EARLIEST PRIORITY DATE:

This Application claims priority from a Complete patent application filed in India having Patent Application No. 202141020676, filed on May 06, 2021 and titled “A METHOD FOR PREPARATION OF A PHARMACEUTICAL EXCIPIENT FREE ORGANIC HERBAL TABLET FORMULATION”.

FIELD OF THE INVENTION

Embodiment of the present disclosure relates to a method of preparation of an organic tablet formulation. More particularly, a method for preparation of a pharmaceutical excipient free organic tablet formulation exhibiting improved compressibility.

BACKGROUND OF THE INVENTION

Pharmaceutical excipients are inert substances mainly used as vehicles and diluents for drugs. More specifically, the pharmaceutical excipients are substances that are included in a pharmaceutical dosage form not for their direct therapeutic action, but to aid the manufacturing process, to protect, support or enhance stability, or for bioavailability or patient acceptability.

As a result, the pharmaceutical excipients are supposed to be inactive, non-toxic and not interact with the active ingredients. However, the pharmaceutical excipients are known to cause some form of adverse reactions in some patients. These adverse reactions range from mild rashes to severe reactions.

Some of the common excipients include diluents, binders, compression aids, granulating agents, glidants and lubricants, tablet coatings and colouring agents. Further some common excipients with recorded adverse reactions include tartrazine, aspartame, benzalkonium chloride, sodium metabisulphite, propyl gallate, lactose, etc.

With this backdrop, it is known that the organic and herbal formulations are witnessing higher acceptability among the consumers during the last decade due to their safety as well as efficacy. Unlike, allopathic medications, herbal extracts are very safe and devoid of any side effects. The consumers worldwide are becoming more conscious for naturally derived products and avoiding synthetic chemical as excipients in their food, personal care products and daily health supplements. Many herbal products which are available in the market as tablets and capsules are using synthetic excipients such as binders, lubricants, diluents and preservatives such as Parabens and salts of benzoic acids, etc. These excipients and preservatives are reported to have toxic side effects.

Further it is also known that the pharmaceutical dosage forms such as tablets and capsules are required to have some physical attributes such as thickness, hardness, friability, disintegration time (DT), stability and delivery of the drug to give desired therapeutic benefits to the patient. These properties are achieved using the pharmaceutical excipients such as binders, lubricants and diluents.

It is a very important and challenging task to develop a process for organic and herbal formulations using herbal extract and plant powder/water extract of the respective plant and without using any synthetic pharmaceutical excipient and preservatives.

Therefore, there is a need for method for preparation of an organic formulation without use of any pharmaceutical excipients and also possesses improved properties which overcomes the aforementioned limitations.

SUMMARY OF THE INVENTION

In accordance with an embodiment of the present invention, a method for preparation of a pharmaceutical excipient free organic herbal tablet formulation, comprises of a) preparing a predetermined amount of an organic herbal water/ethanol extract and an organic herbal powder; b) sieving and blending the organic herbal water/ethanol extract and the organic herbal powder obtained from step (a);c) granulating the sieved and blended mixture of the organic herbal water/ethanol extract and the organic herbal powder from step (b) by using a granulation fluid of purified water; d) drying the granules obtained in step (c) in a tray drier at a temperature range of 60°C to 70°C for about 4 hours; e) milling the oversized granules comprising of the organic herbal water/ethanol extract and the organic herbal powder and the milled granules are sieved to obtain sized granules; f) blending the sized granules of the organic herbal water /ethanol extract and the organic herbal powder; and g) tableting the blended mixture of step (f) by compressing it using a compression machine to obtain the organic herbal tablet formulation exhibiting improved compressibility.

In accordance with an embodiment of the present invention, wherein the organic herbal water extract and the organic herbal powder is obtained from the at least one of Garcinia cambogia, Bacopa monneiri, Curcuma longa, Moringa oleifera and Triphala comprising of Emblica officinalis, Terminalia bellerica and Terminalia chebula.

In accordance with an embodiment of the present invention, wherein the organic herbal water extract and the organic powder is obtained from Garcinia cambogia, wherein the predetermined amount of Garcinia cambogia in the form of organic herbal water extract is 66.7% and organic herbal powder is 33.3%.

In accordance with an embodiment of the present invention, wherein the organic herbal ethanol extract and the organic herbal powder is obtained from Bacopa monneiri, wherein the predetermined amount of Bacopa monneiri in the form of organic herbal ethanol extract is 50% and the organic herbal powder is 50%.

In accordance with an embodiment of the present invention, wherein the organic herbal ethanol extract and the organic herbal powder is obtained from Curcuma longa, wherein the predetermined amount of Curcuma longa in the form of organic herbal ethanol extract is 50% and the organic herbal powder is 50%.

In accordance with an embodiment of the present invention, wherein the organic herbal water extract and the organic herbal powder is obtained from Moringa oleifera, wherein the predetermined amount of Moringa oleifera, in the form of organic herbal water extract is 16.70% and the organic herbal powder is 83.30%.

In accordance with an embodiment of the present invention, wherein the organic herbal water extract and the organic herbal powder is obtained from a Triphala comprising of Emblica officinalis, Terminalia bellerica and Terminalia chebula in a weight ratio of 1:1:1, wherein the predetermined amount of Triphala in the form of organic herbal water extract is 66.70% and the organic herbal powder is 33.30%.

In accordance with an embodiment of the present invention, wherein the granulation process of step (c) comprises of loading a predetermined amount of the organic herbal water /ethanol extract and the organic herbal powder into a rapid mixer granulator and blended for a time period of 5 minutes; adding the granulation fluid to the rapid mixer granulator over a time period of 3 minutes; continuous mixing by operating an impellar at a high speed with chopper ON’ for about 3 minutes; and adding an additional quantity of granulation fluid to obtain dough like mass of the organic herbal water/ethanol extract and the organic herbal powder.

