Novel curcumin NANO-formulation and process for preparation thereof

Abstract

The present invention provides nano-formulation of Curcumin having nano Curcumin content up to 10% w / w in formulation (up to 90 mg) with 100% solubility in water, - and particle size less than 100 nm with good bioavailability through enhanced permeability and stability, thereby increase in their effectiveness for various therapeutic uses. The nano-formulation of Curcumin is having low particle size and increased efficacy, stability against pH, light, temperature, and humidity.

Description

[0001] NOVEL CURCUMIN NANO-FORMULATION AND PROCESS FOR

[0002] PREPARATION THEREOF

[0003] FIELD OF THE INVENTION:

[0004] The invention provides a nano-formulation of Curcumin having particle size less than 100 nm with good bioavailability and 100% solubility in water and enhanced permeability, thereby increase in their effectiveness for various therapeutics uses.

[0005] BACKGROUND OF THE INVENTION:

[0006] The following background discussion includes information that may be useful in understanding the present invention. It is not an admission that any of the information provided herein is prior art or relevant to the presently claimed invention, or that any publication specifically or implicitly referenced is prior art.

[0007] Curcumin are active components obtained from the rhizomes of Curcuma longa L., from family Zingiberaceae (Turmeric). In C. longa roots; Curcumin content varies from 1 to 6% or more, depending on its origin.

[0008] Curcumin is indeed a fascinating compound, known for its vibrant yellow-orange color and its presence in turmeric, a spice commonly used in cooking and traditional medicine. Its chemical formula is C21H20O6 and molecular weight is 368.39 g / mol. The melting temperature of Curcumin, 183°C, indicates the temperature at which it transitions from a solid to a liquid state.

[0009] It exists in two forms viz. keto and enol form. In neutral and acidic solutions, the keto form is predominant. However, in the solid state and in alkaline solutions, stable enol form becomes predominant.

[0010] Curcuminoids are polyphenols containing three main components: Curcumin (77%), desmethoxycurcumin (17%) and bis-demethoxycurcumin (3%), among them, the most biologically active ingredient is Curcumin.

[0011] Curcumin's role in managing chronic diseases is indeed significant, and its effects are mediated through the modulation of various signal transduction pathways, particularly those involving key inflammatory biomarkers such as tumor necrosis factor-alpha (TNF-a), tumor necrosis factor-beta (TNF-P), and interleukins (IL) like IL-1, IL-2, IL-8, and IL- 12. Several studies have demonstrated Curcumin's ability to modulate TNF-a and other pro- inflammatory cytokines. For example, in the context of multiple myeloma cells, Curcumin has been shown to inhibit IL-6-induced STAT3 phosphorylation and subsequent nuclear translocation, thereby affecting cell signalling pathways involved in inflammation.

[0012] Moreover, Curcumin targets pathways such as the nuclear factor kappa-light-chain enhancer of activated B cells (NF-KB) and mitogen- activated protein kinases (MAPK), which are crucial in regulating the expression of inflammatory cytokines (such as TNF-a). By interfering with these pathways, Curcumin can prevent the production of inflammatory cytokines like IL-1 and IL-6 induced by TNF-a.

[0013] Curcumin has attracted particular attentions in recent years due to its broad spectrum of beneficial biological and pharmacological activities, such as anti-inflammatory, anti-oxidant, anti-microbial, anti-tumor, anti-coagulant, anti-virus properties. Moreover, Curcumin has been shown to have the potential of slowing the progress of Alzheimer’s disease.

[0014] Despite having various health functionalities, the major issue with Curcumin is its hydrophobic nature with a logP value of ~3.0. Due to its hydrophobic nature, it is poorly soluble in water, which results in very low permeability and bioavailability. Curcumin has poor water solubility (0.0004 mg / ml), low oral bioavailability, chemical instability, and prone to photolysis. Furthermore, it has low membrane permeability and has difficulties in optimum metabolism and excretion. Instability at alkaline pH and short half-life lead to low oral bioavailability and limits the therapeutic applications.

[0015] In order to overcome these limitations, numerous methods have been suggested / tried to improve the Curcumin bioavailability. However, there is still a gap in delivery of Curcumin for its uses in various indications mentioned above.

[0016] The present invention provides Novel Curcumin Nano-Formulation having high Curcumin content in nano form, increased bioavailability, 100% solubility, permeability, photo- stability and longer shelf life compared to commercial Curcumin and commercially available nano Curcumin formulations.

