FORM 2
THE PATENT ACT, 1970
(39 of 1970)
&
THE PATENT RULES, 2003
COMPLETE SPECIFICATION
(See section 10 and rule 13)
1. Title of the Invention
A NUTRACEUTICAL FORMULATION AND A PROCESS FOR PRODUCTION THEREOF
2. Applicants)
Name Nationality Address
TATA CHEMICALS INDIA BOMBAY HOUSE, 24 HOMI MODY
LIMITED STREET, MUMBAI - 400001
3. Preamble to the description
COMPLETE SPECIFICA TION
The following specification particularly describes the invention and the manner in which it is to
be performed.

The present disclosure relates to nutraceutical formulation of molecular complex of Curcumin and Molecular complex former and process for production thereof. In particular the invention relates to nutraceutical formulation of molecular complex of Curcumin and molecular complex former selected from Trehalose, Sucralose, Arabitol, Xylitol, Citric Acid, Carnosine, Maltose, Maltitol and mixture thereof having improved curcumin water solubility and a process for production thereof.
SUMMARY
A nutraceutical formulation of molecular complex of Curcumin and molecular complex former selected from Trehalose, Sucralose, Arabitol, Xylitol, Citric Acid, Carnosine, Maltose, Maltitol and mixture thereof is disclosed. A nutraceutical formulation comprises a molecular complex of Curcumin and Fructo-oligosaccharides. The molecular complex further comprises the improved water solubility and improved bioavailability.
A process for preparing a molecular complex of Curcumin and molecular complex former selected from Trehalose, Sucralose, Arabitol, Xylitol, Citric Acid, Carnosine, Maltose, Maltitol is disclosed. The process comprises mixing Curcumin and molecular complex former selected from Trehalose, Sucralose, Arabitol, Xylitol, Citric Acid, Carnosine, Maltose, Maltitol and mixture thereof in any molar ratios between 1:4 to 4: 1, followed by grinding to form a dry mixture; adding a solvent to the dry mixture followed by grinding to obtain a wet mixture; and air drying the wet mixture to obtain the molecular complex.
BACKGROUND

Curcumin is the major yellow pigment of turmeric, a commonly used spice, derived from the rhizome of the herb Curcuma Longa. Curcumin has been widely used as to promote health and treat and/or prevent disease and/or illnesses. The herb belongs to ginger family and turmeric widely used and cultivated in South Asia, particularly in Indian subcontinent. Turmeric is widely known for its medicinal activity for inflammation, skin wounds, pain relief etc. Curcumin is the active ingredient of the turmeric. Curcumin is not soluble in water and hence bioavailability of this compound is very poor.
BRIEF DESCRIPTION OF ACCOMPANYING FIGURES
Figure 1 illustrates a comparison powder X-ray diffraction (PXRD) profile of Curcumin, Trehalose and molecular complex of Curcumin and Trehalose.
Figure 2 illustrates a comparison powder X-ray diffraction (PXRD) profile of Curcumin, Sucralose and molecular complex of Curcumin and Sucralose.
Figure 3 illustrates a comparison powder X-ray diffraction (PXRD) profile of Curcumin, Arabitol and molecular complex of Curcumin and Arabitol.
Figure 4 illustrates a comparison powder X-ray diffraction (PXRD) profile of Curcumin, Xylitol and molecular complex of Curcumin and Xylitol.
Figure 5 illustrates a comparison powder X-ray diffraction (PXRD) profile of Curcumin, Citric Acid and molecular complex of Curcumin and Citric Acid.
Figure 6 illustrates a comparison powder X-ray diffraction (PXRD) profile of Curcumin, Carnosine and molecular complex of Curcumin and Carnosine.
Figure 7 illustrates a comparison powder X-ray diffraction (PXRD) profile of Curcumin, Maltose and molecular complex of Curcumin and Maltose.