In accordance with an embodiment of the present invention, wherein the drying process of step (d) comprises of drying the wet mass of the organic herbal water/ethanol extract and the organic herbal powder obtained from step (c); checking moisture content at regular time intervals; sifting the dried granules of the organic herbal water/ethanol extract and the organic herbal powder using a sifter fitted with sieve #20; collecting the sifted granules of the organic herbal water/ethanol extract and the organic herbal powder in a container; milling the oversized granules through a S.S multi mill fitted with 1.5mm screen with ‘Knives Forward’ direction; passing the milled granules through a sifter fitted with #20 sieve; and collecting the sized granules and adding them to the sifted granules and weighing and analysing the granules of the organic herbal water/ethanol extract and the organic herbal powder.

In accordance with an embodiment of the present invention, wherein the blending process of step (f) comprises of transferring the sized granules and fines of the organic herbal water/ethanol extract and the organic herbal powder generated to the blending area, wherein the temperature of the area is maintained at 25°C and relative humidity is maintained at 50%; loading the sized granules and the fines of the organic herbal water/ethanol extract and the organic herbal powder into a double cone blender; and blending the ingredients for a time period of 3minutes at 20 to 25rpm to obtain the blend of the organic herbal water extract and the organic herbal powder. In accordance with an embodiment of the present invention, wherein the compression process of step (g) comprises of adjusting the compression machine, wherein the temperature of the compression area is maintained at 25°C and the relative humidity at 50% and checking for appearance, average weight and individual weight, thickness, hardness, friability and disintegration of compressed tablets of the organic herbal water/ethanol extract and the organic herbal powder.

In accordance with another embodiment of the present invention, a pharmaceutical excipient free organic herbal tablet formulation exhibiting improved compressibility, comprises of a predetermined amount of organic herbal water/ethanol extract and organic herbal powder, wherein the organic herbal water/ethanol extract and the organic herbal powder is obtained from the at least one of Garcinia cambogia, Bacopa monneiri, Curcuma longa, Moringa oleifera and Triphala comprising of Emblica officinalis, Terminali abellerica and Terminalia chebula.

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

BRIEF DESCRIPTION OF THE DRAWINGS

The disclosure will be described and explained with additional specificity and detail with the accompanying figures in which:

FIG. 1 illustrates a method of preparation of a pharmaceutical excipient free organic herbal tablet formulation in accordance with an embodiment of the present disclosure.

FIG. 2 illustrates a high performance liquid chromatography (HPFC)of Garcinia cambogia extract in accordance with example 1 of the present disclosure. FIG. 3a and 3b illustrates a high performance liquid chromatography (HPLC) of Bacopa monneiri extract in accordance with example 1 of the present disclosure.

FIG. 4 illustrates a high performance liquid chromatography (HPLC)of Curcuma longa extract in accordance with example 1 of the present disclosure.

Further, those skilled in the art will appreciate that elements in the figures are illustrated for simplicity and may not have necessarily been drawn to scale. Furthermore, in terms of the construction of the device, one or more components of the device may have been represented in the figures by conventional symbols, and the figures may show only those specific details that are pertinent to understanding the embodiments of the present disclosure so as not to obscure the figures with details that will be readily apparent to those skilled in the art having the benefit of the description herein.

DETAILED DESCRIPTION OF THE INVENTION

For the purpose of promoting an understanding of the principles of the disclosure, reference will now be made to the embodiment illustrated in the figures and specific language will be used to describe them. It will nevertheless be understood that no limitation of the scope of the disclosure is thereby intended. Such alterations and further modifications in the illustrated system, and such further applications of the principles of the disclosure as would normally occur to those skilled in the art are to be construed as being within the scope of the present disclosure.

The terms "comprises", "comprising", or any other variations thereof, are intended to cover a non-exclusive inclusion, such that a process or method that comprises a list of steps does not include only those steps but may include other steps not expressly listed or inherent to such a process or method. Appearances of the phrase "in an embodiment", "in another embodiment" and similar language throughout this specification may, but not necessarily do, all refer to the same embodiment.

Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the art to which this disclosure belongs. The examples provided herein are only illustrative and not intended to be limiting. In the following specification and the claims, reference will be made to a number of terms, which shall be defined to have the following meanings. The singular forms “a”, “an”, and “the” include plural references unless the context clearly dictates otherwise.

The present disclosure discloses a method for preparation of a pharmaceutical excipient free organic herbal tablet formulation, wherein the method comprises of a) preparing a predetermined amount of an organic herbal water/ethanol extract and an organic herbal powder; b) sieving and blending the organic herbal water /ethanol extract and the organic herbal powder obtained from step (a); c) granulating the sieved and blended mixture of the organic herbal water/ethanol extract and the organic herbal powder from step (b) by using a granulation fluid of purified water; d) drying the granules obtained in step (c) in a tray drier at a temperature range of 60°C to 70°C for about 4 hours; e) milling the oversized granules comprising of the organic herbal water/ethanol extract and the organic herbal powder and the milled granules are sieved to obtain sized granules; f) blending the sized granules of the organic herbal water/ethanol extract and the organic herbal powder; and g) tableting the blended mixture of step (f) by compressing it using a compression machine to obtain the organic herbal tablet formulation exhibiting improved compressibility. FIG. 1 illustrates a method of preparation of a pharmaceutical excipient free organic herbal tablet formulation in accordance with an embodiment of the present disclosure.

According to an embodiment of the present invention, wherein the organic herbal water/ethanol extract and the organic herbal powder is obtained from the at least one of Garcinia cambogia, Bacopa monneiri, Curcuma longa, Moringa oleifera and Triphala comprising of Emblica officinalis, Terminalia bellerica and Terminalia chebula.

According to an embodiment of the present invention, wherein the organic herbal water extract and the organic powder is obtained from Garcinia cambogia, wherein the predetermined amount of Garcinia cambogia in the form of organic herbal water extract is 66.7% and organic herbal powder is 33.3%.

According to an embodiment of the present invention, wherein the organic herbal ethanol extract and the organic herbal powder is obtained from Bacopa monneiri, wherein the predetermined amount of Bacopa monneiri in the form of organic herbal ethanol extract is 50% and the organic herbal powder is 50%.

