DESC:FORM 2
THE PATENTS ACT 1970
39 of 1970
&
The Patent Rules 2003
COMPLETE SPECIFICATION
(See sections 10 & rule 13)

POWDERED CURCUMIN COMPOSITION AND PREPARATION THEREOF
1. APPLICANTS (S)
(a) NAME (b) NATIONALITY (c) ADDRESS

SRI KRISHNA PHARMACEUTICALS LIMITED

INDIAN
C-4, INDUSTRIAL AREA, UPPAL, HYDERABAD – 500 039, TELANGANA, INDIA.
2. PREAMBLE TO THE DESCRIPTION

COMPLETE SPECIFICATION
The following specification particularly describes this invention and the manner in which it is to be performed

FIELD OF INVENTION:

[0001] The present invention relates to a process for preparation of water soluble powdered curcumin formulation with enhanced aqueous solubility and a determination of aqueous solubility by UV/HPLC.

BACKGROUND OF THE INVENTION

[0002] Turmeric is the dried rhizome of the plant Curcuma Longa L, which is used in food industry as colouring and flavouring agent. The dried turmeric rhizomes generally contain about 5-6% curcuminoid, which is principally responsible for its colouring ability.

[0003] Curcumin has also shown therapeutic potential against many diseases. Even today, Indians readily apply it on fresh wounds, chicken-pox scabs, and insect bites. Medical professionals prescribe it for urological diseases, worm infections, and even cancer. Such has been the hype that the yellow-golden spice is widely touted as a validation of traditional medicine. But though there have been thousands of research papers and clinical trials disclosing that curcumin has not yet resulted in the effective alternative to medicine.

[0004] Curcumin is a crystalline compound and practically insoluble in water at pH less than 7. It is a well known fact that curcumin has low solubility and bioavailability in human body as it undergoes metabolism very rapidly and results in excretion of 98% of the curcumin. The chemical properties of curcumin such as poor absorption, high first pass metabolism are few reasons that results in low solubility and bioavailability of curcumin. Enhanced low solubility and bioavailability of curcumin would take this promising natural product to the vanguard of therapeutic agents.

[0005] To improve the solubility and bioavailability of curcumin, numerous approaches have been undertaken. In a study, curcumin has been blended with the piperine to improve the bioavailability of curcumin; however it causes ulceration in stomach. Another study has shown that bioavailability of curcumin can be achieved when administered in conjunction with the black pepper extract piperine in both rats and humans, although the efficacy remains controversial. In another study, curcumin has been blended with various oils to improve the bioavailability of Curcumin; however such approach would result in curcumin not being able to be used in tableting and beverage application.

[0006] The drawbacks associated with the above techniques are as follows: 1) Solubility parameter not completely defined 2) Solubility is only defined by visual observation 3) Color is not stable over the time 4) Product is having low bulk density and tapped density 5) Product is difficulty for tableting 6) Product is hygroscopic in nature.

[0007] WO2007103435 discloses the compositions comprising curcuminoid, antioxidant, water-soluble pharmaceutically acceptable carrier and optionally an inhibitor. The said formulation with 35% w/w curcumin resulted in improved bioavailability. Solubility parameter not defined.

[0008] CN100352430C discloses self-micro-emulsified curcumin preparation comprising curcumin, surfactant, co-surfactant, oil phase and solid adsorbent providing self-micro-emulsified system having liquid drops with size below 100 nm. Such compositions show increase in curcumin solubility and absorption in gastrointestinal tract with higher bioavailability.

[0009] WO2010010431 discloses self nano-emulsion compositions comprising curcumin, a lipidic carrier system with a hydrophilic-lipophilic balance (HLB) between 3 to 14 and a pH buffer. The composition further comprises molecular aggregation inhibitor(s), a surface active agent and a co-solvent. The higher concentration of surfactants in the formulation is undesirable as they are likely to cause gastric irritation and gastric mucosal damage.

[00010] PCT/US2007/005829 describes Curcuminoid formulations having enhanced bioavailability are provided and comprise a curcuminoid, antioxidant, glucuronidation inhibitor, and water-soluble, pharmaceutically acceptable inhibitor.

