DESC:FIELD OF THE INVENTION
The present invention relates to a self-nano emulsifying drug delivery system for a high loading formulation for cholecalciferol. More specifically, the invention relates to self-nano emulsifying drug delivery system adsorbed on a powder substrate for increased rate of dissolution, increased permeability and increased bioavailability and stability.

BACKGROUND OF THE INVENTION
Cholecalciferol, commonly known as Vitamin D3, is an essential nutrient vital for the proper functioning of the human body. It plays a crucial role in calcium absorption, bone health, reabsorption of calcium and phosphate in kidney immune system modulation, and various other physiological processes. As such, it is a widely recognized and utilized supplement in healthcare and nutraceutical applications.
Cholecalciferol is a fat-soluble vitamin and one of the primary challenges associated with Cholecalciferol is its inherently low aqueous solubility. This limited solubility poses significant hurdles in achieving optimal bioavailability when administered orally. Traditional dosage forms often struggle to deliver sufficient quantities of Cholecalciferol to meet therapeutic requirements due to its poor dissolution properties.
The self-nanoemulsifying drug formulation for Cholecalciferol not only underscores the paramount importance of this essential vitamin in human health but also represents a groundbreaking innovation that has the potential to transform the landscape of Cholecalciferol supplementation. By addressing the challenges of solubility and bioavailability, this formulation holds the promise of improving health outcomes, reducing the burden of deficiency-related diseases, and enhancing the overall quality of life for individuals worldwide.
To address these issues and enhance the therapeutic potential of Cholecalciferol, there is a growing need for innovative pharmaceutical formulations. These formulations should not only improve the loading capacity of Cholecalciferol but also enhance its overall solubility and bioavailability, thereby maximizing its clinical benefits.
EP4009815A2 discloses a composition including a dispersion medium including: an aqueous solution; a first active ingredient; a flavor agent; and a first type of polymer; and a dispersed phase including: a population of particles, each particle including: a core including: a second active ingredient a second type of polymer; and an aqueous solution; a shell, substantially surrounding the core, the shell including: a third type of polymer; a plurality of lipophilic carriers; and a third active ingredient; and a plurality of emulsifying agents.

EA038458B1 discloses an invention relating to the field of pharmaceutical nano formulations, namely, to an aqueous nano dispersion of a lipophilic and hydrophobic bioactive compound with physical stability during at least 1 year at room temperature, comprising an aqueous dispersion medium, a dispersed phase and a surface active agent, wherein the dispersed phase comprises a bioactive compound and the dispersion medium comprises water and a nano dispersion stabilizer in minimum concentration of 30% w/v, wherein said nano dispersion stabilizer ranges in concentration from 15 to 70% w/v and consists of a monosaccharide, a disaccharide, at least one oligosaccharide selected from a gentianose, a maltotirose and a raffinose, a polysaccharide, at least one glycol selected from a propylene glycol or a polyethylene glycol, a polyol or combinations thereof. The invention also relates to a method for preparing such stable nano dispersion.
To overcome these challenges, the present invention introduces a self-nano emulsifying drug formulation for Cholecalciferol. This innovative formulation represents a significant advancement in the field of pharmaceuticals and nutraceuticals by offering a comprehensive solution to the limitations associated with Cholecalciferol delivery.

OBJECTIVE OF THE INVENTION
The main objective of the present invention is to provide a self-nanoemulsifying drug formulation for Cholecalciferol to enhance its solubility in water, since it is a fat- soluble vitamin and is poorly soluble in water.
Yet another advantage of the present invention is to provide aqueous dispersion of the particles in a size range of 40 nm-1500 nm.
Yet another objective of the present invention is to accommodate a significantly high loading of Cholecalciferol in comparison to traditional dosage forms to ensure a therapeutically effective dose in a smaller volume.
Yet another objective of the present invention is to provide steady release of cholecalciferol over time, reducing the dosage frequency.
Yet another objective of the present invention is to provide a versatile delivery system and not being restricted to a single form of dosage, to provide delivery in the form of capsules, tablets, liquids, or any other suitable form as per the patient preferences.
Yet another objective of the present invention is to provide a formulation with enhanced bioavailability.
Further objectives, advantages, and features of the present invention will become apparent from the detailed description provided herein below, in which various embodiments of the disclosed invention are illustrated by way of example.