According to an embodiment of the present invention, wherein the organic herbal ethanol extract and the organic herbal powder is obtained from Curcuma longa, wherein the predetermined amount of Curcuma longa in the form of organic herbal ethanol extract is 50% and the organic herbal powder is 50%.

According to an embodiment of the present invention, wherein the organic herbal water extract and the organic herbal powder is obtained from Moringa oleifera, wherein the predetermined amount of Moringa oleifera in the form of organic herbal water extract is 16.70% and the organic herbal powder is 83.30%.

According to an embodiment of the present invention, wherein the organic herbal water extract and the organic herbal powder is obtained from a Triphala comprising of Emblica officinalis, Terminalia bellerica and Terminalia chebula in a weight ratio of 1 : 1 : 1 , wherein the predetermined amount of Triphala in the form of organic herbal water extract is 66.70% and the organic herbal powder is 33.30%.

According to an embodiment of the present invention, wherein the granulation process of step (c) comprises of loading a predetermined amount of the organic herbal water/ethanol extract and the organic herbal powder into a rapid mixer granulator and blended for a time period of 5 minutes; adding the granulation fluid to the rapid mixer granulator over a time period of 3 minutes; continuous mixing by operating an impellar at a high speed with chopper ON’ for about 3 minutes; and adding an additional quantity of granulation fluid to obtain dough like mass of the organic herbal water/ethanol extract and the organic herbal powder.

According to an embodiment of the present invention, wherein the drying process of step (d) comprises of drying the wet mass of the organic herbal water/ethanol extract and the organic herbal powder obtained from step (c); checking moisture content at regular time intervals; sifting the dried granules of the organic herbal water/ethanol extract and the organic herbal powder using a sifter fitted with sieve #20; collecting the sifted granules of the organic herbal water/ethanol extract and the organic herbal powder in a container; milling the oversized granules through a S.S multi mill fitted with 1.5mm screen with ‘Knives Forward’ direction; passing the milled granules through a sifter fitted with #20 sieve; and collecting the sized granules and adding them to the sifted granules and weighing and analysing the granules of the organic herbal water/ethanol extract and the organic herbal powder.

According to an embodiment of the present invention, wherein the blending process of step (f) comprises of transferring the sized granules and fines of the organic herbal water/ethanol extract and the organic herbal powder generated to the blending area, wherein the temperature of the area is maintained at 25°C and relative humidity is maintained at 50%; loading the sized granules and the fines of the organic herbal water /ethanol extract and the organic herbal powder into a double cone blender; and blending the ingredients for a time period of 3minutes at 20 to 25rpm to obtain the blend of the organic herbal water/ethanol extract and the organic herbal powder.

According to an embodiment of the present invention, wherein the compression process of step (g) comprises of adjusting the compression machine, wherein the temperature of the compression area is maintained at 25°C and the relative humidity at 50% and checking for appearance, average weight and individual weight, thickness, hardness, friability and disintegration of compressed tablets of the organic herbal water/ethanol extract and the organic herbal powder.

According to another embodiment of the present invention, a pharmaceutical excipient free organic herbal tablet formulation exhibiting improved compressibility, comprises of: a predetermined amount of organic herbal water/ethanol extract and organic herbal powder, wherein the organic herbal water extract and the organic herbal powder is obtained from the at least one of Garcinia cambogia, Bacopa monneiri, Curcuma longa, Moringa oleifera and Triphala comprising of Emblica officinalis, Terminalia bellerica and Terminalia chebula.

Example-1 Organic Garcinia Tablet Formulation

Experiment- 1 Preparation of Garcinia extract Approximately 100 Kg of shade dried fruit material was subjected to extraction with 400 Liters of purified water by percolation method at room temperature for 24 hours. The water extractions after 24 hours, were filtered through muslin cloth and concentrated to thick paste. After achieving the desired total solid content, the soft extract was spray dried to a free flowing dry extract powder.

Experiment-2 Formula of Granulation

Table No.1

Experiment-3 Formula of Lubrication of granules

Table No.2

Experiment-4 Formula of Tablet preparation

Dispensing of Raw Materials: Dispense the raw materials as per the Batch Formula

Wet Heat Sterilization /Autoclaving: Transfer 15.00 kg of spent powder of Garcinia cambogia (left material after water extraction) and 10 kg of dried fruit powder of Garcinia cambogia into trays and sterilize the material at 121 °C for 30 minutes. Unload the sterilized materials into double lined polybags separately and keep in airtight containers.

Send the sample for LOD and Microbial Analysis and test as per Table No.3 Table No.3

Sift 50.00 kg of water extract of Garcinia cambogia through # 60. Sift 25.00 kg of fruit rind powder of Garcinia cambogia through # 60. Collect the above-sifted materials in separate duly labelled double lined polybags. Record the quantity of sifted materials. Also check the sieve integrity before and after sifting.

Preparation of Granulation Fluid: Transfer about 25 kg of purified water into a clean Stainless Steel Vessel and Record the temperature. Should not exceed 40° C.

Granulation: Load 25.00 kg of powder of Garcinia cambogia into Rapid Mixer Granulator (RMG). Further load 50.00 kg of water extract of fruit of Garcinia cambogia into RMG and blend for about 5 minutes. Slowly add the granulation fluid to the RMG over a period of about 3 minutes with medium speed. Stop the mixer and scrap off the mass from the sides and bottom. Continue mixing by operating the impeller at high speed with chopper ON’ for about 3 minutes. Add additional quantity of purified water, if required, till you get dough like mass (Manual checking). Discharge the mass from the RMG. Record the observations, Record deviations if any. Mill the Wet Mass in Multi mill fitted with 10 mm screen.