[00011] PCT/KR2004/000529 describes a method for solubilization of curcumin and dispersion into water. The method prepares a water-soluble curcumin by covalent-bonding of sugar with the curcumin, thereby making the curcumin, which was insoluble in water, into a water-soluble curcumin.

[00012] Biji T Kurien et al have described yet another process to solubilize curcumin through the use of heat energy. (Improving the Solubility and Pharmacological Efficacy of Curcumin by Heat Treatment—ASSAY and Drug Development Technologies, Aug. 1, 2007, 5(4): 567-576. doi:10.1089/adt.2007.064)

[00013] Ce Cheng et al. have described a pH-driven, organic solvent-free process to improve the bioavailability of curcumin in liposomes.

[00014] The existing methods to increase the solubility and bioavailability and solubility of curcumin, such as the thin film method and the ethanol injection methods are complex and require the use of organic solvents. Since poor solubility and bioavailability of curcumin and the relatively high concentrations required for efficacy have limited its use, there is a desirability to improve the solubility and bioavailability.

OBJECTS OF THE INVENTION

[00015] An object of the invention is to provide a process for preparation of water soluble powdered curcumin.

[00016] Another object of present invention is to provide a formulation comprising water soluble powdered curcumin, wherein the concentration of curcumin is 5-10-15-20-25-30-40-50-60%.

[00017] Another object of the present invention is to provide a colouring agent comprising water soluble powdered curcumin.

[00018] Another object of the present invention is to provide a dietary supplement comprising water soluble powdered curcumin.

[00019] Another object of the present invention is to quantify the exact amount of curcumin that is dissolved in said amount of water by means of HPLC /UV.

SUMMARY OF THE INVENTION

[00020] In an aspect, the present invention provides a process for the preparation of the water soluble powdered curcumin having high solubility. The first step in the process is bringing into contact raw curcumin with at least one alkaline solution. The alkaline solution performs the function of regulating the pH of the solution at a desirable range. The second step in the process is addition of at least one polymer solution and at least one wetting agent. The polymer solution is preferably hydrophilic. The wetting agent is added to reduce the surface tension. The third step is obtaining a precipitate by regulating the pH of the solution. Maintaining the solution at an acidic pH enables precipitation of wet curcumin powder. The final step of the process is concentrating the precipitate by drying the precipitate.

[00021] In yet another aspect, the present invention provides a water soluble formulation of powdered curcumin having high solubility. The formulation according to the present invention comprises curcumin, at least one polymer selected from a group consisting of maltodextrin, cellulosic polymer, polyvinylpyrrolidone, guar gum, gum acacia, starch, hypromellose, sodium carboxymethyl cellulose, chitosan, pullulan, sucrose, glucose, dextrose or mixtures thereof. Further components of the composition include at least one wetting agent. The wetting agent is selected from a group consisting of sodium lauryl sulphate, polysorbate-20/60/80, docusate sodium, lecithin, sucrose laurate, sodium dihydrogen citrate, glyceryl monostearate, span 80 polyglycerol polyricinoleate or mixtures thereof.
[00022] The composition also comprises at least one pH regulator. The pH regulator is selected from a group consisting of citric acid, ascorbic acid, acetic acid, malic acid, hydrochoric acid, trisodium citrate or mixtures thereof. The composition also comprises at least one vitamin C derivative selected from a group consisting of ascorbyl palmitate, sodium ascorbate or mixtures thereof. The composition also comprises at least one saturated fatty acid, preferably palmitic acid, medium chain triglyceride, sunflower oil, stearic acid, linoleic acid, In addition, the composition also comprises at least one inorganic compound selected from a group consisting of sodium hydroxide, potassium hydroxide, potassium carbonate, potassium hydrogen carbonate, calcium hydroxide, trisodium orthophosphate or mixtures thereof.

[00023] The water soluble formulation of powdered curcumin thus obtained is further used in various applications, but not limited to colouring agents, dietary supplement and food products.