SUMMARY OF THE INVENTION
A self-nano emulsifying drug formulation for cholecalciferol by multiple methods, the self-nano emulsifying drug formulation includes one active ingredient cholecalciferol, having a concentration range from 0.30% to 2.6%, one powder substrate having a concentration range from 80.00% to 99.00%, one oil phase having a concentration range from 0.1% to 0.5%, a surfactant one having a concentration range from 0.2% to 10.0%, a surfactant two having a concentration range from 0.1% to 5.0% and one co-surfactant having a concentration range from 0.1% to 5.0%. Herein, the active ingredient has a loading capacity ranging from 100 IU/g to 10,00,000 IU/g and has an increased rate of dissolution, increased rate of permeability, increased bioavailability of the active ingredient. Herein, the particle size of formulations have a nano globule of 40 nm to 1500 nm in aqueous environment.Herein, a method for adsorption of the self-nano emulsifying drug on the powder substrate to obtain a powder formulation is direct spraying method (DS) where the powder substrate is heated, blended and the cooled self-nano-emulsified formulation is sprayed on this powder substrate to form the cholecalciferol formulation. Herein, another method for adsorption of the self-nano emulsifying drug on the powder substrate to obtain a powder formulation is spontaneous emulsification and lyophilization (SELM) where aqueous emulsification of the self-nano emulsified formulation and powder substrate are done, and both are blended together, hereafter the formulation is converted into a powder formulation through lyophilisation and another method for adsorption of the self-nano emulsifying drug on the powder substrate to obtain a powder formulation is spontaneous emulsification and vacuum drying (SEVDM) where self-nano emulsified formulation is added to an aqueous buffer and powder substrate is added to this formulation gradually, the mixed formulation is heated in a vacuum dryer till dry lumps are formed and the dry lumps are crushed to obtain the powdered cholecalciferol formulation.
The main advantage of the present invention is that it provides a self-nanoemulsifying drug formulation for Cholecalciferol to enhance its solubility in water, since it is a fat-soluble vitamin and is poorly soluble in water.
Yet another advantage of the present invention is that aqueous dispersion of the system provides a particle size range of 40nm-1500nm.
Yet another advantage of the present invention is that it accommodates a significantly high loading of Cholecalciferol in comparison to traditional dosage forms to ensure a therapeutically effective dose in a smaller volume.
Yet another advantage of the present invention is that it provides steady release of cholecalciferol over time, reducing the dosage frequency.
Yet another advantage of the present invention is that it provides a versatile delivery system and not being restricted to a single form of dosage, to provide delivery in the form of capsules, tablets, liquids, or any other suitable form as per the patient preferences.
Yet another advantage of the present invention is that it provides a formulation with enhanced bioavailability.
Further objectives, advantages, and features of the present invention will become apparent from the detailed description provided herein below, in which various embodiments of the disclosed invention are illustrated by way of example.

BRIEF DESCRIPTION OF DRAWINGS
The accompanying drawings are incorporated in and constitute a part of this specification to provide a further understanding of the invention. The drawings illustrate one embodiment of the invention and together with the description, serve to explain the principles of the invention.
FIG. 1 describes direct spaying method
FIG. 2 describes composition of NAV-D powder (VD0105_1)
FIG. 3 describes composition of NAV-D powder VD3107_3

DETAILED DESCRIPTION OF THE INVENTION
Definition
The term “a” or “an”, as used herein, is defined as one. The term “plurality”, as used herein, is defined as two as or more than one. The term “another”, as used herein, is defined as at least a second or more. The terms “including” and/or “having”, as used herein, are defined as comprising (i.e., open language).
The term “comprising” is not intended to limit the present invention with such terminology rather is used in a wider sense. Any invention using the term comprising could be separated into one or more claims using “consisting” or “consisting of”. The term “comprising” may be used interchangeably with the terms “having” or “containing”.
Reference in this document to “one embodiment”, “certain embodiments”, “an embodiment”, “another embodiment”, and “yet another embodiment” or similar terms, throughout the document means that a specific feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment of the present invention. Thus, the appearances of such phrases in various places, this specification throughout are not necessarily all referring to the same embodiment. Furthermore, the specific features, structures, or characteristics are combined in any suitable manner in one or more embodiments without limitation.
The term “or” as used herein is to be interpreted as inclusive or meaning any one or more combinations. Therefore, “A, B or C” means any of the following: “A; B; C; A and B; A and C; B and C; A, B and C”. An exception to this definition will occur only when a combination of elements, functions, steps, or acts are in mutually exclusive, inherently.
As used herein, the term "one or more" generally refers to, but is not limited to, singular as well as the plural form of the term.
FIG. 1 describes direct spaying method for the adsorption of SNEDS onto a powder substrate
FIG. 2 describes an example composition of NAV-D powder (VD0105_1) direct spraying method
FIG. 3 describes an example composition of NAV-D powder (VD3107_3) direct spraying method