Tray Drying: Dry the wet mass in tray drier at about 60°C to 70°C for about four hours. Check the moisture once every hour. (LOD Limit: 4.0 to 5.0% w/w) and record. Sift the dried granules using a Sifter fitted with sieve # 20. Collect the sifted granules in a clean double polythene lined HDPE container. Mill the oversize granules through S.S. Multi Mill fitted with 1.5mm screen with ‘Knives Forward’ direction. Pass the milled granules through a Sifter fitted with # 20 sieve. Collect the sized granules and add them to the sifted granules. Weigh the granules. Record the quantity. Analyze samples as per below Table No.4.If required autoclave the granules at 121 °C for 30 minutes to comply microbial limits. Table No. 4

Blending: Maintain the Temperature and Relative Humidity of the area as per the specified limit (Limit: Temperature NMT 25°C and relative humidity NMT 50%). Transfer the sized granules and fines generated to the blending area. The sized granules and the fines are loaded into Double Cone blender. Blend the ingredients for 3 minutes at 20-25 RPM. Unload the blend in a clean Double polythene lined HDPE drums and affix duly filled status labels. Weigh the blend and record the details. Compression: Maintain the Temperature and Relative Humidity of the compression area within the specified limit (Limit Temperature NMT 25°C and relative humidity NMT 50 %). Check the Temperature and Relative Humidity of the area and record. Bring the drums containing the blend into the compression area. Adjust the Compression machine. Carry out the initial checks before starting the operation as specified in Table No.5.

Table No.5

Check for appearance, average weight and individual weight, thickness, hardness, friability and disintegration of compressed tablets. Check appearance, thickness & hardness of tablets every 30 minutes. Check friability and disintegration time every 30 minutes and record. Check average weight of 20 tablets every 30 minutes and record. Collect the tablets in a double polythene lined, tightly closed, container. Weigh each container and record the details.

Standard Parameters of Tablets: Standard parameters are mentioned in Table No.6.

Table No.6

Collect the compressed tablets in Double polythene lined HDPE drums and record their weights. Affix duly filled status labels to the containers. Packing: Pack 60 tablets in a HDPE, lOOCC container and weigh them for appropriateness of number of tablets.

Raw Material Specification: Organic Garcinia Cambogia Extract.

Table No: 7 Finished Product Specification: Organic Garcinia Cambogia Tablet Table No: 8

FIG. 2 illustrates a high performance liquid chromatography (HPLC) of Garcinia cambogia extract in accordance with example 1 of the present disclosure. Standard Testing Procedure of Assay: Assay of Hydroxy citric Acid (HCA):

Materials required: HPLC grade water, HPLC grade Acetonitrile, Orthophosphoric acid (H3PO4) HPLC grade.

Mobile phase A: 100% Acetonitrile filtered through 0.45pm membrane filter and degassed. Mobile phase B: 0.2% Orthophosphoric acid (H ₃ PO ₄ ) in HPLC water filtered through 0.45pmmembrane filter and degassed.

Gradient Program:

Table No: 9 Column: Kromasil C18, 250 X 4.6mm, 5pm

Flow rate: 1.2 ml per minute Run time: 15 minutes Data acquisition time: 25 minutes Detector wavelength: 210 nm. Injection volume: 20 pi

Diluents: 25% v/v Orthophosphoric acid (H ₃ PO ₄ ) in water

Blank Preparation: Pipette out 5ml of 25% v/v Orthophosphoric acid solution to a 50ml volumetric flask and dilute to volume with HPLC water, mix well.

Standard Preparation: Accurately weigh 50 mg of Calcium salt of Hydroxy citric acid, working standard and transfer to a 50 ml volumetric flask. Dissolve with 5 ml of 25% v/v Orthophosphoric acid. Cool the sample and make up to the volume with HPLC water. Filter through 0.45p Nylon syringe filter or membrane filter. Sample Preparation: Accurately weigh 50 mg of Calcium salt of Hydroxy citric acid and transfer to a 50 ml volumetric flask. Dissolve with 5 ml of 25% v/v Orthophosphoric acid. Cool the sample and make up to the volume with HPLC water. Filter through 0.45m Nylon syringe filter or membrane filter.

Stabilize the instrument with above mobile phase. Inject 20m1 of blank solution followed by 20m1 of the standard solution in triplicate injections. Record the chromatograms. % RSD for area of the triplicate injections of the standard should be NMT 2%. % RSD for the retention time area of the triplicate injections of the standard should be NMT 1%. Inject the sample solution and record the area of the corresponding peak in the chromatogram.

Calculations:

% HCA=Area of HCA peak in the sample X Standard wcight(mg) X 50 X Potency of the std.

Area of HCA peak in the standard X 50 X Sample weight (mg)

Example-2- Organic Bacopa Tablet Formulation

Experiment- 1: Preparation of Bacopa extract

Approximately 100 Kg of shade dried leaves material was subjected to extraction with 400 Litres of ethanol by percolation method at Room Temperature for 24 hours. The ethanol extractions after 24 hours, were filtered through muslin cloth and concentrated to thick paste. After achieving the desired total solid content, the extract was dried to a free flowing dry extract powder.

Experiment -2 Formula of Granulation

Table No.10

Experiment-3 Formula of Lubrication of granules

Table No.il

Experiment-4 Formula of Tablet preparation Dispensing of Raw Materials: Dispense the raw materials as per the Batch Formula.

Wet Heat Sterilization /Autoclaving: Transfer 30kg of spent powder of Bacopa monneiri (left material after extraction) and 20kg of leaf powder of Bacopa monneiri into trays and sterilize the material at 121°C for 30 minutes. Unload the sterilized materials into double lined polybags separately and keep in airtight containers. Send the sample for LOD and Microbial Analysis and test as per Table No.12

Table No.12

Sift 50.00 kg of ethanol extract of Bacopa monneiri through # 60. Sift 50.00 kg of leaves powder of Bacopa monneiri through # 60. Collect the above-sifted materials in separate duly labelled double lined polybags, Record the quantity of sifted materials. Also, check the sieve integrity before and after sifting.

Preparation of Granulation Fluid: Transfer about 25kg of purified water into a clean Stainless Steel Vessel. Record the temperature. Should not exceed 40°C. Granulation: Load 50.00 kg of leaves powder of Bacopa monneiri into Rapid Mixer Granulator (RMG). Further, load 50.00 kg of ethanol extract of leaves of Bacopa monneiri into RMG and blend for about 5 minutes. Slowly add the granulation fluid to the RMG over a period of about 3 minutes with medium speed. Stop the mixer and scrap off the mass from the sides and bottom. Continue mixing by operating the impeller at high speed with chopper ON’ for about 3 minutes. Add additional quantity of purified water, if required, till you get dough like mass. (Manual checking)Discharge the mass from the RMG. Record the observations, Record deviations if any. Mill, the Wet Mass in Multi mill fitted with 10 mm screen.