[00024] Further scope and applicability of the present invention will become apparent from the detailed description given hereinafter. However, it should be understood that the detailed description and specific examples, while indicating embodiments of the invention, are given by way of illustration only, because various changes and modifications within the spirit and scope of the invention will become apparent to those skilled in the art from this detailed description. It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the invention.

DETAILED DESCRIPTION

[00025] Thus, before describing the present invention in detail, it is to be understood that this invention is not limited to particularly exemplified systems or process parameters that may of course, vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments of the invention only, and is not intended to limit the scope of the invention in any manner.

[00026] The use of examples anywhere in this specification including examples of any terms discussed herein is illustrative only, and in no way limits the scope and meaning of the invention or of any exemplified term. Likewise, the invention is not limited to various embodiments given in this specification.

[00027] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. In the case of conflict, the present document, including definitions will control.

[00028] It must be noted that, as used in this specification and the appended claims, the singular forms “a” “an” and “the” include plural referents unless the content clearly dictates otherwise. Thus, for example, reference to a “polymer” may include two or more such polymers.

[00029] The terms “preferred” and “preferably” refer to embodiments of the invention that may afford certain benefits, under certain circumstances. However, other embodiments may also be preferred, under the same or other circumstances. Furthermore, the recitation of one or more preferred embodiments does not imply that other embodiments are not useful, and is not intended to exclude other embodiments from the scope of the invention.

[00030] As used herein, the terms “comprising” “including,” “having,” “containing,” “involving,” and the like are to be understood to be open-ended, i.e., to mean including but not limited to.

[00031] In order to make the matter of the invention clear and concise, the following definitions are provided for specific terms used in the following description.

[00032] The term “Curcumin” means the principal curcuminoids found in turmeric, which is a member of the ginger family (Zingiberaceae).
[00033] The term “Solubility” means amount of a substance (called the solute) that dissolves in a unit volume of a liquid substance (called the solvent preferably water) to form a saturated solution under specified conditions of temperature and pressure.

[00034] As used herein the term ‘Wetting agent’ means surface active agent or emulsifier which works by lowering the surface tension of water and enabling solubility of lipophilic compounds.

[00035] In an embodiment, the present invention provides a solvent-free process for the preparation of the water soluble powdered curcumin having high Solubility.

[00036] In another embodiment aspect, the present invention provides a process for the preparation of the water soluble powdered curcumin having high solubility. The first step in the process is bringing into contact raw curcumin with at least one alkaline solution. The alkaline solution performs the function of regulating the pH of the solution at a desirable range. The second step in the process is addition of at least one polymer solution and at least one wetting agent. The polymer solution is preferably hydrophilic. The wetting agent is added to reduce the surface tension. The third step is obtaining a precipitate by regulating the pH of the solution. Maintaining the solution at an acidic pH enables precipitation of wet curcumin powder.

[00037] In a present embodiment the efforts have been made to formulate the water soluble curcumin by using hydrophilic carrier and curcumin matrix by precipitation method.

[00038] In an embodiment the curcumin is dispersed in an alkaline solution. The alkaline solution prepared is preferably a solution of sodium hydroxide or potassium hydroxide, potassium carbonate, potassium hydrogen carbonate, calcium hydroxide, trisodium orthophosphate or mixtures thereof. In an embodiment the pH of alkaline solution is in the range of 7.5 to 12, preferably in the range of 8-12.

[00039] In an embodiment, aqueous curcumin and alkaline solution is mixed and homogenized for a period of 30-120 min. In yet another embodiment, homogenization is carried out by means of dyno-mill or colloidal mill or ball mill or Homogenization is carried out to maintain the particle size of curcumin, preferably in the range of 1-50 micron.

[00040] In yet another embodiment the particle size of curcumin should be in a range of 1-50 micron, preferably D-90 should be in the range of 5-15 micron.

