DESC:FIELD OF THE INVENTION

The present invention relates to oral veterinary compositions comprising nutritional components such as calcium, phosphorus and vitamins for the treatment and/or maintenance of animal health. Further the invention relates to the process for preparation of the said compositions.

BACKGROUND OF THE INVENTION

The nutritional components such as calcium, phosphorus and vitamins are involved in a number of physiological functions important for the animal body. Ruminants and other domestic animals generally depend on dietary sources for their daily requirements.

Several compositions containing calcium-vitamin sources are available as veterinary compositions. However, such compositions available today still present a number of problems which render them not altogether acceptable. The marketed product, CALSHAKTI® (by Intas Pharmaceuticals Limited) is available as a ready-made suspension comprising vitamin-calcium sources, but it involves difficulties in the preparation of ready-made suspension resulting into excess of water wastage and also problems of transportation of large bottles filled with liquid dosage form.

The present invention overcomes these problems by making an oral veterinary composition comprising granules of calcium, phosphorous and vitamins. The said granules can be easily reconstituted as a suspension dosage form.

Further, the present invention successfully overcomes the problem associated with the prior art compositions, in particular:
a) the homogenous distribution of Vitamin D3 in the final product;
b) the flow properties of the said composition;
c) the rate of reconstitution of the suspension to be prepared, as and when required;
d) stability of suspension after reconstitution.

Thus the present invention is advantageous to provide a stable oral veterinary composition comprising nutritional components such as Calcium, Phosphorus and Vitamins. Such compositions preserve good stability and nutritional value to the animal health.

OBJECTS OF THE INVENTION

The primary object of the invention is to provide an oral veterinary composition comprising solid granules of nutritional components that can be easily reconstituted as a suspension dosage form.

Another object of the invention is to provide an oral veterinary composition comprising solid granules of tricalcium phosphate, vitamin D3 and vitamin B12 with suitable excipients, wherein the granules can be easily reconstituted as a suspension dosage form.

Another object of the invention is to provide an oral veterinary composition comprising solid granules of tricalcium phosphate, vitamin D3 and vitamin B12 with suitable excipients, wherein the reconstituted suspension prepared from the said granules is stable for at least two months after reconstitution.

Another object of the invention is to provide an oral veterinary composition comprising solid granules of tricalcium phosphate, vitamin D3 and vitamin B12 with suitable excipients, wherein the vitamin D3 is homogenously distributed in the final product.

Another object of the invention is to provide a process for the preparation of an oral veterinary composition comprising solid granules of tricalcium phosphate, vitamin D3 and vitamin B12 with suitable excipients.

SUMMARY OF THE INVENTION

In a first embodiment, the invention relates to an oral veterinary composition comprising solid granules of tricalcium phosphate, vitamin D3 and vitamin B12 with suitable excipients, wherein the granules can be easily reconstituted as a suspension dosage form.

In a preferred embodiment, the invention relates to an oral veterinary composition comprising solid granules of tricalcium phosphate, vitamin D3 and vitamin B12 with suitable excipients, wherein the reconstituted suspension is stable for at least two months after reconstitution.

In a preferred embodiment, the invention relates to an oral veterinary composition comprising solid granules of tricalcium phosphate, oil-soluble vitamin D3, water-soluble vitamin B12, optionally with herbal extracts, wherein the granules can be easily reconstituted as a suspension dosage form.

In another embodiment, the invention relates to an oral veterinary composition comprising solid granules of tricalcium phosphate, vitamin D3 and vitamin B12 with suitable excipients, wherein the vitamin D3 is homogenously distributed in the final product.

In another embodiment, the invention relates to a process for the preparation of an oral veterinary composition comprising solid granules of tricalcium phosphate, vitamin D3 and vitamin B12 with suitable excipients, wherein the said granulation process involves rapid mixer granulator.

DETAILED DESCRIPTION

The present invention relates to an oral veterinary composition comprising solid granules of tricalcium phosphate, vitamin D3 and vitamin B12 with suitable excipients, wherein the granules can be easily reconstituted as a suspension dosage form.

The present invention is advantageous to overcome the problems of the prior art compositions, in particular:
a) the homogenous distribution of Vitamin D3 in the final product;
b) the flow properties of the said granular composition;
c) the rate of reconstitution of the suspension to be prepared, as and when required;
d) stability of suspension after reconstitution.

The present invention provides a homogenous mixture of tricalcium phosphate with oil-soluble vitamin D3 and water-soluble vitamin B12. The granular composition exhibit good flowability for ease of reconstitution and the final suspension is stable for at least two months after reconstitution.

The vitamin D3 is available in crystal form and exhibit stability at 2-8 °C. Since it is an oil-soluble component, it provides difficulty in solubilization and homogenous distribution in the final product. However, the inventors of the present invention have successfully dissolved vitamin D3 in an aqueous solution containing Polysorbate, preferably Polysorbate 80. The vitamin D3 exists in a micellar form in the aqueous solution and thereby it provides homogenous distribution in the final product. The vitamin B12 solution phase can be mixed with the solution phase of vitamin D3 with stirring.