Figure 8 illustrates a comparison powder X-ray diffraction (PXRD) profile of Curcumin, Maltitol and molecular complex of Curcumin and Maltitol.
Figure 9 illustrates the comparison Differential Scanning Calorimetry (DSC) profile of Curcumin, Trehalose and molecular complex of Curcumin and Trehalose.
Figure 10 illustrates the comparison Differential Scanning Calorimetry (DSC) profile of Curcumin, Sucralose and molecular complex of Curcumin and Sucralose.
Figure 11 illustrates the comparison Differential Scanning Calorimetry (DSC) profile of Curcumin, Arabitol and molecular complex of Curcumin and Arabitol.
Figure 12 illustrates the comparison Differential Scanning Calorimetry (DSC) profile of Curcumin, Xylitol and molecular complex of Curcumin and Xylitol.
Figure 13 illustrates the comparison Differential Scanning Calorimetry (DSC) profile of Curcumin, Citric Acid and molecular complex of Curcumin and Citric Acid.
Figure 14 illustrates the comparison Differential Scanning Calorimetry (DSC) profile of Curcumin, Carnosine and molecular complex of Curcumin and Carnosine.
Figure 15 illustrates the comparison Differential Scanning Calorimetry (DSC) profile of Curcumin, Maltose and molecular complex of Curcumin and Maltose.
Figure 16 illustrates the comparison Differential Scanning Calorimetry (DSC) profile of Curcumin, Maltitol and molecular complex of Curcumin and Maltitol.
Figure 17 illustrates the comparison infrared (IR) absorption profile Curcumin, Trehalose and of molecular complex of Curcumin and Trehalose.
Figure 18 illustrates the comparison infrared (IR) absorption profile Curcumin, Sucralose and of molecular complex of Curcumin and Sucralose.

Figure 19 illustrates the comparison infrared (IR) absorption profile Curcumin, Arabitol and of molecular complex of Curcumin and Arabitol.
Figure 20 illustrates the comparison infrared (IR) absorption profile Curcumin, Xylitol and of molecular complex of Curcumin and Xylitol.
Figure 21 illustrates the comparison infrared (IR) absorption profile Curcumin, Citric Acid and of molecular complex of Curcumin and Citric Acid.
Figure 22 illustrates the comparison infrared (IR) absorption profile Curcumin, Carnosine and of molecular complex of Curcumin and Carnosine.
Figure 23 illustrates the comparison infrared (IR) absorption profile Curcumin, Maltose and of molecular complex of Curcumin and Maltose.
Figure 24 illustrates the comparison infrared (IR) absorption profile Curcumin, Maltitol and of molecular complex of Curcumin and Maltitol.
Figure 25 illustrates the standard known concentration curve of Curcumin solubility using Ultra Violet-visible spectroscopy.
DETAILED DESCRIPTION
For the purpose of promoting an understanding of the principles of the invention, reference will now be made to embodiments 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 disclosed process, and such further applications of the principles of the invention 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.
Reference throughout this specification to "one embodiment" "an embodiment" or similar language means that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment of the present invention. Thus, appearances of the phrase "in one embodiment", "in an embodiment" and similar language throughout this specification may, but do not necessarily, all refer to the same embodiment.
Definitions:
Molecular complex: herein refers to a substance in a solid form or solid formulations, which
comprises at least two pure substances which interact with each other through hydrogen bonding
or any other non-covalent interactions to form molecular complex including co-crystals, solvates,
hydrates or eutectic combinations or solid solutions, in which at least one of the pure substance is
present in the solid form.
Nutraceuticals also known as phytochemicals, are natural, bioactive chemical compounds that
provide numerous physiological benefits, including, inter alia, disease/illness
prevention/treatment and health promotion. Nutraceuticals are used to achieve both long-term
and short-term health objectives.
Bioavailability
The U.S. Food and Drug Administration (FDA) define bioavailability as "the rate and extent to
which the active drug ingredient or therapeutic moiety is absorbed from a drug product and

becomes available at the site of drug action". Because in practice it is rare that active ingredient concentrations can be determined at the site of action.
The therapeutic effectiveness of an active ingredient depends upon the ability of the dosage form to deliver the active ingredient to its site of action at a rate and amount sufficient to elicit the desired pharmacological response. This attribute of the dosage form is referred to as physiologic availability, biologic availability or simply bioavailability.
For most active ingredients, the pharmacologic response can be related directly to the plasma levels. Thus the term bioavailability is defined as the rate and extent (amount) of absorption of unchanged active ingredient from its dosage form. It can also be defined as the rate and the extent to which the ingredients or active moiety is absorbed from the product and becomes available at the site of action. Blood level studies are the most common type of human or animal bioavailability studies, and are based on the assumption that there is a direct relationship between the concentration of active ingredient in blood or plasma and the concentration of active ingredient at the site of action. By monitoring the concentration in the blood, it is thus possible to obtain an indirect measure of active ingredient response. Following the administration of a single dose of an active ingredient, blood samples are drawn at specific time intervals and analyzed for active ingredient content. A profile is constructed showing the concentration of active ingredient in blood at the specific times the samples were taken. The key parameters to note are:
1. AUC, The area under the plasma concentration-time curve, The AUC is proportional to
the total amount of active ingredient reaching the systemic circulation, and thus
characterizes the extent of absorption.