[0017] OBJECTIVE OF THE INVENTION:

[0018] The primary object of the present invention is to overcome the drawback associated with prior art. Another object of the present invention is to provide nano-formulation of Curcumin having particle size less than 100 nm with good bioavailability and 100 % water solubility thus enhanced permeability, thereby increase in their effectiveness for various therapeutics uses.

[0019] Another object of the present invention is to provide nano-formulation of Curcumin having low particle size and increased efficacy, stability against pH, light, temperature, and humidity.

[0020] Another object of the present invention is to provide nano -formulation of Curcumin which has concentration of 50mg to 90mg or more, high permeability, improved stability, photo -stability and efficacy.

[0021] Another object of the present invention is to provide a method of preparing a nano-formulation of Curcumin which has concentration of 50mg to 90mg or more, high permeability, improved stability, photo- stability and efficacy.

[0022] SUMMARY OF THE INVENTION:

[0023] In an aspect the present invention provides a Curcumin nano-formulation with enhanced efficacy and bioavailability, comprising: a) Diethylene glycol mono ethyl ether in a weight ranging from 140 to 160 mg; b) Medium-Chain Triglycerides in a weight of 90 to 110 mg; c) PEG-40 Hydrogenated Castor Oil in a weight of 90 to 110 mg; d) Polyoxyl 35 Castor Oil in a weight of 140 to 160 mg; e) Lauroyl Polyoxyl-32 glycerides and PEG 6000 in a weight of 90 to 110 mg; f) PEG-32 sterate in a weight of 140 to 160 mg; g) polyoxyethylene sorbitan monooleate in a weight of 40 to 60 mg; h) mixture of propylene glycol caprylate and refined soybean oil, glyceryl distearate (C18) and polyglyceryl -3 dioleate (cl8:l) present in a weight of 40 to 60 mg; and i) Curcumin in the amount / s of 50mg, 70mg and 90 mg.

[0024] In an aspect the present invention provides a Curcumin nano-formulation with enhanced efficacy and bioavailability, comprising a) Diethylene glycol mono ethyl ether in a weight of 150 mg; b) Medium-Chain Triglycerides in a weight of 100 mg; c) PEG-40 Hydrogenated Castor Oil in a weight of 100 mg; d) Polyoxyl 35 Castor Oil in a weight of 150mg; e) Lauroyl Polyoxyl-32 glycerides and PEG 6000 in a weight of lOOmg; f) PEG-32 sterate in a weight of 150 mg; g) polyoxyethylene sorbitan monooleate in a weight of 50 mg; h) mixture of propylene glycol caprylate and refined soybean oil, glyceryl distearate (C18) and polyglyceryl -3 dioleate (cl8:l) present in a weight of 50 mg; and i) curcumin in the amount / s of 50mg, 70mg and 90 mg.

[0025] DETAILED DESCRIPTION OF DRAWINGS:

[0026] To further clarify advantages and features of the present invention, a more particular description of the invention will be rendered by reference to specific embodiments thereof, which is illustrated in the appended drawings. It is appreciated that these drawings depict only typical embodiments of the invention and are therefore not to be considered limiting of their scope. The invention will be described and explained with additional specificity and detail with the accompanying drawings in which:

[0027] Fig. 1: Illustrate the particle size of NCNF A variants.

[0028] Fig. 2: Illustrate the particle size of NCNF B variants.

[0029] Fig. 3: Illustrate the particle size of NCNF C variants.

[0030] Fig. 4: Illustrate the graph of permeability study NCNF variants and commercially available Curcumin.

[0031] Fig. 5: Illustrate the particle size of NCNF variants for the stability studies.

[0032] Fig. 6: Illustrate the average particle size of NCNF size before and after Stability studies.

[0033] DETAILED DESCRIPTION:

[0034] For the purpose of promoting an understanding of the principles of the invention, reference will now be made to the embodiment illustrated in the drawings and specific language will be used to describe the same. It will nevertheless be understood that no limitation of the scope of the invention is thereby intended, such alterations and further modifications in the illustrated system, and such further applications of the principles of the invention as illustrated therein being contemplated as would normally occur to one skilled in the art to which the invention relates. It will be understood by those skilled in the art that the foregoing general description and the following detailed description are exemplary and explanatory of the invention and are not intended to be restrictive thereof.

[0035] In an embodiment, the present invention provides nano-formulation of Curcumin having particle size less than 100 nm with good bioavailability and 100% water solubility, thus enhanced permeability, thereby increase in their effectiveness for various therapeutic uses. The developed NCNF is having low particle size and increased efficacy, stability against pH, light, temperature and humidity.