[00041] The polymer solution is selected from a group consisting of ? polyvinylpyrrolidone, vinylpyrrolidone-vinyl acetate, hydroxypropyl methylcellulose, starch, sodium carboxymethyl, methyl cellulose, and other cellulosic derivative, gum acacia, guar gum, etc. Preferably the polymer solution used is a cellulosic polymer alone or combination of polysaccharides, cellulosic polymer along with vinylpyrolidone alone or its derivative. In yet another embodiment polymer solution used in the present invention is vinyl pyrolidone alone or its derivative. In yet another embodiment polymer solution used in the present invention is vinyl pyrolidone alone and its derivative along with addition of polysaccharides or cellulosic polymer or gum

[00042] The wetting agent is selected from a group consisting of sodium lauryl sulphate, polysorbate-80, polysorbate-60, docusate sodium, lecithin, polyoxyethylene glycol sorbitan alkyl esters, sorbitan alkyl esters, preferably sodium lauryl sulphate and polysorbate 80 in a range of 0.01-1%. Optionally solution of ascorbyl palmitate, sodium acrobat, medium chain triglyceride, sunflower oil, stearic acid, linoleic acid can be added.

[00043] In an embodiment, regulation of pH regulation is carried out by adding at least one acid solution. The acid solution is selected from a group consisting of dilute hydrochloric acid, acetic acid, sorbic acid, citric acid and phosphoric acid, preferably citric acid. The pH is preferably maintained in the range of about 1 to about 6.5.

[00044] In an embodiment the addition of alkaline agent along with hydrophilic polymer, weighting and buffer solution leads to gelling of the products and thus results in precipitation of matrix.

[00045] In an embodiment, the precipitate is obtained by filtration of solution. The filtration is preferably carried out using nutch filter under vacuum.

[00046] The process of concentration of precipitate is carried out by drying the precipitate, preferably in a tray dryer and milled preferably in a multimill.

[00047] In an embodiment, filtrate from aforesaid filtration is heated to obtain precipitate which is further dried to obtain the powdered curcumin of present invention.

[00048] The heating is carried in a predefined temperature and duration. The temperature of heating is preferably in the range of about 80oC to about 100°C, preferably 90°C. The duration of heating is preferably in the range of 3-8 hours, preferably 3-4.

[00049] The final formulation should be in the form of solid granules. As per saturated solubility product is 2-8mg/ml. Final product should be easy for tableting and capsule filling with high bulk density of 0.5-0.6 and tapped density of 0.7-0.8

[00050] In yet another aspect, the present invention provides a water soluble formulation of powdered curcumin having high solubility. The formulation according to the present invention comprises Curcumin, at least one polymer selected from a group consisting of maltodextrin, cellulosic polymer, polyvinylpyrrolidone, guar gum, gum acacia, starch, hypromellose, sodium carboxymethyl cellulose, chitosan, pullulan or mixtures thereof. Further components of the composition include at least one wetting agent. The wetting agent is selected from a group consisting of sodium lauryl sulphate, polysorbate-20/60/80, docusate sodium, lecithin, sucrose laurate, sodium dihydrogen citrate, glyceryl monostearate, span 80 polyglycerol polyricinoleate or mixtures thereof.

[00051] The composition also comprises at least one pH regulator. The pH regulator is selected from a group consisting of citric acid, ascorbic acid, acetic acid, malic acid, hydrochloric acid, trisodium citrate or mixtures thereof. The composition also comprises at least one vitamin C derivative selected from a group consisting of ascorbyl palmitate, sodium ascorbate or mixtures thereof. The composition also comprises at least one saturated fatty acid, preferably palmitic acid medium chain triglyceride, sunflower oil, stearic acid, linoleic acid, corn oil. In addition, the composition also comprises at least one inorganic compound selected from a group consisting of sodium hydroxide, potassium hydroxide, potassium carbonate, potassium hydrogen carbonate, calcium hydroxide, trisodium orthophosphate or mixtures thereof.

[00052] In an embodiment, the amount of curcumin in the composition is in range of 0.1-60 wt%, the amount polymer is in the range of 0.1-90 wt%, the amount of wetting agent is in the range of 0.1-10wt%, the amount of pH regulator is in the range of 0.1-20 wt%, the amount of saturated fatty acid is in the range of 1-10 wt%, the amount of inorganic compound is in the range of 1-20wt%.