2. Cmax, The maximum active ingredient concentration. The maximum concentration of active ingredient in the plasma is a function of both the rate and extent of absorption. Cmax will increase with an increase in the dose, as well as with an increase in the absorption rate.
3. Tmax, The time at which the Cmax occurs. The Tmax reflects the rate of active ingredient absorption, and decreases as the absorption rate increases.
Bioavailability (the rate and extent of active ingredient absorption) is generally assessed by the determination of these three parameters. Since the AUC is representative of, and proportional to, the total amount of active ingredient absorbed into the circulation, it is used to quantitate the extent of active ingredient absorption. Thus, the faster the absorption of an active ingredient the higher the maximum concentration will be and the less time it will take to reach the maximum concentration.
Improved solubility: as employed herein refer to a form of the curcumin that has increased solubility or dissolution rate relative to the least soluble form of the curcumin known.
The disclosure relates to nutraceutical formulation of molecular complex of Curcumin and molecular complex former selected from Trehalose, Sucralose, Arabitol, Xylitol, Citric Acid, Carnosine, Maltose, Maltitol and mixture thereof. In accordance with anaspect of the invention the nutraceutical formulation is the molecular complex of Curcumin and Molecular complex

former selected from Trehalose, Sucralose, Arabitol, Xylitol, Citric Acid, Carnosine, Maltose, Maltitol and mixture thereof having improved curcumin water solubility.
Chemically, curcumin is a bis-R,-unsaturated-diketone (commonly called diferuloylmethane), which exhibits keto-enol tautomerism having a predominant keto form in acidic and neutral solutions and stable enol form in alkaline medium. Commercial curcumin contains approximately 77% diferuloylmethane, 17% demethoxycurcumin, and 6% bisdemethoxycurcumin.
Curcumin refers to all polymorphs, solvates, and hydrates of the all curcuminoids, having the formula I, II and III, alone or in combination in any ratio:


Molecular complex former selected from Trehalose, Sucralose, Arabitol, Xylitol, Citric Acid, Carnosine, Maltose, Maltitol and mixture thereof refers to all polymorphs, solvates, and hydrates of the substance having the formula IV:



In accordance with an aspect, the nutraceutical formulation comprising curcumin and molecular complex former selected from Trehalose, Sucralose, Arabitol, Xylitoi, Citric Acid,

Carnosine, Maltose, Maltitol and mixture thereof of the proposed invention is having improved curcumin solubility in water.
In accordance with an aspect, the stoichiometric ratio of Curcumin and Molecular complex former selected from Trehalose, Sucralose, Arabitol, Xylitol, Citric Acid, Carnosine, Maltose, Maltitol and mixture thereof in the molecular complex is any molar ratios between 1:4 to 4: 1, preferably 1:1.
In accordance with an aspect, the water solubility of curcumin in Curcumin and molecular complex former selected from Trehalose, Sucralose, Arabitol, Xylitol, Citric Acid, Carnosine, Maltose, Maltitol and mixture thereof molecular complex is at least 0.1 microgram per milliliter (|ag/ml) of water. In accordance with an aspect the water solubility was checked in substantially pure water. The maximum water solubility of the curcumin has been reported 11 nano gram per milliliter by Ucisik M H et al {Journal of Nanobiotechnology 2013, 11:37).
In accordance with an aspect, molecular complex of curcumin and molecular complex former selected from Trehalose, Sucralose, Arabitol, Xylitol, Citric Acid, Carnosine, Maltose, Maltitol and mixture thereof of the proposed invention is having significantly different differential" scanning calorimetry melting peak and thermal behavior from the standard compounds. Differential scanning calorimetry analysis determines the temperature and heat flow associated with material transitions as a function of time and temperature. The change in the differential scanning calorimetry melting peak determines the formation of molecular complex of the proposed invention.
In accordance with an aspect, the invention provides a pharmaceutical, foodstuff, nutritional supplement, and nutritional composition comprising molecular complex of Curcumin