The present invention relates to a self-nano emulsifying drug formulation for cholecalciferol by multiple methods. The self-nano emulsifying drug formulation includes an active ingredient, a powder substrate, an oil phase, a surfactant one, a surfactant two and a co-surfactant. The active ingredient cholecalciferol has a concentration range from 0.3% to 2.6%. The powder substrate has a concentration range from 80.00% to 99.90%. In an embodiment, the powder substrate includes but is not limited to, lactose monohydrate, corn starch, dicalcium phosphate, potato starch, rice starch, tapioca starch, calcium carbonate, sorbitol, trehalose, mannitol, maltodextrin, polyvinyl alcohol, microcrystalline cellulose, cyclodextrin, lactose and combination thereof. The oil phase has a concentration range from 0.1% 5 to 0.5%. In an embodiment, the oil phase includes but is not limited to, oleic acid, olive oil, soybean oil, flaxseed oil, glyceryl monolinoleate, canola oil, cotton seed oil, rice bran oil, hazelnut oil, glyceryl palmostearate, sunflower oil, hempseed oil, castor oil, medium chain triglycerides and palm oil. The surfactant one has a concentration range from 0.1% to 2.0%. The surfactant one includes but is not limited to, polyoxyl-32 stearate, lauroyl polyoxyl-6 glyceride, caprylic/capric triglycerides, polyoxyl 35 castor oil, polyethylene glycol palmitostearate, glyceryl behenate, sorbitan monooleate, propylene glycol monolaurate, stearoyl polyoxyl-32 glycerides, sorbitan monolaurate, polyoxylglycerides/ oleoyl polyoxyl-6 glycerides and polyethylene glycol, peg -32 stearate, caprylocapropyl polyoxyl-8 glycerides, peg-8 capric glycerides. The surfactant two has a concentration range from 0.1% to 1.0%. The surfactant two includes but is not limited to, polysorbate 20, propylene glycol monolaurate, glyceryl distearate, polyethylene glycol stearate, polyoxyl 35 castor oil, polyglyceryl-3 oleate, polyoxylglycerides/ oleoyl polyoxyl-6 glycerides, polyoxyl-32 stearate, caprylic/capric triglyceride and lauroyl polyoxyl-6 glycerides, lauroyl polyoxyl-32 glyceride, polysorbates, sorbitans. The co-surfactant has a concentration range from 0.1% to 1.0%. The co-surfactant includes but is not limited to, ethylhexylglycerin, polysorbate 20, polyethylene glycol 200, polyethylene glycol 400, isostearyl isostearate, polyvinyl alcohol, diethylhexyl carbonate, isopropyl myristate, isopropyl palmitate, di-isopropyl adipate, ethylhexylglycerin, caprylocapropyl polyoxyl-8 glycerides caprylic acid, ethanol, sorbitan esters, polysorbates, glycol esters, fatty alcohols, cetyl alcohol, stearyl alcohol, lecithin, capric triglycerides, medium chain triglycerides, di-isopropyl dimer dilinoleate, castor oil, polyglyceryl esters, glyceryl stearate, caprylyl glycol, isostearyl neopentanoate, polyglyceryl polyricinoleate, Coco-Caprylate/Caprate, Sucrose Esters, Triethyl Citrate, Hydrogenated Castor Oil, and Diethylene glycol monoethyl ether. Herein, the present invention is characterized in that the active ingredient has a loading capacity range from 100 IU/g to 10,00,000 IU/g with an increased rate of dissolution, an increased rate of permeability and increased bioavailability of the active ingredient. Herein, the particle size of formulations have a nano globule of 40 nm to 1500 nm in aqueous environment.
The present invention herein includes a method for adsorption of the self-nano emulsifying drug on the powder substrate to obtain a powder formulation used is direct spraying method (DS) where the powder substrate is heated, blended and the cooled self-nano-emulsified formulation is sprayed on the powder substrate to form the cholecalciferol 5 formulation.
Herein, another method for adsorption of the self-nano emulsifying drug on the powder substrate to obtain a powder formulation is spontaneous emulsification and lyophilization (SELM) where aqueous emulsification of the self-nano emulsified formulation and powder substrate are done, and both are blended together, hereafter the formulation is converted into a powder formulation through lyophilization.
Herein, another method for adsorption of the self-nano emulsifying drug on the powder substrate to obtain a powder formulation is spontaneous emulsification and vacuum drying (SEVDM) where self-nano emulsified formulation is added to an aqueous buffer and powder substrate is added to this formulation gradually, the mixed formulation is heated in a vacuum dryer till dry lumps are formed and the dry lumps are crushed to obtain the powdered cholecalciferol formulation.