[0036] In an embodiment, the present invention nano-formulation of curcumin uses different type of GRAS Solubilizers / Surfactants like, Diethylene glycol mono ethyl ether, Polyoxyl 15- hydroxystearate, Medium-Chain Triglycerides, PEG-40 Hydrogenated Castor Oil, Polyoxyl 35 Castor Oil, Lauroyl Polyoxyl-32 glycerides and PEG 6000, PEG-32 sterate, polyoxyethylene sorbitan monooleate, propylene glycol caprylate, Propylene Glycol Mono and Di Caprylate, Mixture of refined soybean oil, glyceryl distearate (C18) and polyglyceryl -3 dioleate (cl8: 1).

[0037] In an embodiment, the present invention nano -formulation has various combination of formulations in different combinations were prepared and analysed for their solubility, stability, non-precipitation, particle size etc. and finally nine combinations containing three different concentrations of Curcumin were finalized and evaluated.

[0038] Table-1: NCNF Composition

[0039] Three different combinations were made (NCNF A, NCNF B and NCNF C) using different concentrations of Curcumin (50, 70 and 90 mg).

[0040] In total nine, Self-nano-emulsifying drug delivery system (SNEDDS) formulations were prepared.

[0041] In an embodiment, in the present invention, preparation of novel Curcumin composition using innovative process has following steps for NCNF A Variants (Curcumin 50 mg, 70 mg and 90 mg):

[0042] 1. Accurately weighed the quantities of ingredients of no. 1-4 and 5-8 taken separately in vessel A and vessel B respectively. The mixture 1-4 in vessel A was heated under stirring condition for 5-10 minutes at 65-70°C, while vessel B was kept on mild heating (45-55 C)

[0043] 2. In vessel A with mixture 1-4, accurately weighed quantity of Curcumin 50 mg was added to form homogenous mixture using high speed homogenizer for 7-8 min at 7,000 - 8,000 rpm, at 40-45°C.

[0044] 3. Preheated (45-55 C) mixture of 5-8 from vessel B were added into the above homogenized solution and further sonicated for 25-30 minutes at 40-45°C. Further homogenization was carried out for 7-8 min at 7,000 - 8,000 rpm. This prepared formulation was labelled as NCNF A-50.

[0045] 4. Similar methodology was used for the preparation for NCNF A-70 (Curcumin 70 mg) and NCNF A-90 (Curcumin 90 mg) formulations.

[0046] Table-2: Composition for NCNF A-50 Table-3: Composition for NCNF A-70

[0047] Table-4: Composition for NCNF A-90

[0048] The Invention in its preferred embodiment provides the nano-formulation of curcumin, referred as NCNF B Variant (Curcumin 50 mg, 70 mg and 90 mg).

[0049] In an embodiment, NCNF B Variant is prepared through following steps:

[0050] 1. Accurately weighed the quantities of ingredients of no. 1-5 mentioned in Table -1 (i.e. Diethylene glycol mono ethyl ether, Medium-Chain Triglycerides, PEG-40 Hydrogenated Castor Oil, Polyoxyl 35 Castor Oil, Lauroyl Polyoxyl-32 glycerides and PEG 6000) and 6-9 (i.e. PEG-32 sterate, Polyoxyethylene sorbitan monooleate, Propylene glycol caprylate; mixture of refined soybean oil, glyceryl distearate (Cl 8) and polyglyceryl -3 dioleate (cl8: 1)) taken separately in vessel A and vessel B. The mixture 1-5 in vessel A was heated under stirring condition for 10-15 minutes at 60- 75°C, while vessel B was kept on mild heating (45-55 C)

[0051] 2. In vessel A with mixture 1-5, accurately weighed quantity of Curcumin 50 mg was added to form homogenous mixture using high speed homogenizer for 10-15 min at 8,000 - 10,000 rpm, at 40-50°C.

[0052] 3. Preheated (45-55 C) mixture of 6-9 from vessel B were added into the above homogenized solution and further sonicated for 30-35 minutes at 45-55°C. Further homogenization was carried out for 10-15 min at 8,000 - 10,000 rpm. This prepared formulation was labelled as NCNF B-50.

[0053] 4. Similar methodology was used for the preparation for NCNF B-70 (Curcumin 70 mg) and NCNF B-90 (Curcumin 90 mg) formulations.