and molecular complex former selected from Trehalose, Sucralose, Arabitol, Xylitol, Citric Acid, Carnosine, Maltose, Maltitol and mixture thereof as described herewith.
The process comprises of preparing a mixture of Curcumin and molecular complex former selected from Trehalose, Sucralose, Arabitol, Xylitol, Citric Acid, Carnosine, Maltose, Maltitol and mixture thereof in different molar stoichiometric ratios, grinding the mixture, heating the ground mixture, cooling the heated mixture and grinding it to obtain molecular complex of Curcumin and molecular complex former selected from Trehalose, Sucralose, Arabitol, Xylitol, Citric Acid, Carnosine, Maltose, Maltitol and mixture thereof.
The grinding may be carried out in any suitable apparatus for grinding solids. Such apparatus includes but is not limited to mortar mills, vibrator mills or ball mills.
In accordance with an embodiment the ground mixture is heated at 60 to 80°C using but not limited to temperature control water bath with or without vacuum. The heating may be carried out under an inert atmosphere.
Any known method may be used for preparing molecular complex of Curcumin and molecular complex former selected from Trehalose, Sucralose, Arabitol, Xylitol, Citric Acid, Carnosine, Maltose, Maltitol and mixture thereof. By way of a specific example the process comprises of admixing Curcumin and molecular complex former selected from Trehalose, Sucralose, Arabitol, Xylitol, Citric Acid, Carnosine, Maltose, Maltitol and mixture thereof in a 1:1 stoichiometric ratio to form a dry mixture, grinding said dry mixture for a predetermined period of time, adding few drops of solvent to make it wet and grinding the wet mixture for a predetermined period of time under inert condition, heating this ground mixture at around 75 °C temperature water bath for a period 10 to 15 minutes under inert condition and cooling the back the heated ground mixture to room temperature to obtain the molecular complex of Curcumin

and Molecular complex former selected from Trehalose, Sucralose, Arabitol, Xylitol, Citric Acid, Carnosine, Maltose, Maltitol and mixture thereof.
The wet grinding and heating may be carried out under nitrogen atmosphere.
The grinding of the dry mixture may be carried out for 1 to 20 minutes. The grinding of the wet mixture may be carried out for 1-20 minutes.
The grinding may be carried out in any suitable apparatus for grinding solids. Such apparatus includes but is not limited to mortar mills, vibrator mills or ball mills.
In accordance with an embodiment the solvent is any suitable solvent including but not limited to water, acetonitrile, ethanol, methanol, ethyl acetate, acetone or their mixture. The amount of solvent added is in a range of 0.1 ml to 5 ml per 1 gram of combined weight of Curcumin and molecular complex former selected from Trehalose, Sucralose, Arabitol, Xylitol, Citric Acid, Carnosine, Maltose, Maltitol and mixture thereof.
In accordance with an embodiment the nutraceutical formulation comprising the molecular complex of Curcumin and molecular complex former selected from Trehalose, Sucralose, Arabitol, Xylitol, Citric Acid, Carnosine, Maltose, Maltitol and mixture thereof of the present disclosure as an active ingredient may be provided as a pharmaceutical composition for preventing or treating inflammation, skin wounds, pain relief, indigestion or other common aliment. The composition of the present disclosure may comprise molecular complex of Curcumin and molecular complex former selected from Trehalose, Sucralose, Arabitol, Xylitol, Citric Acid, Carnosine, Maltose, Maltitol and mixture thereof of the present disclosure in an amount of 0.001-99.999% (w/w) as well as an excipient as balance.
In accordance with an embodiment the nutraceutical formulation comprising the molecular complex of Curcumin and molecular complex former selected from Trehalose,