In an embodiment, the method for preparing the self-nano emulsifying formulation includes;

the active ingredient was mixed in various oil phases, surfactants and co-surfactants to form self-nano emulsifying drugs;
sound waves are used to agitate the particles in the various self-nano emulsifying drugs to further dissolute the particles in the drug;
the drugs are placed under a microscope, assessed and tabulated in three categories of solubility;
the surfactant one, the surfactant two, the oil phase and the co-surfactant are selected on the basis of solubility data;
the powder substrate is selected on the basis of characteristics and compatibility with the self-nano emulsifying drug; and
the self-nano emulsifying drug is adsorbed on the powder substrate by a method of direct spraying method (DS) including:
the powder substrate is heated at 60? for at least 4 hours,
the heated powder substrate is blended in a blender,
the self-nano emulsified formulation is cooled to attain a temperature less than 10?,
the cooled formulation is sprayed through a nozzle under pressurized nitrogen on the powder substrate,
the formulation is sprayed for a stipulated time to form the powdered formulation of cholecalciferol.

In an embodiment, the method for preparing the self-nano emulsifying formulation includes;

the active ingredient was mixed in various oil phases, surfactants and co-surfactants to form self-nano emulsifying drugs;
sound waves are used to agitate the particles in the various self-nano emulsifying drugs to further dissolute the particles in the drug;
the drugs are placed under a microscope, assessed and tabulated in three categories of solubility;
the surfactant one, the surfactant two, the oil phase and the co-surfactant are selected on the basis of solubility data;
the powder substrate is selected on the basis of characteristics and compatibility with the self-nano emulsifying drug; and
the self-nano emulsifying drug is adsorbed on the powder substrate by a method of spontaneous emulsification and lyophilization method (SELM) including:
aqueous emulsification of the self-nano emulsified formulation is performed under inert atmosphere to obtain a particular globular sized formulation,
aqueous emulsification is performed by use of sound waves to agitate the particles and/or creating high pressure to disintegrate the particles using shear forces and/or creating high pressures, sheer, turbulence, acceleration and impact,
the powder substrate is dispersed in a separate container by use of sound waves to agitate the particles and/or creating high pressure to disintegrate the particles using shear forces and/or creating high pressures, sheer, turbulence, acceleration and impact,
the self-nano emulsified particles and the powder substrate are blended together to form a homogenous solution,
the blended solution is dried by the method of removing water from the formulation after freeze drying, known as lyophilization to form a powder formulation of cholecalciferol.

In an embodiment, the method for preparing the self-nano emulsifying formulation includes:

the active ingredient was mixed in various oil phases, surfactants and co-surfactants to form self-nano emulsifying drugs;
sound waves are used to agitate the particles in the various self-nano emulsifying drugs to further dissolute the particles in the drug;
the drugs are placed under a microscope, assessed and tabulated in three categories of solubility;
the surfactant one, the surfactant two, the oil phase and the co-surfactant are selected on the basis of solubility data;
the powder substrate is selected on the basis of characteristics and compatibility with the self-nano emulsifying drug; and
the self-nano emulsifying drug is adsorbed on the powder substrate by a method of spontaneous emulsification and vacuum drying method (SEVDM) including:
the self-nano emulsifying formulation is mixed in aqueous buffer to form nano emulsion,
the solid substrate is added gradually to the nano emulsion with continuous stirring under high pressure, turbulence, acceleration and impact to make the solution stable,
the formulation is spread in a vacuum dryer and heated to at least 50? till dry lumps are obtained,
the dry lumps are crushed in a mill and sifted to obtain the powder formulation of cholecalciferol.
Herein, the formulation in powder form has better stability with respect to pure vitamin D (cholecalciferol) as well as aqueous emulsion thereof.