[0054] In an embodiment, the composition for NCNF B comprises following components: a) Diethylene glycol mono ethyl ether in a weight of 150 mg; b) Medium-Chain Triglycerides in a weight of 100 mg; c) PEG-40 Hydrogenated Castor Oil in a weight of 100 mg; d) Polyoxyl 35 Castor Oil in a weight of 150mg; e) Lauroyl Polyoxyl-32 glycerides and PEG 6000 in a weight of lOOmg; f) PEG-32 sterate in a weight of 150 mg; g) polyoxyethylene sorbitan monooleate in a weight of 50 mg; h) mixture of propylene glycol caprylate and refined soybean oil, glyceryl distearate

[0055] (C18) and polyglyceryl -3 dioleate (cl8:l) present in a weight of 50 mg; and i) Curcumin in the amount / s of 50mg, 70mg and 90 mg.

[0056] In a preferred embodiment, the composition for NCNF B comprises following components:

[0057] Table-5: Composition for NCNF B-50

[0058] Table-6: Composition for NCNF B-70

[0059] Table-7: Composition for NCNF B-90

[0060] NCNF C Variants (Curcumin 50 mg, 70 mg and 90 mg):

[0061] 1. Accurately weighed the quantities of ingredients of no. 1-3 and 4-7 taken separately in vessel A and vessel B. The mixture 1-3 in vessel A was heated under stirring condition for 5-10 minutes at 55-65°C, while vessel B was kept on mild heating (40-50°C)

[0062] 2. In vessel A with mixture 1-3, accurately weighed quantity of Curcumin 50 mg was added to form homogenous mixture using high speed homogenizer for 5-10 min at 6,000 - 8,000 rpm, at 45-55°C.

[0063] 3. Preheated (40-50°C) mixture of 4-7 from vessel B were added into the above homogenized solution and further sonicated for 20-30 minutes at 40-55°C. Further homogenization was carried out for 5-10 min at 6,000 - 8,000 rpm. This prepared formulation was labelled as NCNF C-50.

[0064] 4. Similar methodology was used for the preparation for NCNF C-70 (Curcumin 70 mg) and NCNF C-90 (Curcumin 90 mg) formulations. Table-8: Composition for NCNF C-50

[0065] Table-9: Composition for NCNF C-70

[0066] Table-10: Composition for NCNF C-90

[0067] REDUCTION IN PARTICLE SIZE FOR IMPROVED EFFICACY:

[0068] NCNF formulations were analysed for particle size using Particle size analyser.

[0069] Table 11: Average Particle Size in nm for different NCNF formulations

[0070] Based on the uniformity of particle size, 4 formulations having average particle size less than 100 nm were selected, NCNF A-50, NCNF B-50, NCNF B-70 and NCNF B-90 were further evaluated for various parameters.

[0071] COMPARATIVE IMPROVEMENT IN PERMEABILITY:

[0072] Permeability studies were performed using Everted Gut Sac method. Ileum was cut into 10-12 cm long pieces and gently everted. Gut Sac were prepared and filled with 5 ml of ringer solution. Prepared Gut Sacs were placed in separate beakers containing 50 ml of 1000 ppm NCNF formulations along with commercially available Curcumin and nano-Curcumin under constant agitation and aeration at 35-37°C for 90 min.

[0073] After 90 minutes gut sacs were removed and outer surface was washed thoroughly. Sacs were opened and ringer solution was collected in pre-labelled tubes. Curcumin quantification was carried out using HPLC analysis.

[0074] Table-12: Permeability: Number of Fold Increase

[0075] The increase in permeability was compared with commercially available nano formulation.

[0076] COMPARATIVE IMPROVEMENT IN ANTIOXIDANT POTENTIAL:

[0077] The three formulations having permeability better than commercial sample and Curcumin were evaluated for their anti-oxidant activity using DPPH method to calculate IC-50 value and % inhibition, observations are as follows:

[0078] Table-13: NCNF Anti-Oxidant IC50 activity

[0079] Table-14: NCNF Anti-Oxidant % inhibition activity

[0080] Anti-Oxidant IC50 concentrations were lower and % inhibition was higher in NCNF formulations compared to commercially available Curcumin and nano Curcumin.