Sucralose, Arabitol, Xylitol, Citric Acid, Carnosine, Maltose, Maltitol and mixture thereof of the present disclosure may be formulated into powder, granule, tablet, pill, sugar-coated tablet, capsule, liquid, gel, syrup, suspension, wafer, or the like together with an adequate excipient for oral administration according to a method known in the art.
In accordance with an embodiment the nutraceutical formulation comprising the molecular complex of Curcumin and Molecular complex former selected from Trehalose, Sucralose, Arabitol, Xylitol, Citric Acid, Carnosine, Maltose, Maltitol and mixture thereof of the present disclosure is a food additive.
EXAMPLES
Example 1: Molecular Complex preparation:
Curcumin (Sigma-Aldrich®) and Molecular complex former selected from Trehalose, Sucralose, Arabitol, Xylitol, Citric Acid, Carnosine, Maltose, Maltitol and mixture thereof were weighed in 1:1 molar ratios as separate samples for different experiments and ground using mortar and pestle for 5 minutes to make a homogenous mixture followed making paste under inert condition (Nitrogen atmosphere) with few drops of water added to it. Heating the mixture around 70 °C temperature in a control water bath for 5-10 min under vacuum in a rotary evaporator. The resulted material was cooled to room temperature to obtain the molecular complex. Example 2: Molecular Complex preparation:
Curcumin and Molecular complex Citric Acid were weighed in 1:2 and 2:1 molar ratios as separate samples for different experiments and ground using mortar and pestle for 5 minutes to make a homogenous mixture followed making paste under inert condition (Nitrogen atmosphere) with few drops of water added to it. Heating the mixture around 70 °C temperature in a control

water bath for 5-10 min under vacuum in a rotary evaporator. The resulted material was cooled to room temperature to obtain the molecular complex. Example 3: Powder X-ray Diffraction Technical Details:
Powder X-ray Diffraction (PXRD) profiles were obtained using PANalytical "X"pertPRO diffractometer. PXRD profile data presented for the region where significant peaks were observed. Analysis:
Molecular complexes of Curcumin and Molecular complex former selected from Trehalose, Sucralose, Arabitol, Xylitol, Citric Acid, Carnosine, Maltose, Maltitol and mixture thereof gave different PXRD profile than pure Curcumin and molecular complex former selected from Trehalose, Sucralose, Arabitol, Xylitol, Citric Acid, Carnosine, Maltose, Maltitol and mixture thereof. Figure 1 to 8 illustrate a comparative PXRD profile of samples of molecular complexes of Curcumin and Molecular complex former selected from Trehalose, Sucralose, Arabitol, Xylitol, Citric Acid, Carnosine, Maltose, Maltitol and mixture thereof. Example 4: Infrared Spectroscopy Technical Details:
Fourier transformed infrared spectra (FT-IR) were collected on a Bruker Vertex 70 model. Analysis:
FT-IR spectra of all the molecular complexes obtained from examples 1 were compared with individual compounds and it was found that there are significant changes in IR spectral band of functional group regions to confirm the formation of novel molecular complexes. Figure 17 to 24

exhibit the major IR peaks of the sample of molecular complexes of curcumin and Molecular complex former selected from Trehalose, Sucralose, Arabitol, Xylitol, Citric Acid, Carnosine, Maltose, Maltitol and mixture thereof. Example 5: Differential Scanning Calorimetry Technical Details:
Differential Scanning Calorimetry (DSC) thermograms of all the samples including samples from Example 1 were recorded on a Mettler DSC1 instrument. Analysis:
Molecular complexes of Curcumin and Molecular complex former selected from Trehalose, Sucralose, Arabitol, Xylitol, Citric Acid, Carnosine, Maltose, Maltitol and mixture thereof gave completely different DSC profile. Figure 9 to 16 illustrate the comparative DSC profile of samples of molecular complexes of Curcumin and molecular complex former selected from Trehalose, Sucralose, Arabitol, Xylitol, Citric Acid, Carnosine, Maltose, Maltitol and mixture thereof.
Example 6: Solubility study of molecular complex in water ethanol mixture: Solubility of curcumin in molecular complex of curcumin and molecular complex former selected from Trehalose, Sucralose, Arabitol, Xylitol, Citric Acid, Carnosine, Maltose, Maltitol and mixture thereof was checked in water containing 5% Ethanol. 150 mg of molecular complexes of Curcumin and molecular complex former selected from Trehalose, Sucralose, Arabitol, Xylitol, Citric Acid, Carnosine, Maltose, Maltitol and mixture thereof was weighed and transferred in a flask containing 50 mL of 5% ethanol water solution. Flask was kept on shaker at 100 rotation per minute (RPM) speed. 2 ml aliquots for different experiments were withdrawn from the flask at the time intervals of 2 hours, 24 hours and 48 hours followed by the aliquots