The oral veterinary compositions of the present invention may optionally contain herbal extracts such as shatavari, jivantri, piper longum and the like.

The oral veterinary compositions of the present invention comprise solid granules of tricalcium phosphate, vitamin D3 and vitamin B12 with suitable excipients. For the purpose of this invention, the suitable excipients can be selected from the group of diluents, binders, disintegrants, lubricant, glidants, wetting agents, surfactants, suspending agents, sweetening agents, flavoring agents, coloring agents, viscosity-builders, flocculating agents, buffers, solubilizers, pH-adjusting agents, chelating agents, preservatives, inorganic and organic salts, solvents and the like.

In a preferred embodiment, the suitable excipients includes, non-limiting examples, such as sucrose, xanthan gum, sodium saccharine, Polysorbate 80, methyl paraben sodium, propyl paraben sodium, ascorbic acid, colloidal anhydrous silica, flavors, herbal extracts, citric acid, sodium citrate, butylated hydroxy anisole and purified water.

The granular compositions of the present invention can be easily reconstituted as a suspension that is stable for at least two months after reconstitution.

The granular compositions of the present invention preserve microbial and physical stability of the reconstituted suspension.

The granular compositions of the present invention exhibit good flow properties and it can be easily dispensed through hopper to fill into sachets or packets.

In another embodiment, the invention relates to a process for the preparation of an oral veterinary composition comprising solid granules of tricalcium phosphate, vitamin D3 and vitamin B12 with suitable excipients. The process for the preparation of the said composition comprises steps of sifting, mixing, granulation, milling, drying, blending, lubrication and filling. Preferably, the granulation process involves rapid mixer granulator (RMG).

In order to further illustrate the present invention, the following examples are provided for the purpose of clarity of understanding. However, it is not intended in any way to limit the scope of present invention and it is readily apparent to those of ordinary skill in the art in light of the teachings of this invention that certain changes and modifications may be made thereto without departing from the scope of the invention.

Example 1: Oral Veterinary Composition.
Each 100 ml reconstituted suspension contains:
Calcium ………………... 1700 to 3500 mg
Phosphorus …………….. 850 to 1750 mg
Vitamin D3 IP …………. 8000 IU to 16000 IU
Vitamin B12 IP………… 100 mcg to 200 mcg

No. Ingredients Qty (%w/w)
1. Tricalcium Phosphate ** 10 to 35
2. Sucrose1 (Granular) 20 to 70
3. Xanthan Gum ** 0.3 to 2.0
4. Sodium Saccharine ** 0.1 to 0.5
5. Polysorbate 80 0.05 to 0.2
6. Methyl Paraben Sodium 0.2 to 1.0
7. Propyl Paraben Sodium 0.02 to 0.1
8. Vitamin D3 0.0010 to 0.0050
9. Vitamin B12 0.0005 to 0.0020
10. Ascorbic Acid 0.05 to 0.25
11. Colloidal Anhydrous Silica 0.2 to 1.0
12. Mango Flavor ** 0.2 to 2.0
13. Erythrosine supra 0.01 to 0.1
14. Anhydrous Citric acid ** 0.5 to 3.0
15. Sodium citrate ** 0.5 to 3.0
16. Sodium Benzoate ** 0.5 to 3.0
17. Extract of Shatavari (4:1) ** 0.2 to 3.0
18. Extract of Jivanti (10:1) ** 0.2 to 3.0
19. Extract of Piper Longum (Lindi Piper) (4:1) ** 0.1 to 0.5
20. Butylated Hydroxy Anisole 0.01 to 0.05
21 Purified water2 2 to 152

** Fine materials having particle size less than 600 micron.
1: Sucrose: Granular grade with Particle size: NMT 10% retains on 40# (425 micron) & NMT 10 % passes through 80# (180 micron)
2. Purified water: Used in granulation process. Removed in drying step & only trace amount may present in final product.

Manufacturing Process:
(i) Co-sift the ingredients Tricalcium Phosphate, Sucrose, Sodium Saccharine, Methyl Paraben Sodium, Propyl Paraben Sodium, Anhydrous Citric acid, Sodium citrate, Sodium Benzoate, Extract of Shatavari, Extract of Jivanti, Extract of Piper Longum. Mix all the ingredients into Rapid Mixer Granulator (RMG).
(ii) Prepare a solution phase by adding Butylated Hydroxy Anisole in Polysorbate 80. Add Vitamin D3 into this solution and stir to dissolve it completely.
(iii) Add Vitamin B12 solution phase of the solution phase of Vitamin D3 phase with stirring.
(iv) Granulate the mixed ingredients in RMG with solution of step (iii).
(v) The wet granules are subjected to wet milling and subsequent drying.
(vi) Sift the dried granules and pass through the milling step.
(vii) The milled granules are blended and with lubricant and flavoring agents.
(viii) The granules obtained are filled in bags/sachets/bottles