Tray Drying: Dry the Wet mass in tray Drier at about 60° C to 70° C for about four hours. Check the Moisture once every hour. (LOD Limit: 4.0 to 5.0% w/w) and record. Sift the dried granules using a Sifter fitted with sieve # 20. Collect, the sifted granules in a clean double polythene lined HDPE container. Mill the oversize granules through S.S. Multi Mill fitted with 1.5mm screen with ‘Knives Forward’ direction. Pass the milled granules through a Sifter fitted with # 20 sieve. Collect the sized granules and add them to the sifted granules. Weigh the granules. Record the quantity. Analyze samples as per below Table No.13. If required autoclave the granules at 121°C for 30 minutes to comply microbial limits.

Table No. 13 Blending: Maintain the Temperature and Relative Humidity of the area as per the specified limit (Limit: Temperature NMT 25 °C and relative humidity NMT 50%), Transfer the sized granules and fines generated to the blending area. The sized granules and the fines are loaded into Double Cone blender. Blend the ingredients for 3 minutes at 20-25 RPM. Unload the blend in a clean Double polythene lined HDPE drums and affix duly filled status labels. Weigh the blend and record the details.

Compression: Maintain the Temperature and Relative Humidity of the compression area within the specified limit (Limit Temperature NMT 25 °C and relative humidity NMT 50 %). Check the Temperature and Relative Humidity of the area and record. Bring the drums containing the blend into the compression area. Adjust the Compression machine. Carry out the initial checks before starting the operation as specified in Table No.14.

Table No.14

Check for Appearance, Average Weight and Individual weight, Thickness, Hardness, Friability and Disintegration of compressed tablets. Check appearance, thickness & hardness of tablets every 30 minutes. Check Friability and Disintegration Time every 30 minutes and record. Check Average weight of 20 tablets every 30 minutes and record. Collect the tablets in a double polythene lined, tightly closed, container. Weigh each container and record the details.

Standard Parameters of Tablets Table No.15

Collect the Compressed tablets in Double polythene lined HDPE drums and record their weights. Affix duly filled status labels to the containers. Packing: Pack 60 tablets in a HDPE, 100 CC container and weigh them for appropriateness of number of tablets.

Raw Material Specifications: Organic Bacopa Extract

Table No: 16

Raw Material Specifications: Organic Bacopa powder

Table No: 17

Raw Material Specifications: Organic Bacopa powder

Table No: 18 Finished Product Specification: Organic Bacopa Tablet

Table No: 19

FIG. 3a and 3b illustrates a high performance liquid chromatography (HPLC) of Bacopa monneiri extract in accordance with example 1 of the present disclosure.

Standard Testing Procedure of Assay Estimation of Bacosides by HPLC: Procedure

Mobile Phase A: Dissolve 0.14 g of anhydrous potassium dihydrogen phosphate in 900 ml of water, add 0.5 ml of Phosphoric acid, dilute to 1000 ml with water mix, filter and degas. Mobile Phase B: Acetonitrile, filtered and degassed.

Gradient Programme:

Table No: 20

Chromatographic Conditions:

Column Cl 8, 250 mm X4.6 mm, BDS HYPERSIL Flow rate 1.5 ml per minute Oven temperature 27±1°C Detector UV at 205nm. Injection volume 20 pi

Sample Preparation: Transfer Bacopa extract 100 mg to 100 ml volumetric flask and add 50 ml Methanol. Sonicate, cool to room temperature and Dilute with Methanol and mix. Filter and use for injection.

Standard solution: Transfer about lOOmg of Bacopa Extract RS (Bacoside A3) to 100 ml volumetric flask, add 50 ml of methanol and Sonicate, cool to room temperature and dilute with methanol and mix. Filter and use for injection.

Inject methanol as blank in single, standard solution in triplicate & sample in single and record the chromatograms.

System Suitability: Tailing factor is not more than 1.5 for Bacoside A3 peak in 1 ^st injection of standard solution. % RSD is not more than 2% for Bacoside A3 peak in replicate injections of standard solution.

Relative Retention time & Factors:

Table No: 21

Calculations: Separately calculate the percentages of Bacopaside-I, Bacoside A3, Bacopaside-II, Jujubogenin Isomer of Bacopasaponin C & Bacopasaponin C. Total % of Triterpene Glycosides/ Bacosides = Sum of percentages of all compounds.

% Result (Individual^ Sample area (Individual ^' ) X Standard Concentration X Factor X 100

Standard area of Bacoside A3 peak X Sample Concentration

Example-3- Organic Turmeric Tablet Formulation

Experiment- 1 Preparation of Turmeric extract

Approximately 100 Kg of dried rhizome material was subjected to extraction with 400 Litres of ethanol by percolation method at reflex Temperature for 24 hours. The ethanol extractions after 24 hours, were filtered through muslin cloth and concentrated to oleoresin. Oleoresin was kept for crystallization with ethanol.

Experiment -2 Formula of Granulation

Table No.22

Experiment-3 Formula of Lubrication of Granules

Table No.23 Experiment-4 Formula of Tablet preparation

Dispensing of Raw Materials: Dispense the raw materials as per the Batch Formula.

Wet Heat Sterilization /Autoclaving: Transfer 30.00 kg of spent powder of Curcuma longa (left material after water extraction) and 20 kg of rhizome powder of Curcuma longa into trays and sterilize the material at 121°C for 30 minutes. Unload the sterilized materials into double lined polybags separately and keep in airtight containers. Send, the sample for LOD and Microbial Analysis and test as per Table No.24.

Table No.24

Sift 25.00 kg of water extract of Curcuma longa through # 60. Sift 25.00 kg of rhizome powder of Curcuma longa through # 60. Collect, the above-sifted materials in separate duly labelled double lined polybags, Record the quantity of sifted materials. Also, check the sieve integrity before and after sifting.