were filtered through 0.45 JJ. PTFE filter. Filtered sample was analyzed using Themo scientific, Ultimate 3000UItra high performance liquid chromatography (UHPLC) for the determination of Curcumin concentration, which provide solubility of Curcumin formulations. Solubility of molecular complexes of Curcumin and molecular complex former selected from Trehalose, Sucralose, Arabitol, Xylitol, Citric Acid, Carnosine, Maltose, Maltitol and mixture thereof was compared with the solubility of standard Curcumin using standard curve prepared from the known concentration shown in table 3. Figure 5 illustrates the Standard known concentration curve of Curcumin solubility using HPLC instrument.The table 4 illustrates the solubility of different ratios of Curcumin and molecular complex former selected from Trehalose, Sucralose, Arabitol, Xylitol, Citric Acid, Carnosine, Maltose, Maltitol and mixture thereof molecular complexes.
Table 3. Area Under the Curve (AUC) in HPLC profile of pure Curcumin in known concentration

Curcumin Concentration, (ng) Area Under the Curve (AUC)
0.8 0.06
1.6 0.10
2.4 0.14
3.2 0.17
Table 4: Solubility study of molecular complex in water ethanol mixture

Sr. No. Molecular complex (in ratio) Solubility
1 Curcumin 0.25
2 Curcumin and Trehalose (1:1) 0.59
3 Curcumin and Sucrslose (1:1) 0.42
4 Curcumin and Arabitol (1:1) 0.18
5 Curcumin and Xylitol (1:1) 0.40
6 Curcumin and Citric Acid (1:2) 0.30
7 Curcumin and Carnosine (1:1) 0.38
8 Curcumin and Maltose (1:1) 0.13
9 Curcumin and Maltitol (1:1) 0.48
Example 7: Bioavailability study of molecular complex in Rat Model:
Bioavailability (pharmacokinetics) of curcumin test was conducted as per OECD guidelines. Pure curcumin as control sample and molecular complexes of Curcumin and citric acid as exemplary product of the proposed invention was taken as test sample for the bioavailability study was conducted by orally feeding to male Sprague Dawley rats. Rats were taken in two groups the first group was for control group and the second group was for test sample group. In each group three male Sprague Dawley rats were taken for study. For control group dose of 300 mg/kg of Curcumin was administrated to each Rat and similarly an equivalent dose of 300 mg/kg

of Curcumin was administrated to each Rat in test sample group. Blood samples were collected at pre dose and at 0.25, 0.5, 1, 2, 4, 6, 8, and 24 h post-dose from each animal within ± 2 min of schedule time. At each time point, approximately 0.25 mL of blood was withdrawn and transferred to a labeled microfuge tube containing 200 mM K2EDTA solution (20 μL per mL of blood). Following sampling, equal volume of heparinized saline was replaced into the catheter. Blood was processed to collect plasma and stored below - 60 °C until their bioanalysis. Each plasma sample was analyzed for curcumin using a fit-for purpose liquid chromatographic tandem mass spectrometric detection (LC-MS/MS) method with a lower limit of quantification of 0.5 ng/mL for curcumin. The pharmacokinetic parameters for free curcumin were calculated using the non-compartmental analysis tool of the validated Phoenix WinNonlin software (Version 6.3). Mean pharmacokinetic parameters of molecular complex of Curcumin and citric acid formulation and standard Curcumin is given in below Table 2: Table 2: Mean pharmacokinetic parameters of Curcumin

Treatment/ Group Sample Tmax (h) Cmax (ng/mL) AUClast (ng.h/mL) Relative bioavailability b
Control group Curcumin 6.0 (4.0-6.0) 9.09
±
1.88 35.8
± 5.61 NA
Test sample group Curcumin-Citric acid (1:2) 6.0 (6.0-8.0) 9.34
± 2.01 61.6
± 52.8 172
In the above table a Tmax has been reported as median (min-max), AUClast and nominal doses were used for bioavailability (F) calculation with respect to control group. NA: not applicable