In an embodiment, the present invention relates to a self-nano emulsifying drug formulation for cholecalciferol by multiple methods. The self-nano emulsifying drug formulation includes one or more active ingredients, one or more powder substrates, one or more oil phases, one or more surfactants one, one or more surfactants two and one or more co-surfactants. The one or more active ingredient cholecalciferol has a concentration range from 0.3% to 2.6%. The one or more powder substrates have a concentration range from 80.00% to 99.90%. In an embodiment, the one or more powder substrates includes, but are not limited to, lactose monohydrate, corn starch, dicalcium phosphate, potato starch, rice starch, tapioca starch, calcium carbonate, sorbitol, trehalose, mannitol, maltodextrin, polyvinyl alcohol, microcrystalline cellulose, cyclodextrin, lactose and combination thereof. The one or more oil phases have a concentration range from 0.1% to 0.5%. In an embodiment, the one or more oil phases includes but are not limited to, oleic acid, olive oil, soybean oil, flaxseed oil, glyceryl monolinoleate, canola oil, cotton seed oil, rice bran oil, hazelnut oil, glyceryl palmostearate, sunflower oil, hempseed oil, castor oil, medium chain triglycerides and palm oil. The one or more surfactants one have a concentration 5 range from 0.1% to 2.0%. The one or more surfactants one includes but are not limited to polyoxyl-32 stearate, lauroyl polyoxyl-6 glyceride, caprylic/capric triglycerides, polyoxyl 35 castor oil, polyethylene glycol palmitostearate, glyceryl behenate, sorbitan monooleate, propylene glycol monolaurate, stearoyl polyoxyl-32 glycerides, sorbitan monolaurate, polyoxylglycerides/ oleoyl polyoxyl-6 glycerides and polyethylene glycol, peg -32 stearate, caprylocapropyl polyoxyl-8 glycerides, peg-8 capric glycerides. The one or more surfactants two have a concentration range from 0.1% to 1.0%. The one or more surfactants two includes but are not limited to polysorbate 20, propylene glycol monolaurate, glyceryl distearate, polyethylene glycol stearate, polyoxyl 35 castor oil, polyglyceryl- 3 oleate, polyoxylglycerides/ oleoyl polyoxyl-6 glycerides, polyoxyl-32 stearate, caprylic/capric triglyceride and lauroyl polyoxyl-6 glycerides, lauroyl polyoxyl-32 glyceride, polysorbates, sorbitans. The one or more cosurfactants have a concentration range from 0.1% to 1.0%. The one or more cosurfactants includes but are not limited to ethylhexylglycerin, polysorbate 20, polyethylene glycol 200, polyethylene glycol 400, isostearyl isostearate, polyvinyl alcohol, diethylhexyl carbonate, isopropyl myristate, isopropyl palmitate, di-isopropyl adipate, ethylhexylglycerin, caprylocapropyl polyoxyl-8 glycerides caprylic acid, ethanol, sorbitan esters, polysorbates, glycol esters, fatty alcohols, cetyl alcohol, stearyl alcohol, lecithin, capric triglycerides, medium chain triglycerides, di-isopropyl dimer dilinoleate, castor oil, polyglyceryl esters, glyceryl stearate, caprylyl glycol, isostearyl neopentanoate, polyglyceryl polyricinoleate, Coco-Caprylate/Caprate, Sucrose Esters, Triethyl Citrate, Hydrogenated Castor Oil, and Diethylene glycol monoethyl ether.

Herein, the present invention is characterized in that the active ingredient has a loading capacity range from 100 IU/g to 10,00,000 IU/g with an increased rate of dissolution, an increased rate of permeability and increased bioavailability of the active ingredient. Herein, the particle size of formulations have a nano globule of 40 nm to 1500 nm in aqueous environment.

In an embodiment, the present invention herein includes a method for adsorption of the self-nano emulsifying drug on the powder substrate to obtain a powder formulation used is direct spraying method (DS) where the one or more powder substrates are heated, blended and the cooled self-nano-emulsified formulation is sprayed on the powder substrate to form the cholecalciferol formulation.
Herein, another method for adsorption of the self-nano emulsifying drug on the
powder substrate to obtain a powder formulation is spontaneous emulsification and lyophilization (SELM) where aqueous emulsification of the self-5 nano emulsified formulation and powder substrate are done, and both are blended together, hereafter the formulation is converted into a powder formulation through lyophilization.

Herein, another method for adsorption of the self-nano emulsifying drug on the powder substrate to obtain a powder formulation is spontaneous emulsification and vacuum drying (SEVDM) where self-nano emulsified formulation is added to an aqueous buffer and powder substrate is added to this formulation gradually, the mixed formulation is heated in a vacuum dryer till dry lumps are formed and the dry lumps are crushed to obtain the powdered cholecalciferol formulation.