[0081] COMPARATIVE IMPROVEMENT IN ANTI-INFLAMMATORY ACTIVITY:

[0082] The three formulations having better permeability and anti-oxidant activity were evaluated for their anti-inflammatory activity using Protein denaturation method to calculate IC-50 value and % inhibition, observations are as follows:

[0083] Table-15: NCNF Anti-inflammatory IC 50 activity

[0084] Table-16: NCNF Anti-inflammatory % inhibition activity

[0085] Anti-Inflammatory IC50 concentrations were lower and % inhibition was higher in NCNF formulations compared to commercially available Curcumin and nano Curcumin.

[0086] PHOTO-STABILITY ENHANCEMENT:

[0087] Curcumin is quite photo labile and degrades rapidly, especially in the presence of UV light, hence in order to evaluate the Photo- stability of the NCNF formulations along with commercial nano Curcumin experiments were carried out. The developed formulations were kept in Transparent and Amber colour containers and stored at room temperature, with and without UV treatments.

[0088] After completion of treatment, samples of all the formulations were analysed for their photostability at initial, 90 minutes and 360 minutes (Transparent container with UV) using HPLC. We observed the degradation in the transparent containers faster than Amber colour container at 90 minutes, therefore, the experimental duration was extended up to 360 minutes for Transparent container with UV treatment.

[0089] Table-17: NCNF Photo-Stability Study: | Transparent container at UV for 360 minutes | 63.14 | 76.24 | 73.51 | 74.32 |

[0090] From the above experimental data, it is evident that NCNF formulations were more stable in Amber containers; however, it also showed better stability (16.4% to 20.74% higher) in comparison to commercial nano Curcumin in Transparent container under UV.

[0091] DEVELOPMENT OF NCNF WITH IMPROVED pH STABILITY:

[0092] Increase in alkaline stability will be helpful in increasing the absorption and thereby bioavailability of Curcumin. Therefore it is desired to have nano Curcumin formulations which can tolerate acidic as well as alkaline pH range.

[0093] Stock solution of 1000 ppm of all formulation commercial nano-Curcumin and NCNF-B variants were made by dissolving weighed amount in water, whereas commercial Curcumin solution was prepared in methanol.

[0094] From above prepared stock solutions, 100 pl samples were added into 400 pl of buffer solution of pH 1.2, 6.8 and 7.4, followed by addition of 1000 pl methanol. pH Stability Studies were carried out at various time period to assess the stability of the said formulations under different pH conditions.

[0095] Table-18: NCNF pH-Stability Study:

[0096] It was observed from the pH stability experiments, NCNF B variants are stable as compared to commercially available nano Curcumin and commercial Curcumin.

[0097] IMPROVEMENT IN STABILITY PARAMETERS:

[0098] Stability studies for the NCNF B variants were performed as per ICH guidelines. The observations for the stability of particle size, solubility, odour, colour, clarity -precipitation, etc. were carried out. Table-19: NCNF Stability Study (As per ICH Guidelines)

[0099] (Where d.nm is particle size Z average diameter in nm)

[0100] Table-20: NCNF Showing Solubility and Permeability Improvement

[0101] Table-21: NCNF Stability Study outcome The NCNF formulations of the present invention were stable and there was no variations observed post completion of Stability Studies.

[0102] In an embodiment, the present invention of Novel Curcumin Nano Formulation (NCNF), which depicts the clear cut advantage over existing Curcumin and nano Curcumin formulations known in art. The developed NCNF is highly stable with 100% solubility in water, enhanced permeability and potential efficacy evident through its high anti-oxidant and anti-inflammatory activities.

[0103] In an embodiment, the present invention NCNF formulations can offer improved therapeutic potential compared with existing commercial nano Curcumin and conventional Curcumin.

Claims

We Claim:

1. A curcumin nano-formulation with enhanced efficacy and bioavailability, comprising a) Diethylene glycol mono ethyl ether in a weight ranging from 140 to 210 mg; b) Medium-Chain Triglycerides in a weight of 90 to 110 mg; c) Polyoxyl 15-hydroxystearate in a weight of 90 to 160 mg; d) PEG-40 Hydrogenated Castor Oil in a weight of 90 to 210 mg; e) Polyoxyl 35 Castor Oil in a weight of 90 to 160 mg; f) Lauroyl Polyoxyl-32 glycerides and PEG 6000 in a weight of 40 to 110 mg; g) PEG-32 sterate in a weight of 140 to 210 mg; h) polyoxyethylene-polyoxypropylene in a weight of 90 to 120 mg; i) Propylene glycol caprylate and Propylene Glycol Mono and Di Caprylate in an amount of 80 to 120mg; j) polyoxyethylene sorbitan monooleate in a weight of 20 to 60 mg; k) propylene glycol caprylate and mixture of refined soybean oil, glyceryl distearate (C18) and polyglyceryl -3 dioleate (cl8:l), in an amount of 40 to llOmg; l) Curcumin in the amount / s of 50mg, 70mg and 90 mg.