Example 2: Oral Veterinary Composition.
No. Ingredients Overages (%) Quantity
(gm / 33 gm granules)
1. Tricalcium Phosphate 6 9.561
2. Sucrose (40-80#) - 20.0
3. Saccharin Sodium (Micronized-180 micron) - 0.10
4. Methyl Paraben Sodium - 0.20
5. Propyl Paraben Sodium - 0.02
6. Sodium Benzoate - 0.50
7. Anhydrous Citric acid - 0.495
8. Sodium citrate - 0.420
9. Erythrosine supra - 12.0 mg
10. Extract of Shatavari (4:1) - 0.30
11. Extract of Jivanti (10:1) - 0.30
12. Extract of Piper Longum (Lindi Piper) (4:1) - 0.12
13. Anhydrous Citric acid - 5.0 mg
14. Sodium citrate - 0.08
15. Ascorbic Acid - 0.05
16. Purified water - 1.64*
17. Vitamin B12 100 0.402 mg
18. Butylated Hydroxy Anisole - 0.01
19. Polysorbate 80 - 0.07
20. Vitamin D3 200 1.203 mg
21. Xanthan Gum - 0.30
22. Powdarome Mango Premium - 0.16
23. Colloidal Anhydrous Silica - 0.20

1 Including 6 % overages and mentioned quantity is considering assay as 100 % on as is basis, Potency correction to be done while dispensing considering the actual assay on as is basis.
2 Including 100 % overages and mentioned quantity is considering assay as 100 % on as is basis, Potency correction to be done while dispensing considering the actual assay on as is basis.
3 Including 200 % overages and mentioned quantity is considering assay as 100 % on as is basis, Potency correction to be done while dispensing considering the actual assay on as is basis.
* Remain in traces, Lost during processing.

The Example 2 can be prepared by the same procedure as described for Example 1.

Stability data of Oral Veterinary Composition:
Each 33 gm Powder contains:
Calcium ………………... 3500 mg
Phosphorus ……………. 1750 mg
Vitamin D3 IP ………… 16000 IU
Vitamin B12 IP………… 200 mcg

Test Conditions Initial 40 °C/75% RH – 3 months 30 °C/65% RH – 3 months 25 °C/60% RH – 3 months
Description Pink coloured Granular powder Pink coloured Granular powder Pink coloured Granular powder Pink coloured Granular powder
pH* 4.79 4.96 5.03 5.03
Assay Measurement Set-1 Set-2 Set-1 Set-2 Set-1 Set-2 Set-1 Set-2
Assay of Calcium 98.8 99.2 99.1 99.0 99.1 99.2 99.2 99.1
Assay of Phosphorus 100.5 101.0 100.0 99.1 99.1 99.8 99.9 99.1
Assay of Vitamin D3 287.5 263.6 112.1 113.0 203.5 204.7 231.9 233.8
Assay of Vitamin B12 181.8 179.0 134. 2 136.8 161.2 162.2 162.8 165.0
* pH of suspension (Each 33 gm Powder after dilution to 100 ml).
Set-1 and Set-2 are two sets of observations.

The above stability data confirms that the Oral Veterinary Composition is stable for at least two months after reconstitution.
,CLAIMS:1. An oral veterinary composition comprising solid granules of tricalcium phosphate, vitamin D3 and vitamin B12 with suitable excipients.

2. The oral veterinary composition according to claim 1, wherein the granules can be easily reconstituted as a suspension dosage form.

3. The oral veterinary composition according to claim 2, wherein the reconstituted suspension is stable for at least two months after reconstitution.

4. The oral veterinary composition according to claim 1, wherein the granules comprise a homogenous mixture of tricalcium phosphate with oil-soluble vitamin D3 and water-soluble vitamin B12.

5. The oral veterinary composition according to claim 1, wherein the granules comprise Polysorbate 80.

6. The oral veterinary composition according to claim 1, wherein the granules optionally comprise of herbal extracts selected from shatavari, jivantri and piper longum.

7. An oral veterinary composition comprising solid granules, wherein the granules comprise a homogenous mixture of tricalcium phosphate with oil-soluble vitamin D3 and water-soluble vitamin B12, with suitable excipients.

8. The oral veterinary composition according to claim 7, wherein the granules can be easily reconstituted as a suspension dosage form.

9. A process for preparation of an oral veterinary composition comprising solid granules of tricalcium phosphate, vitamin D3 and vitamin B12 with suitable excipients, wherein the process comprises steps of sifting, mixing, granulation, milling, drying, blending, lubrication and filling.

10. The process for preparation of veterinary composition according to claim 9, wherein the said process involves rapid mixer granulator.