In an embodiment, the method for preparing the self-nano emulsifying formulation includes;

the one or more active ingredient was mixed in various oil phases, surfactants and co-surfactants to form self-nano emulsifying drugs;
sound waves are used to agitate the particles in the various self-nano emulsifying drugs to further dissolute the particles in the drug;
the drugs are placed under a microscope, assessed and tabulated in three categories of solubility;
the one or more surfactant one, the one or more surfactant two, the one or more oil phase and the one or more co-surfactant are selected on the basis of solubility data;
the one or more powder substrate is selected on the basis of characteristics and compatibility with the self-nano emulsifying drug; and
the self-nano emulsifying drug is adsorbed on the powder substrate by a method of direct spraying method (DS) including:
the one or more powder substrate is heated at 60? for at least 4 hours,
the heated powder substrate is blended in a blender,
the self-nano emulsified formulation is cooled to attain a temperature less than 10?,
the cooled formulation is sprayed through a nozzle under pressurized nitrogen on the powder substrate,
the formulation is sprayed for a stipulated time to form the powdered formulation of cholecalciferol.

In an embodiment, the method for preparing the self-nano emulsifying formulation includes;

the one or more active ingredient was mixed in various oil phases, surfactants and co-surfactants to form self-nano emulsifying drugs;
sound waves are used to agitate the particles in the various self-nano emulsifying drugs to further dissolute the particles in the drug;
the drugs are placed under a microscope, assessed and tabulated in three categories of solubility;
the one or more surfactant one, the one or more surfactant two, the one or more oil phase and the one or more co-surfactant are selected on the basis of solubility data;
the one or more powder substrate is selected on the basis of characteristics and compatibility with the self-nano emulsifying drug; and
the self-nano emulsifying drug is adsorbed on the powder substrate by a method of spontaneous emulsification and lyophilization method (SELM) including:
aqueous emulsification of the self-nano emulsified formulation is performed under inert atmosphere to obtain a particular globular sized formulation,
aqueous emulsification is performed by use of sound waves to agitate the particles and/or creating high pressure to disintegrate the particles using shear forces and/or creating high pressures, sheer, turbulence, acceleration and impact,
the one or more powder substrate is dispersed in a separate container by use of sound waves to agitate the particles and/or creating high pressure to disintegrate the particles using shear forces and/or creating high pressures, sheer, turbulence, acceleration and impact,
the self-nano emulsified particles and the powder substrate are blended together to form a homogenous solution,
the blended solution is dried by the method of removing water from the formulation after freeze drying, known as lyophilization to form a powder formulation of cholecalciferol.

In an embodiment, the method for preparing the self-nano emulsifying formulation includes;

the one or more active ingredient was mixed in various oil phases, surfactants and co-surfactants to form self-nano emulsifying drugs;
sound waves are used to agitate the particles in the various self-nano emulsifying drugs to further dissolute the particles in the drug;
the drugs are placed under a microscope, assessed and tabulated in three categories of solubility;
the one or more surfactant one, the one or more surfactant two, the one or more oil phase and the one or more co-surfactant are selected on the basis of solubility data;
the one or more powder substrate is selected on the basis of characteristics and compatibility with the self-nano emulsifying drug; and
the self-nano emulsifying drug is adsorbed on the powder substrate by a method of spontaneous emulsification and vacuum drying method (SEVDM) including:
the self-nano emulsifying formulation is mixed in aqueous buffer to form nano emulsion,
the solid substrate is added gradually to the nano emulsion with continuous stirring under high pressure, turbulence, acceleration and impact to make the solution stable,
the formulation is spread in a vacuum dryer and heated to at least 50? till dry lumps are obtained,
the dry lumps are crushed in a mill and sifted to obtain the powder formulation of cholecalciferol.
Herein, the formulation in powder form has better stability with respect to pure vitamin D (cholecalciferol) as well as aqueous emulsion thereof.

Example 1: 120000IU/g Cholecalciferol containing NAV-D powder by direct spraying method
A 120000IU/g Cholecalciferol containing NAV-D powder using lactose monohydrate powder as solid substrate was prepared as the composition in Fig. 2