INDUSTRIAL APPLICABILITY
The molecular complex of Curcumin and molecular complex former selected from Trehalose, Sucralose, Arabitol, Xylitol, Citric Acid, Carnosine, Maltose, Maltitol and mixture thereof has synergistic effect. It provides better Curcumin solubility in water. A soluble variant of Curcumin and Trehalose, Sucralose, Arabitol, Xylitol, Citric Acid, Carnosine, Maltose, Maltitol and mixture thereof would allow enhancement of bioavailability. The enhanced bioavailability leads to better absorption in body for better bio-efficacy of the active ingredient. It is used as nutraceutical.

We Claim:
1. A nutraceutical formulation comprising a molecular complex of Curcumin and Molecular complex former selected from Trehalose, Sucralose, Arabitol, Xylitol, Citric Acid, Carnosine, Maltose, Maltitol and mixture thereof having a water solubility at least 0.1 μg/ml.
2. The nutraceutical formulation as claimed in claim 1, wherein Curcumin and Molecular complex former selected from Trehalose, Sucralose, Arabitol, Xylitol, Citric Acid, Carnosine, Maltose, Maltitol and mixture thereof having improved bioavailability.
3. The nutraceutical formulation as claimed in claim 1, wherein Curcumin and Molecular complex former selected from Trehalose, Sucralose, Arabitol, Xylitol, Citric Acid, Carnosine, Maltose, Maltitol and mixture thereof in the molecular complex are in a stoichiometric ratio in a range of 1: 4 to 4 : 1.
4. The nutraceutical formulation as claimed in claim 2, wherein Curcumin and Molecular complex former selected from Trehalose, Sucralose, Arabitol, Xylitol, Citric Acid, Carnosine, Maltose, Maltitol and mixture thereof in the molecular complex are in a stoichiometric ratio in a range of 1: 1.
5. A process for preparing a molecular complex of Curcumin and Molecular complex former selected from Trehalose, Sucralose, Arabitol, Xylitol, Citric Acid, Carnosine, Maltose, Maltitol and mixture thereof, the process comprising:

mixing Curcumin and Molecular complex former selected from Trehalose, Sucralose,
Arabitol, Xylitol, Citric Acid, Carnosine, Maltose, Maltitol and mixture thereof in a
stoichiometric ratio in a range of 1: 4 to 4 : 1, followed by grinding to obtain a dry
mixture;
adding a solvent to the dry mixture followed by grinding to obtain a wet mixture; and
air drying the wet mixture to obtain the molecular complex having a improved
curcumin water solubility.
6. The process as claimed in claim 5, wherein the process further comprises heating the wet mixture at about 70°C prior to air drying.
7. The process as claimed in claim 6, wherein the wet mixture is heated under a nitrogen atmosphere.
8. The process as claimed in claim 5, wherein the solvent is added to the dry mixture in a range of 0.5 ml to 10 ml with respect to each gram of combined weight of Curcumin and Molecular complex former selected from Trehalose, Sucralose, Arabitol, Xylitol, Citric Acid, Carnosine, Maltose, Maltitol and mixture thereof.
9. The process as claimed in claim 5, wherein the solvent is selected from water, acetonitrile, ethanol, methanol, ethyl acetate, acetone and mixtures thereof.

10. The process as claimed in claim 5, wherein the solvent is added to the dry mixture in a range of 0.1ml to 5ml per 1 gram of combined weight of Curcumin and Molecular complex former selected from Trehalose, Sucralose, Arabitol, Xylitol, Citric Acid, Carnosine, Maltose, Maltitol and mixture thereof.
11. The process as claimed in claim 5, wherein the molecular complex of Curcumin and Molecular complex former selected from Trehalose, Sucralose, Arabitol, Xylitol, Citric Acid, Carnosine, Maltose, Maltitol and mixture thereof having curcumin water solubility at least 0.1 μg/ml.
12. The nutraceutical formulation as claimed in claim 5, wherein Curcumin and Molecular complex former selected from Trehalose, Sucralose, Arabitol, Xylitol, Citric Acid, Carnosine, Maltose, Maltitol and mixture thereof having improved bioavailability.