Preparation of Granulation Fluid: Transfer about 25 kg of purified water into a clean Stainless Steel Vessel. Record the temperature. Should not exceed 40°C.

Granulation: Load 50.00 kg of rhizome powder of Curcuma longa into Rapid Mixer Granulator (RMG). Further, load 50.00 kg of ethanol extract of rhizome of Curcuma longa into RMG and blend for about 5 minutes. Slowly add the granulation fluid to the RMG over a period of about 3 minutes with medium speed. Stop the mixer and scrap off the mass from the sides and bottom. Continue mixing by operating the impeller at high speed with chopper ON’ for about 3 minutes. Add additional quantity of purified water, if required, till you get dough like mass (Manual checking). Discharge the mass from the RMG. Record the observations, Record deviations if any. Mill the Wet Mass in Multi mill fitted with 10 mm screen. Tray Drying: Dry the Wet mass in tray Drier at about 60°C to 70°C for about four hours. Check the Moisture once every hour. (LOD Limit: 4.0 to 5.0% w/w) and record. Sift the dried granules using a Sifter fitted with sieve # 20. Collect, the sifted granules in a clean double polythene lined HDPE container. Mill the oversize granules through S.S. Multi Mill fitted with 1.5mm screen with ‘Knives Forward’ direction. Pass the milled granules through a Sifter fitted with #20 sieve. Collect the sized granules and add them to the sifted granules. Weigh the granules. Record the quantity. Analyze samples as per below Table No.25. If required autoclave the granules at 121°C for 30 minutes to comply microbial limits.

Table No. 25

Blending: Maintain the Temperature and Relative Humidity of the area as per the specified limit (Limit: Temperature NMT 25°C and relative humidity NMT 50%) . Transfer the sized granules and fines generated to the blending area. The sized granules and the fines are loaded into Double Cone blender. Blend the ingredients for 3 minutes at 20-25 RPM. Unload the blend in a clean Double polythene lined HDPE drums and affix duly filled status labels. Weigh the blend and record the details.

Compression: Maintain the Temperature and Relative Humidity of the compression area within the specified limit (Limit Temperature NMT 25°C and relative humidity NMT 50 %). Check the Temperature and Relative Humidity of the area and record. Bring the drums containing the blend into the compression area. Adjust the Compression machine. Carry out the initial checks before starting the operation as specified in Table No.26.

Table No.26

Check for Appearance, Average Weight and Individual weight, Thickness, Hardness, Friability and Disintegration of compressed tablets. Check appearance, thickness & hardness of tablets every 30 minutes. Check Friability and Disintegration Time every 30 minutes and record. Check Average weight of 20 tablets every 30 minutes and record. Collect the tablets in a double polythene lined, tightly closed, container. Weigh each container and record the details.

Standard Parameters of Tablets Table No.27

Collect the Compressed tablets in Double polythene lined HDPE drums and record their weights. Affix, duly filled status labels to the containers. Packing: Pack 60 tablets in a HDPE, 100 CC container and weigh them for appropriateness of number of tablets. Raw Material Specifications: Organic Turmeric Extract

Table No: 28

Table No: 29

Raw Material Specifications: Organic Turmeric Powder

Table No: 30

Finished Product Specification: Organic Turmeric Tablet

Table No: 31

FIG. 4 illustrates a high performance liquid chromatography (HPLC)of Curcuma longa extract in accordance with example 1 of the present disclosure.

Standard Testing Procedure of Assay Estimation of Curcuminoids by HPLC: Procedure

Sample preparation: Determine the average weight from NLT 20 tablets. Crush the tablets to fine uniform powder. Prepare, a concentration of 0.1 mg/ml of the sample in Methanol.

Standard preparation: Prepare a concentration of 0.1 mg/ml of the standard in Methanol. Chromatographic Conditions:

Column: Kromasil Cl 8, 250 X 4.6mm, 5 micron Flow rate: l.OmL/min Wavelength: 425nm

Mobile phase: Acetonitrile: Water: Acetic acid: Methanol (50:50:1:5) Diluent: Methanol, HPLC grade.

Stabilize the instrument with above mobile phase. Inject 20pl of the standard solution and record the chromatogram. The percentage RSD for the area for peaks of Curcumin, Demethoxycurcumin and Bisdemethoxycurcumin should be less than 2.0% for triplicate consecutive injections. Inject the sample solution and record the area of the corresponding peaks in the chromatogram.

Approximate Retention times of Bisdemethoxy Curcumin is 9.8 minutes, Demethoxy Curcumin is 10.6 minutes and Curcumin is 11.7 minutes. Calculation:

% Turmeric extract =

Total Spl. area of PMC, BDMC, Curcumin X Std. Cone. X Pot. Of Curcumin Total Standard area of DMC, BDMC, Curcumin X Sample Cone.

Turmeric extract in mg/tablet = % Turmeric extract X Average wtXlOO

100X40

Wherein BDMC is BisdemethoxyCurcumin and DMC is Demethoxy Curcumin .

Example-4 - Organic Moringa Tablet Formulation

Approximately 100 Kg of shade dried leaves material was subjected to extraction with 400 Litres of purified water by percolation method at Room Temperature for 24 hours. The water extractions after 24 hours, were filtered through muslin cloth and concentrated to thick paste. After achieving the desired total solid content, the soft extract was spray dried to a free flowing dry extract powder.

Experiment -2 Formula of Granulation

Table No.32

Experiment-3Formula of Lubrication of granules

Table No.33

Experiment -4 Formula of Tablet preparation

Dispensing of Raw Materials: Dispense the raw materials as per the Batch Formula.

Wet Heat Sterilization /Autoclaving: Transfer 30.00 kg of spent powder of Moringa oliefera{ left material after water extraction) and 20 kg of leaf powder of Moringa oliefera into trays and sterilize the material at 121 °C for 30 minutes. Unload the sterilized materials into double lined polybags separately and keep in airtight containers. Send the sample for FOD and Microbial Analysis and test as per Table No.34

Table No.34

Sift 10.00 kg of water extract of Moringa oleifera through # 60. Sift 50.00 kg of leaves powder of Moringa oleifera through # 60.Collect the above-sifted materials in separate duly labelled double lined polybags, Record the quantity of sifted materials. Also, check the sieve integrity before and after sifting.