Example 2: 120000IU/g Cholecalciferol containing NAV-D powder by direct spraying method
A 120000IU/g Cholecalciferol containing NAV-D powder using lactose monohydrate powder as solid substrate was prepared as the composition in Fig. 3 ,CLAIMS:1. A self-nano emulsifying drug formulation for cholecalciferol by multiple methods, the self-nano emulsifying drug formulation comprising of :

an at least one active ingredient cholecalciferol, having a concentration range from 0.30% to 2.6%;
an at least one powder substrate having a concentration range from 80.00% to 99.00%;
an at least one oil phase having a concentration range from 0.1% to 0.5%;
an at least a surfactant one having a concentration range from 0.2% to 10.0%;
an at least a surfactant two having a concentration range from 0.1% to 5.0%; and
an at least one co-surfactant having a concentration range from 0.1% to 5.0%,
characterized in that, the at least one active ingredient having a loading capacity range from 100 IU/g to 10,00,000 IU/g;
characterized in that, the particle size of formulations have a nano globule of 40 nm to 1500 nm in aqueous environment.

characterized in that, increased rate of dissolution, increased rate of permeability and increased bioavailability of the at least one active ingredient cholecalciferol;

wherein, the method for adsorption of the self-nano emulsifying drug on the powder substrate to obtain a powder formulation is direct spraying method (DS) where the powder substrate is heated, blended and the cooled self-nano-emulsified formulation is sprayed on this powder substrate to form the cholecalciferol formulation,

wherein, the method for adsorption of the self-nano emulsifying drug on the powder substrate to obtain a powder formulation is spontaneous emulsification and lyophilization (SELM) where aqueous emulsification of the self-nano emulsified formulation and powder substrate are done, and both are blended together, hereafter the formulation is converted into a powder formulation through lyophilization,

wherein, the method for adsorption of the self-nano emulsifying drug on the powder substrate to obtain a powder formulation is spontaneous emulsification and vacuum drying (SEVDM) where self-nano emulsified formulation is added to an aqueous buffer and powder substrate is added to this formulation gradually, the mixed formulation is heated in a vacuum dryer till dry lumps are formed and the dry lumps are crushed to obtain the powdered cholecalciferol formulation.

2. A self-nano emulsifying drug formulation for cholecalciferol by multiple methods as claimed in claim 1, wherein, the at least one powder substrate is selected from lactose monohydrate, corn starch dicalcium phosphate, potato starch, rice starch, tapioca starch, calcium carbonate, sorbitol, trehalose, mannitol, maltodextrin, polyvinyl alcohol, microcrystalline cellulose, cyclodextrin, lactose and combination thereof.

3. A self-nano emulsifying drug formulation for cholecalciferol by multiple methods as claimed in claim 1, wherein, the at least one oil phase is selected from oleic acid, olive oil, soybean oil, flaxseed oil, glyceryl monolinoleate, canola oil, cotton seed oil, rice bran oil, hazelnut oil, glyceryl palmostearate, sunflower oil, hempseed oil, castor oil, medium chain triglycerides palm oil, and sweet almond oil.

4. A self-nano emulsifying drug formulation for cholecalciferol by multiple methods as claimed in claim 1, wherein, the at least a surfactant one is selected from polyoxyl-32 stearate, lauroyl polyoxyl-6 glyceride, caprylic/capric triglycerides, polyoxyl 35 castor oil, polyethylene glycol palmitostearate, glyceryl behenate, sorbitan monooleate, propylene glycol monolaurate, stearoyl polyoxyl-32 glycerides, sorbitan monolaurate, polyoxylglycerides/ oleoyl polyoxyl-6 glycerides and polyethylene glycol, peg -32 stearate, caprylocapropyl polyoxyl-8 glycerides, peg-8 capric glycerides.

5. A self-nano emulsifying drug formulation for cholecalciferol by multiple methods as claimed in claim 1, wherein, the at least a surfactant two is selected from polysorbate 20, propylene glycol monolaurate, glyceryl distearate, polyethylene glycol stearate, polyoxyl 35 castor oil, polyglyceryl-3 oleate, polyoxylglycerides/ oleoyl polyoxyl-6 glycerides, polyoxyl-32 stearate, caprylic/capric triglyceride and lauroyl polyoxyl-6 glycerides, lauroyl polyoxyl-32 glyceride, polysorbates, sorbitans.

6. A self-nano emulsifying drug formulation for cholecalciferol by multiple methods as claimed in claim 1, wherein, the at least one co-surfactant is selected from ethylhexylglycerin, polysorbate 20, polyethylene glycol 200, polyethylene glycol 400, isostearyl isostearate, polyvinyl alcohol, diethylhexyl carbonate, isopropyl myristate, isopropyl palmitate, diisopropyl adipate, ethylhexylglycerin, caprylocapropyl polyoxyl-8 glycerides caprylic acid, ethanol, sorbitan esters, polysorbates, glycol esters, fatty alcohols, cetyl alcohol, stearyl alcohol, lecithin, capric triglycerides, medium chain triglycerides, di-isopropyl dimer dilinoleate, castor oil, polyglyceryl esters, glyceryl stearate, caprylyl glycol, isostearyl neopentanoate, polyglyceryl polyricinoleate, Coco-Caprylate/Caprate, Sucrose Esters, Triethyl Citrate, Hydrogenated Castor Oil, and Diethylene glycol monoethyl ether.