[00053] The water soluble formulation of powdered curcumin thus obtained is further used in various applications, but not limited to colouring agents, dietary supplement.

[00054] The compositions of the present invention are water soluble. The compositions prepared by using the water soluble powder curcumin as per the above process has shown marked increase in the solubility curcumin.

[00055] The compositions of the present invention are physiologically stable and directly compressible to a non-hygroscopic powder form for easy handling and formulation in tablet and capsule forms.

[00056] In yet another embodiment a method based on HPLC (High Performance Liquid Chromatography) and UV has been developed to determine the exact amount of solute dissolved in exact amount of solvent.

DETERMINATION OF SOLUBILITY BY USING UV / HPLC

[00057] The water soluble powdered curcumin is analyzed by using HPLC (Assay) against USP standards. Saturated solubility of water soluble powdered curcumin was carried out at room temperature along with raw Curcuminoids -95%. Both the solution was filter and clear solution was tested at UV and HPLC.

[00058] Solubility determination of Curcumin water soluble powder by using ultra-violet spectroscopy.

[00059] The solubility of water soluble powdered curcumin is characterized by ultra-violet radiation using the following procedure:

PREPARATION OF SOLUTIONS
PREPARATION OF 1MG/ML SOLUTION OF CITRIC ACID

[00060] Weigh and transfer accurately about 1g of citric acid into 1000 ml volumetric flask add about 500 ml HPLC grade Water sonicate to dissolve at room temperature, dilute to volume with HPLC grade Water.

PREPARATION OF DILUENT:

[00061] Tetrahydrofuran and 1mg/ml solution of citric acid in water in the ratio of 40:60% v/v

PREPARATION OF 40 PPM STANDARD SOLUTION OF CURCUMINOIDS-95%

[00062] Weigh and transfer accurately about 20 mg of Curcuminoids-95% into 50 ml volumetric flask and add about 30 ml of diluent, and sonicate to dissolve and make up to the mark diluent, and mix well.

[00063] Dilute 5 ml of above solution to 50 ml with diluent.

PREPARATION OF 4 PPM STANDARD SOLUTION OF CURCUMINOIDS-95%

[00064] Dilute 5 ml of above standard solution to 50 ml with diluent and mix well.

PREPARATION OF SATURATED SOLUTION OF CURCUMINOIDS-95% IN HPLC GRADE WATER

[00065] Weigh and transfer accurately about 1g of Curcuminoids-95% into 100 ml of HPLC grade Water and sonicate to dissolve for one hour and allow the solution to settle down for half an hour and centrifuge the solution at 5000 rpm for 5 minutes and collect the supernatant to centrifuge tube and centrifuge again at 5000 rpm for 5 minutes and filter the solution through 0.45µm Nylon filter.

PREPARATION OF SATURATED SOLUTION CURCUMIN WATER SOLUBLE POWDER -20% IN HPLC GRADE WATER: (IN DUPLICATE)

[00066] Weigh and transfer accurately about 5g of (5g powder contain 1g of curcuminoids) Curcumin water soluble powder -20% of present invention into 100 ml of HPLC grade Water and sonicate to dissolve for one hour and allow the solution to settle for half an hour, and centrifuge the solution at 5000 rpm for 5 minutes and collect the supernatant to centrifuge tube and centrifuge again at 5000 rpm for 5 minutes and filter the solution through 0.45µm Nylon filter.

PREPARATION OF SAMPLE SOLUTION (CURCUMIN WATER SOLUBLE POWDER -20%)

[00067] Dilute 1 ml of saturated solution of sample into 100 ml volumetric flask and make up the volume with HPLC grade Water up to the mark. Further diluted 4 ml of above solution to 100 ml with HPLC grade Water in 100 ml volumetric flask.