Preparation of Granulation Fluid: Transfer about 25 kg of purified water into a clean Stainless Steel Vessel and Record the temperature. Should not exceed 40° C. Granulation: Foad 50.00 kg of leaves powder of Moringa oleifera into Rapid Mixer Granulator (RMG). Further load 10.00 kg of water extract of leaves of Moringa oleifera into RMG and blend for about 5 minutes. Slowly add the granulation fluid to the RMG over a period of about 3 minutes with medium speed. Stop the mixer and scrap off the mass from the sides and bottom. Continue mixing by operating the impeller at high speed with chopper ON’ for about 3 minutes. Add additional quantity of purified water, if required, till you get dough like mass (Manual checking). Discharge the mass from the RMG. Record the observations, Record deviations if any. Mill the Wet Mass in Multi mill fitted with 10 mm screen.

Tray Drying: Dry the Wet mass in tray Drier at about 60° C to 70° C for about four hours. Check the Moisture once every hour. (LOD Limit: 4.0 to 5.0% w/w) and record. Sift the dried granules using a Sifter fitted with sieve # 20. Collect the sifted granules in a clean double polythene lined HDPE container. Mill the oversize granules through S.S. Multi Mill fitted with 1.5mm screen with ‘Knives Forward’ direction. Pass the milled granules through a Sifter fitted with # 20 sieve. Collect the sized granules and add them to the sifted granules. Weigh the granules. Record the quantity. Analyze samples as per below Table No.35. If required autoclave the granules at 121 °C for 30 minutes to comply microbial limits.

Table No. 35

Blending: Maintain the Temperature and Relative Humidity of the area as per the specified limit (Limit: Temperature NMT 25 °C and relative humidity NMT 50%). Transfer the sized granules and fines generated to the blending area. The sized granules and the fines are loaded into Double Cone blender. Blend the ingredients for 3 minutes at 20-25 RPM. Unload the blend in a clean Double polythene lined HDPE drums and affix duly filled status labels. Weigh the blend and record the details.

Compression: Maintain the Temperature and Relative Humidity of the compression area within the specified limit (Limit Temperature NMT 25 °C and relative humidity NMT 50 %). Check the Temperature and Relative Humidity of the area and record. Bring the drums containing the blend into the compression area. Adjust the Compression machine. Carry out the initial checks before starting the operation as specified in Table No.36.

Table No.36

Check for Appearance, Average Weight and Individual weight, Thickness, Hardness, Friability and Disintegration of compressed tablets. Check appearance, thickness & hardness of tablets every 30 minutes. Check Friability and Disintegration Time every 30 minutes and record. Check Average weight of 20 tablets every 30 minutes and record. Collect the tablets in a double polythene lined, tightly closed, container. Weigh each container and record the details. Standard Parameters of Tablets

Table No.37

Collect the Compressed tablets in Double polythene lined HDPE drums and record their weights. Affix duly filled status labels to the containers. Packing: Pack 60 tablets in a HDPE, 100 CC container and weigh them for appropriateness of number of tablets.

Raw Materials Specification: Organic Moringa Extract Table No: 38

Table No: 39 Raw Materials Specification: Organic Moringa Powder

Table No: 40

Finished Product Specification: Organic Moringa Tablet

Table No: 41

S tandard Testing Procedure of Assay

Estimation of Assay of Saponins by Gravimetry: Procedure

Weigh about 1-5 g of the sample as per the criteria mentioned below.

Weight of the sample to be taken for the analysis:

Table No: 42

If the sample is a thick paste, add about 10 ml of water to the weighed sample, sonicate to obtain thin slurry and proceed for the analysis. If the sample is a crude drug, ensure that it is finely powdered before weighing. Extract with 90% methanol (25ml) by refluxing for half an hour at 70-80°C. Extract the residue few more times by taking 25 ml of 90% methanol till the extracts are almost colourless. Combine Methanolic extracts and evaporate the solvent on water bath followed by drying in oven for 2hrs. Treat the obtained extracts with 25 ml of pet. Ether (60-80°C) reflux for half an hour at 60°C. Cool and remove the solvent by decantation and discard. Similarly extract the residue with 25 ml chloroform and 25 ml ethyl acetate. Dissolve the residue left in 5ml of 100% methanol. Add the above drop by drop with constant stirring to 25 ml acetone to precipitate saponins. Use an increment of 25 ml Acetone for every 5 ml of 100% methanol added. Stand Overnight to settle. Evaporate the acetone completely on water bath below 60°C, and dry the precipitate to constant weigh at 105°C.

Calculation:

% Total Saponins = Wt of the residue (in g) x 100

Wt of the sample taken (in g) Example-5 - Organic Triphala Tablet Formulation

Experiment- 1: Preparation of Triphala extract

Approximately 100 Kg of shade dried fruit material was subjected to extraction with 400 Litres of purified water by percolation method at Room Temperature for 24 hours. The water extractions after 24 hours, were filtered through muslin cloth and concentrated to thick paste. After achieving the desired total solid content, the soft extract was spray dried to a free flowing dry extract powder. Experiment -2 Formula of Granulation

Table No.43 Experiment -3Formula of Lubrication of granules

Table No.44 Experiment -4 Formula of Tablet preparation

Dispensing of Raw Materials: Dispense the raw materials as per the Batch Formula.

Wet Heat Sterilization /Autoclaving: Transfer 15.00 kg of spent powder of Triphala Fruit (left material after water extraction) and 5 kg of fruit powder of Triphala into trays and sterilize the material at 121 °C for 30 minutes. Unload the sterilized materials into double lined polybags separately and keep in airtight containers. Send the sample for LOD and Microbial Analysis and test as per Table No.45 Table No.45 Sift 40.00 kg of water extract of Triphala through # 60. Sift 20.00 kg powder of Triphala through # 60. Collect the above-sifted materials in separate duly labelled double lined polybags, Record the quantity of sifted materials. Also check the sieve integrity before and after sifting. Preparation of Granulation Fluid: Transfer about 25 kg of purified water into a clean Stainless Steel Vessel. Record the temperature. Should not exceed 40° C.

