherein the particle size of the mixed carotenoid crystal carotenoids are in the range of 3 -10 fim. A method by which directly compressible carotenoid powder prepared as claimed in claim 1 is used for producing a dry compressed tablet, wherein said free-flowing directly compressible powder comprising regular, smooth, partially swollen granules of maltodextrin wherein the average particle size is about 50 .mu.m and a moisture content of from 3 to 5% by weight, said process of tablet formulation comprising directly compressing the powder under a low compression force of at least 10 kN gives a tablet having a tensile strength of at least 1 N/mm.sup.2. 19. A method for preparing a tablet as claimed in claim 19, wherein the free- flowing directly compressible process powder has an average particle size value of 100 jim. 20. A method for preparing a tablet as claimed in claim 18, wherein the free-flowing directly compressible powder has a moisture content of 3%. 21. A method as claimed in claim 1, wherein the free-flowing directly compressible powder has an particle size lesser than 150 jim. 22. A method as claimed in claim 1 wherein for preparing a free-flowing directly compressible maltodextrin carotenoid powder comprises; drying of the powder with final moisture content less than 3% with a solvent concentration below 0.001 %. 23. A free-flowing direct compressible carotenoid powder prepared using the method as claimed in claim 1, wherein compressing the said powder into a tablet form under a compression force of 10 kN to 30 kN which gives a tablet having a tensile strength of at least 1 N/mm.sup.2. 24. A method of preparing free flowing direct compressible carotenoid powder as claimed substantially herein described with foregoing description and

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