PROCEDURE FOR ANALYSIS OF CURCUMIN WATER SOLUBLE POWDER BY USING ULTRA VIOLET SPECTROSCOPY (UV)

[00068] Record the absorbance of 4 PPM standard solution (Curcuminoids -95%) using diluent (Tetrahydrofuran and 1mg/ml solution of citric acid in water in the ratio of 40:60% v/v) as blank and saturated solution of standard (Curcuminoids -95%) and sample solution (Curcumin water soluble powder ) in water using water as blank at 420 nm photometrically.

CALCULATION:

Saturated Sample Solution Concentration
=

Saturated Standard Solution Concentration =

SOLUBILITY DETERMINATION OF CURCUMIN WATER SOLUBLE POWDER BY HIGH PERFORMANCE LIQUID CHROMATOGRAPHY

[00069] The solubility of water soluble powdered curcumin of present invention is characterized by high performance liquid chromatography using the following procedure:

PREPARATION OF SOLUTIONS:
PREPARATION OF 1MG/ML SOLUTION OF CITRIC ACID:

[00070] Weigh and transfer accurately about 1g of citric acid into 1000 ml volumetric flask add about 500 ml HPLC grade Water sonicate to dissolve at room temperature, dilute to volume with HPLC grade Water.

PREPARATION OF DILUENT:

[00071] Tetrahydrofuran and 1mg/ml solution of citric acid in water in the ratio of 40:60% v/v

PREPARATION OF 40 PPM STANDARD SOLUTION

[00072] Weigh and transfer accurately about 20 mg of Curcuminoids-95% into 50 ml volumetric flask and add about 30 ml of diluent and sonicate to dissolve and make up to the mark with diluent and mix well. Dilute 5 ml of above solution to 50 ml with diluent.

PREPARATION OF SATURATED SOLUTION OF CURCUMINOIDS-95% IN HPLC GRADE WATER

[00073] Weigh and transfer accurately about 1g of Curcuminoids-95% into 100 ml of HPLC grade Water and sonicate to dissolve for one hour and allow the solution to settle down for half an hour and centrifuge the solution at 5000 rpm for 5 minutes and collect the supernatant to centrifuge tube and centrifuge again at 5000 rpm for 5 minutes and filter the solution through 0.45µm Nylon filter.

PREPARATION OF SATURATED SOLUTION OF CURCUMIN WATER SOLUBLE POWDER IN HPLC GRADE WATER (IN DUPLICATE)

[00074] Weigh and transfer accurately about 5g of (5g powder contain 1g of curcuminoids) Curcumin water soluble powder -20% into 100 ml of HPLC grade Water and sonicate to dissolve for one hour and allow the solution to settle for half an hour, and centrifuge the solution at 5000 rpm for 5 minutes and collect the supernatant to centrifuge tube and centrifuge again at 5000 rpm for 5 minutes and filter the solution through 0.45µm Nylon filter.

PREPARATION OF SAMPLE SOLUTION:

[00075] Dilute 1 ml of saturated solution of sample into 100 ml volumetric flask and make up the volume with HPLC grade water upto the mark. Further diluted 4 ml of above solution to 100 ml with HPLC grade Water in 100 ml volumetric flask.

PROCEDURE FOR CHARACTERIZATION OF CURCUMIN WATER SOLUBLE POWDERED BY USING HPLC

[00076] Inject the diluent as a blank, 40 PPM (Curcuminoids -95%) Standard solution, Saturated solution of Standard (Curcuminoids -95%) in HPLC grade water, Saturated solution of (Curcumin water soluble powder sample) in HPLC grade Water in HPLC and record the area at 420nm.

CALCULATION:

Saturated Sample Solution concentration =

Saturated Standard Solution concentration =

[00077] The following exemplary embodiment will serve to illustrate the practice of this invention, it being understood that the particulars shown are by way of example and for purpose of illustrative discussion of non-limiting preferred embodiments of the invention.