Granulation: Load 20.00 kg of powder of Triphala into Rapid Mixer Granulator (RMG). Further load 40.00 kg of water extract of fruit of Triphala into RMG and blend for about 5 minutes. Slowly add the granulation fluid to the RMG over a period of about 3 minutes with medium speed. Stop the mixer and scrap off the mass from the sides and bottom. Continue mixing by operating the impeller at high speed with chopper ON’ for about 3 minutes. Add additional quantity of purified water, if required, till you get dough like mass (Manual checking). Discharge the mass from the RMG. Record the observations, Record deviations if any. Mill the Wet Mass in Multi mill fitted with 10 mm screen.

Tray Drying: Dry the Wet mass in tray Drier at about 60° C to 70° C for about four hours. Check the Moisture once every hour. (LOD Limit: 4.0 to 5.0% w/w) and record. Sift the dried granules using a Sifter fitted with sieve # 20. Collect the sifted granules in a clean double polythene lined HD PE container. Mill the oversize granules through S.S. Multi Mill fitted with 1.5mm screen with ‘Knives Forward’ direction. Pass the milled granules through a Sifter fitted with # 20 sieve. Collect the sized granules and add them to the sifted granules. Weigh the granules. Record the quantity. Analyze samples as per below Table No.46. If required autoclave the granules at 121 °C for 30 minutes to comply microbial limits.

Table No. 46

Blending: Maintain the Temperature and Relative Humidity of the area as per the specified limit (Limit: Temperature NMT 25°C and relative humidity NMT 50%. Transfer the sized granules and fines generated to the blending area. The sized granules and the fines are loaded into Double Cone blender. Blend the ingredients for 3 minutes at 20-25 RPM. Unload the blend in a clean Double polythene lined HDPE drums and affix duly filled status labels. Weigh the blend and record the details.

Compression: Maintain the Temperature and Relative Humidity of the compression area within the specified limit (Fimit Temperature NMT 25 °C and relative humidity NMT 50 %). Check the Temperature and Relative Humidity of the area and record. Bring the drums containing the blend into the compression area. Adjust the Compression machine. Carry out the initial checks before starting the operation as specified in Table No.47.

Table No.47

Check for Appearance, Average Weight and Individual weight, Thickness, Hardness, Friability and Disintegration of compressed tablets. Check appearance, thickness & hardness of tablets every 30 minutes. Check Friability and Disintegration Time every 30 minutes and record. Check Average weight of 20 tablets every 30 minutes and record. Collect the tablets in a double polythene lined, tightly closed, container. Weigh each container and record the details.

Standard Parameters of Tablets

Table No.48

Collect the Compressed tablets in Double polythene lined HDPE drums and record their weights. Affix duly filled status labels to the containers. Packing: Pack 60 tablets in a HDPE, 100 CC container and weigh them for appropriateness of number of tablets.

Raw Material Specification: Organic Triphala Extract

Table No: 49 Table No: 50

Raw Material Specification: Organic Triphala Powder

Table No: 51

Finished Product Specification: Organic Triphala Tablet

Table No: 52

Standard Testing Procedure of Assay

Estimation of Assay of Tannins by Titrimetry: Procedure:

Reagents and chemicals: Potassium permanganate 0.1 N: Dissolve 3.2 g of KMn04 in 500 ml of Distilled water. Make up the volume to 1000 ml. Heat on water bath for 1.0 hr. Cool and allow standing for one day. Filter the solution and transfer to reagent bottle.

Sulphuric acid 1:3: Add 25 ml of cone sulphuric acid to 75 ml distilled water.

Indigo sulfonic acid solution: Take 1.0 g of Indigo Carmine in a 250 ml conical flask. Add 25 ml Cone. Sulphuric acid and mix well. Transfer this slowly to a 1000ml volumetric flask already containing 500 ml of dist. water with constant stirring. To the flask add another 25 ml of cone. Sulphuric acid to rinse and slowly transfer to the volumetric flask. Make up the volume to 1000 ml to get 0.1% Indigo Sulfonic acid solution.

Standardization of 0.1 N KMn04 solution: Accurately weigh 0.3 g of sodium oxalate. To this add 200 ml of water and 25 ml of Sulphuric acid (1:3). Titrate with 0.1 N Potassium permanganate solution till colour changes from Colourless to Pink.

Normality of the solution = weight of sample x 2 xlOOO

Burette Reading x 134

Preparation of sample: Accurately weigh 0.2 g of Sample. Dissolve in 50 ml water. Add 250 ml of water and mix well. Do not filter the solution. To, this add 25 ml Indigo sulfonic acid and mix well. Titrate this against 0.1 N KMn04 solution till golden yellow colour develops. Note, the burette reading (S). Take, a blank reading without sample (B). Note: 1 ml of 0.1 N KMnCC is equivalent to 0.004157 g of tannin.

Calculation:

% Tannin = (S-B) x 0.004157 x Actual Molarity of 0.1 N KMn04 x 100

0.1 x weight of sample

Overall, the present invention provides a method for preparation of an organic formulation without use of any pharmaceutical excipients and also exhibits improved properties which makes it a viable alternative for formulations containing chemical pharmaceutical excipients. While specific language has been used to describe the disclosure, any limitations arising on account of the same are not intended. As would be apparent to a person skilled in the art, various working modifications may be made to the method in order to implement the inventive concept as taught herein.

The figures and the foregoing description give examples of embodiments. Those skilled in the art will appreciate that one or more of the described elements may well be combined into a single functional element. Alternatively, certain elements may be split into multiple functional elements. Elements from one embodiment may be added to another embodiment. For example, order of processes described herein may be changed and are not limited to the manner described herein. Moreover, the actions of any flow diagram need not be implemented in the order shown; nor do all of the acts need to be necessarily performed. Also, those acts that are not dependant on other acts may be performed in parallel with the other acts. The scope of embodiments is by no means limited by these specific examples.