2. A curcumin nano-formulation with enhanced efficacy and bioavailability as claimed in claim 1, comprising: a) Diethylene glycol mono ethyl ether in a weight ranging from 140 to 160 mg; b) Medium-Chain Triglycerides in a weight of 90 to 110 mg; c) PEG-40 Hydrogenated Castor Oil in a weight of 90 to 110 mg; d) Polyoxyl 35 Castor Oil in a weight of 140 to 160 mg; e) Lauroyl Polyoxyl-32 glycerides and PEG 6000 in a weight of 90 to 110 mg; f) PEG-32 sterate in a weight of 140 to 160 mg; g) polyoxyethylene sorbitan monooleate in a weight of 40 to 60 mg; h) mixture of propylene glycol caprylate and refined soybean oil, glyceryl distearate (C18) and polyglyceryl -3 dioleate (cl8:l) present in a weight of 40 to 60 mg; and i) curcumin in the amount / s of 50mg, 70mg and 90 mg.

3. The composition as claimed in claim 2, wherein: a) Diethylene glycol mono ethyl ether in a weight of 150 mg; b) Medium-Chain Triglycerides in a weight of 100 mg; c) PEG-40 Hydrogenated Castor Oil in a weight of 100 mg;d) Polyoxyl 35 Castor Oil in a weight of 150mg; e) Lauroyl Polyoxyl-32 glycerides and PEG 6000 in a weight of lOOmg; f) PEG-32 sterate in a weight of 150 mg; g) polyoxyethylene sorbitan monooleate in a weight of 50 mg; h) mixture of propylene glycol caprylate and refined soybean oil, glyceryl distearate (C18) and polyglyceryl -3 dioleate (cl8:l) present in a weight of 50 mg; and i) curcumin in the amount / s of 50mg, 70mg and 90 mg.

4. The composition as claimed in claim 2, wherein size of NCNF-A 50, NCNF-B 50, NCNF-B 70, NCNF-B 90 mg particle is less than 100 nm.

5. A method of preparing curcumin nano-formulation with enhanced efficacy and bioavailability as claimed in claim 1 or 2 comprising: a) weighing predetermined quantity of a diethylene glycol mono ethyl ether, Medium- Chain Triglycerides, Polyoxyl 35 Castor Oil, a PEG-40 Hydrogenated Castor Oil and a Lauroyl Polyoxyl-32 glycerides and PEG 6000 and preparing a mixture in vessel-A, followed by heating the mixture of vessel-A under stirring condition for 10-15 minutes at 60-75 °C; b) weighing predetermined quantity of a PEG-32 sterate, a Polyoxyethylene sorbitan monooleate, a propylene glycol caprylate and a mixture of refined soybean oil, glyceryl distearate (Cl 8) and polyglyceryl -3 dioleate (cl 8: 1) and preparing a mixture in vessel-B, followed by heating the mixture of vessel-B mildly at 45- 55 °C; c) adding predetermined quantity of curcumin into vessel A to form homogenous mixture using high a speed homogenizer for 10-15min at 8,000 - 10,000 rpm, under temperature of 40-50°C; and d) adding the preheated (45-55°C) mixture of vessel B into the homogenized solution obtained in step (c) followed by sonication for 30-35 minutes at 45-55°C and thereafter homogenization for 10-15 min at 8,000 - 10,000 rpm.

6. The method as claimed in claim 5, wherein Diethylene glycol mono ethyl ether is present in a weight of 150 mg; Medium-Chain Triglycerides is present in a weight of 100 mg; PEG-40 Hydrogenated Castor Oil is present in a weight of 100 mg; Polyoxyl 35 Castor Oil is present in a weight of 150mg; Lauroyl Polyoxyl-32 glycerides and PEG 6000 is present in a weight of lOOmg; PEG-32 sterate is present in a weight of 150 mg; polyoxyethylene sorbitan monooleate is present in a weight of 50 mg; mixtureof propylene glycol caprylate and refined soybean oil, glyceryl distearate (C18) and polyglyceryl -3 dioleate (cl8:l) present is present in a weight of 50 mg; and Curcumin is present in the amount / s of 50mg, 70mg and 90 mg.

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