EXEMPLARY FORMULATION: 1
[00078] Curcumin 240 g, Polyvinylpyrrolidone 250 g, Starch 250 g, Sodium hydroxide 10 g, Sodium Lauryl Sulphate 5 g, Medium chain triglycerides 50 g, Hydroxypropyl methylcellulose 185 g, citric Acid 10g

EXEMPLARY FORMULATION: 2
[00079] Curcumin 240g, Polyvinylpyrrolidone 150g, Maltodextrin 400g, Sodium hydroxide 20g, Polysorbate -80 20 g, Sunflower Oil 50g, Hydroxypropyl methylcellulose 100g, Citric Acid 20g

EXEMPLARY FORMULATION: 3
[00080] Curcumin 240g, Maltodextrin 400g, Sucrose 150g, Potassium Hydroxide 20g, Medium chain triglycerides 20g, Hydroxypropyl methylcellulose 168g Citric Acid 2g

EXEMPLARY FORMULATION: 4
[00081] Curcumin 240g Maltodextrin 494 g, Sucrose 160g Sodium hydroxide 20g, Medium chain triglycerides 8g, Gum Acacia 74g, Citric Acid 4g

EXEMPLARY FORMULATION: 5
[00082] Curcumin 450g Maltodextrin 250g Sucrose 250 g, Potassium Hydroxide 4g, Sunflower oil 8g, Gum Acacia 37g, Citric Acid 1g.

EXEMPLARY FORMULATION: 6
[00083] Curcumin 240g, Sodium carboxymethyl cellulose 500g Sucrose 50g , Potassium Hydroxide 40 g, Sunflower Oil 80g , Gum Acacia 85 g, Citric Acid 5g.

EXEMPLARY FORMULATION: 7
[00084] Curcumin 240g, Sodium carboxymethyl cellulose 400g Sucrose 50g , Potassium Hydroxide 40 g, Sunflower Oil 80g , Gum Acacia 188 g, Citric Acid 2g

EXEMPLARY FORMULATION: 8
[00085] Curcumin 240g, Sodium carboxymethyl cellulose 600g Sucrose 50g , Potassium Hydroxide 25 g, Sunflower Oil 8g , Gum Acacia 62 g, Citric Acid 15g

EXEMPLARY FORMULATION: 9
[00086] Curcumin 240g, Maltodextrin 500g Sucrose 50g , Potassium Hydroxide 40 g, Sunflower Oil 80 g , Gum Acacia 86 g, Citric Acid 4g

EXEMPLARY FORMULATION: 10

[00087] Curcumin 240g, Polyvinylpyrrolidone 450g, Sucrose 50 g, Sodium Hydroxide 40g , Sunflower Oil 80g, Sodium Lauryl Sulphate 10g, Gum Acacia124 g, Citric Acid 6g.

TEST FOR STABILITY
[00088] The stability of the powdered curcumin composition of the present invention was investigated by storing the powdered curcumin (20%) of the invention at a temperature of 40±2oC at a relative humidity 75±5 %. The stability of the curcumin was observed at an interval of one month for a period of six months. From the data it is observed that, no degradation was observed in 6 months for the three batches as shown below.

Storage Condition: 40 ± 2°C / 75 ± 5% RH

Time Interval Description Assay (%) LOD (%) Remarks
Initial Yellowish Brown free flowing Crystalline Powder 22.31 1.69 PASS
One month Yellowish Brown free flowing Crystalline Powder 23.01 4.10 PASS
Two months Yellowish Brown free flowing Crystalline Powder 22.04 3.94 PASS
Three Months Yellowish Brown free flowing Crystalline Powder 22.39 4.03 PASS
Six months
Yellowish Brown free flowing Crystalline Powder 22.83 3.78 PASS
BATCH 1
Storage Condition: 40 ± 2°C / 75 ± 5% RH
Time Interval Description Assay (%) LOD (%) Remarks
Initial Yellowish Brown free flowing Crystalline Powder 21.06 6.87 PASS
One month Yellowish Brown free flowing Crystalline Powder 22.38 2.43 PASS
Two months Yellowish Brown free flowing Crystalline Powder 22.86 2.42 PASS
Three months Yellowish Brown free flowing Crystalline Powder 21.31 2.45 PASS
Six months
Yellowish Brown free flowing Crystalline Powder 22.69 2.19 PASS