7. A self-nano emulsifying drug formulation for cholecalciferol by multiple methods as claimed in claim 1, wherein, a method for preparing the self-nano emulsifying formulation comprising:

the at least one active ingredient was mixed in various oil phases, surfactants and co-surfactants to form self-nano emulsifying drugs;
sound waves are used to agitate the particles in the various self-nano emulsifying drugs to further dissolute the particles in the drug;
the drugs are placed under a microscope, assessed and tabulated in three categories of solubility;
the at least a surfactant one, the at least a surfactant two, the at least one oil phase and the at least one co-surfactant are selected on the basis of solubility data;
the at least one powder substrate is selected on the basis of characteristics and compatibility with the self-nano emulsifying drug; and
the self-nano emulsifying drug is adsorbed on the powder substrate by a method of direct spraying method (DS) including:
the at least one powder substrate is heated at 60? for at least 4 hours,
the heated powder substrate is blended in a blender,
the self-nano emulsified formulation is cooled to attain a temperature less than 10?,
the cooled formulation is sprayed through a nozzle under pressurized nitrogen on the powder substrate,
the formulation is sprayed for a stipulated time to form the powdered formulation of cholecalciferol.

8. The formulation and method as claimed in claim 1, wherein, a method for preparing the self-nano emulsifying formulation comprising:

the at least one active ingredient was mixed in various oil phases, surfactants and co-surfactants to form self-nano emulsifying drugs;
sound waves are used to agitate the particles in the various self-nano emulsifying drugs to further dissolute the particles in the drug;
the drugs are placed under a microscope, assessed and tabulated in three categories of solubility;
the at least a surfactant one, the at least a surfactant two, the at least one oil phase and the at least one co-surfactant are selected on the basis of solubility data;
the at least one powder substrate is selected on the basis of characteristics and compatibility with the self-nano emulsifying drug; and
the self-nano emulsifying drug is adsorbed on the powder substrate by a method of spontaneous emulsification and lyophilization method (SELM) including:
aqueous emulsification of the self-nano emulsified formulation is performed under inert atmosphere to obtain a particular globular sized formulation,
aqueous emulsification is performed by use of sound waves to agitate the particles and/or creating high pressure to disintegrate the particles using shear forces and/or creating high pressures, sheer, turbulence, acceleration and impact,
the at least one powder substrate is dispersed in a separate container by use of sound waves to agitate the particles and/or creating high pressure to disintegrate the particles using shear forces and/or creating high pressures, sheer, turbulence, acceleration and impact,
the self-nano emulsified particles and the powder substrate are blended together to form a homogenous solution,
the blended solution is dried by the method of removing water from the formulation after freeze drying, known as lyophilization to form a powder formulation of cholecalciferol.

9. The formulation and method as claimed in claim 1, wherein, a method for preparing the self-nano emulsifying formulation comprising;

the at least one active ingredient was mixed in various oil phases, surfactants and co-surfactants to form self-nano emulsifying drugs;
sound waves are used to agitate the particles in the various self-nano emulsifying drugs to further dissolute the particles in the drug;
the drugs are placed under a microscope, assessed and tabulated in three categories of solubility;
the at least a surfactant one, the at least a surfactant two, the at least one oil phase and the at least one co-surfactant are selected on the basis of solubility data;
the at least one powder substrate is selected on the basis of characteristics and compatibility with the self-nano emulsifying drug; and
the self-nano emulsifying drug is adsorbed on the powder substrate by a method of spontaneous emulsification and vacuum drying method (SEVDM) including:
the self-nano emulsifying formulation is mixed in aqueous buffer to form nano emulsion,
the solid substrate is added gradually to the nano emulsion with continuous stirring under high pressure, turbulence, acceleration and impact to make the solution stable,
the formulation is spread in a vacuum dryer and heated to at least 50? till dry lumps are obtained,
the dry lumps are crushed in a mill and sifted to obtain the powder formulation of cholecalciferol.

10. A self-nano emulsifying drug formulation for cholecalciferol by multiple methods as claimed in claim 1, that formulation in powder form has better stability with respect to pure vitamin D (cholecalciferol) as well as aqueous emulsion thereof.