BATCH 2

BATCH 3

Storage Condition: 40 ± 2°C / 75 ± 5% RH
Time Interval Description Assay (%) LOD (%) Remarks
Initial Yellowish Brown free flowing Crystalline Powder 21.21 2.28 PASS
One month Yellowish Brown free flowing Crystalline Powder 22.10 2.24 PASS
Two months Yellowish Brown free flowing Crystalline Powder 22.76 2.24 PASS
Three months Yellowish Brown free flowing Crystalline Powder 22.24 2.23 PASS
Six months Yellowish Brown free flowing Crystalline Powder 21.98 2.24 PASS
STABILITY OF COLOR IN WATER

[00089] Aqueous color stability of water soluble powdered curcumin in water was tested.

SAMPLE 1
[00090] 100 mg of Curcuminoids -95% was added to 100 ml of HPLC water and mixed well.

SAMPLE 2
[00091] 500 mg of Curcumin water soluble powder -20% (500 mg of formulation is equivalent to 100mg of curcuminoids -95%) was added to 100 ml of HPLC water and mixed well. Both the samples were kept at room temperature and periodically checked every 1 hour.

CONCLUSION
It was observed that the color strength of Curcumin Water Soluble powder solution was stable for 1 month ,Physical observation.
,CLAIMS:We Claim:

1) A water soluble curcumin composition comprising:
curcumin;
at least one polymer;
at least one wetting agent;
at least one pH regulator;
at least one vitamin C derivative;
at least one saturated fatty acid; and
at least one inorganic compound.

2) The composition as claimed in claim 1, wherein the amount of curcumin is in the range of 0.1-60 wt%, the amount polymer is in the range of 0.1-90 wt%, the amount of wetting agent is in the range of 0.1-10 wt%, the amount of pH regulator is in the range of 0.1-20 wt%, the amount of vitamin C derivative is 2-20 % wt%, the amount of saturated fatty acid is in the range of 1-10wt%, the amount of inorganic compound is in the range of 1-20 wt%.

3) The composition as claimed in claim 1, wherein said at least one polymer is selected from a group consisting of maltodextrin, cellulosic polymer, polyvinylpyrrolidone, guar gum, gum acacia, starch, hypromellose, sodium carboxymethyl cellulose, chitosan, pullulan, Sucrose, Glucose, dextrose or mixtures thereof.

4) The composition as claimed in claim 1, wherein said at least one wetting agent is selected from a group consisting of sodium lauryl sulphate, polysorbate-20/60/80, docusate sodium, lecithin, sucrose laurate, sodium dihydrogen citrate, glyceryl monostearate, span 80 polyglycerol polyricinoleate or mixtures thereof.

5) The composition as claimed in claim 1, wherein said at least one pH regulator is selected from a group consisting of citric acid, ascorbic acid, acetic acid, malic acid, hydrochoric acid, trisodium citrate or mixtures thereof.

6) The composition as claimed in claim 1, wherein said at least one vitamin C derivative is selected from a group consisting of ascorbyl palmitate, sodium ascorbate or mixtures thereof.

7) The composition as claimed in claim 1, wherein said at least one saturated fatty acid is selected from a group comprising of palmitic acid, medium chain triglyceride, sunflower oil, stearic acid, linoleic acid.

8) The composition as claimed in claim 1, wherein said at least one inorganic compound is selected from a group consisting of sodium hydroxide, potassium hydroxide, potassium carbonate, potassium hydrogen carbonate, calcium hydroxide, trisodium orthophosphate or mixtures thereof.

9) A process for preparation of water soluble curcumin composition comprising the steps of
(a) contacting raw curcumin with at least one alkaline solution;
(b) adding at least one polymer solution and at least one wetting agent to solution of step (a);
(c) obtaining a precipitate by maintaining the solution of step (b) at a pH the range of 7.5 to 12, preferably in the range of 8-12; and
(d) concentrating and drying the precipitate from step (c).

Nalini Kant Pandey
Bizrights IP Partners LLP
(IN/PA 2187)
Agent for applicant(s)
Date: 07.06.2019