ORALLY DISPERSIBLE COMPOUND CONTAINING AN ESTER OR SALT OF N-BUTYRIC ACID AND PROCESS FOR PRODUCTION

Abstract

An orally dispersible compound, which contains at least one ester or a salt of n-butyric acid, includes a granular material including at least one ester or salt of n-butyric acid and having a first and a second coating, and at least one excipient which is capable of making the granular material orally dispersible. The first coating includes from 20.0% to 99.0% by weight with respect to the first coating of saturated fatty acids with a C.sub.14-C.sub.22 long chain, and the second coating includes at least one thickening agent, the first coating being between the granular material and the second coating.

Claims

1. An orally dispersible compound, which contains at least one ester or a salt of n-butyric acid, comprising: a granular material comprising the at least one ester or salt of n-butyric acid and having a first and a second coating, and at least one excipient which is arranged on the surface of the granular material and which is dissolvable in the oral cavity within a maximum time of 3 minutes and which is capable of making the granular material orally dispersible, the first coating comprising from 20.0% to 99.0% by weight with respect to the first coating of saturated fatty acids with a C.sub.14-C.sub.22 long chain, and the second coating comprising at least one thickening agent, the first coating being between the granular material and the second coating.

2. The orally dispersible compound according to claim 1, wherein the at least one thickening agent of the second coating is selected from the group consisting of: rubbers, alginates, starches, modified starches, flours, algae, products derived from algae, polyols and polysaccharides.

3. The orally dispersible compound according to claim 2, wherein the at least one thickening agent comprises guar gum, corn starch and sorbitol.

4. The orally dispersible compound according to claim 3, wherein the at least one thickening agent comprises from 0.5% to 10.0% by weight of guar gum, from 30.0% to 90.0% by weight of corn starch and from 10.0% to 60.0% by weight of sorbitol.

5. The orally dispersible compound according to claim 1, wherein the at least one excipient which is capable of making the granular material orally dispersible comprises isomalt and guar gum.

6. The orally dispersible compound according to claim 2, wherein the at least one thickening agent of the second coating comprises sodium alginate.

7. The orally dispersible compound according to claim 1, wherein the first coating comprises from 0.5% to 20.0% by weight of a mineral filler.

8. The orally dispersible compound according to claim 7, wherein the mineral filler comprises between 0.2% and 5.0% by weight of calcium sulphate dihydrate with respect to the first coating.

9. The orally dispersible compound according to claim 1, wherein the at least one excipient which is capable of making the granular material orally dispersible comprises: from 30.0% to 90.0% by weight of isomalt, with respect to the orally dispersible compound, and from 0.1% to 10.0% by weight, of guar gum with respect to the orally dispersible compound.

10. A process for preparing an orally dispersible compound according to claim 1 comprising: providing a granular material comprising the at least one ester or salt of n-butyric acid having a first coating comprising from 20.0% to 99.0% by weight with respect to the first coating of saturated fatty acids with a C.sub.14-C.sub.22 long chain; recoating the granular material having the first coating with a second coating comprising at least one thickening agent; granulating the granular material comprising the first coating and the second coating with at least one excipient which is dissolvable in the oral cavity within a maximum time of 3 minutes and which is capable of making the granular material orally dispersible.

11. The process for preparing an orally dispersible compound according to claim 10, further comprising: providing a granular material comprising the at least one ester or salt of n-butyric acid having a first coating comprising from 20.0% to 99.0% by weight with respect to the first coating of saturated fatty acids with a long C.sub.14-C.sub.22 chain; recoating the granular material having the first coating with a second coating comprising guar gum, corn starch and sorbitol; granulating the granular material having the first coating and the second coating with isomalt and guar gum.

12. The process for preparing an orally dispersible compound according to claim 10, wherein the step of recoating the granular material having the first coating with the second coating is carried out in a fluid-bed granulator.

13. The process for preparing an orally dispersible compound according to claim 10, wherein the granulation is carried out in a fluid-bed granulator.

Description

EMBODIMENTS

First Coating

[0086] In a first example, the first coating was prepared in accordance with EP2352386 A1.

[0087] The composition of the granular material having a first coating in accordance with this example is set out in Table 1.

TABLE-US-00001 TABLE 1 Composition of the granular material having a first coating Component % by weight Granular material Sodium butyrate 50.8 First coating Saturated fatty acids C.sub.14-C.sub.22 45.5 Calcium carbonate 2.5 Calcium stearate 0.5 Calcium sulphate dihydrate 0.5 Flavouring 0.2

Second Coating

Preparation of the First Aqueous Solution A

[0088] There were mixed at ambient temperature water and guar gum at concentrations of 0.6% by weight with respect to the total of the solution. Subsequently, this mixture was brought to 80 C. and 0.6% by weight of sodium alginate with respect to the total of the solution was added.

Preparation of the Second Aqueous Solution B

[0089] Water, 7.5% by weight of sorbitol and 12.5% by weight of corn starch with respect to the total of the solution were mixed at ambient temperature; the solution was then brought to 70 C.

Application of the Second Coating

[0090] In a fluid-bed granulator, there were successively atomized on the granular material comprising sodium butyrate and the first coating and having an introduction temperature into the fluid bed of 35 C. the solutions A and B at 80 C. and 70 C., respectively. The air flow being introduced into the granulator had a temperature of 35 C. and a relative humidity of 1.0%.

[0091] This process lasted 2 hours at the end of which there is obtained a granular material comprising sodium butyrate, a first coating on this granular material and a second coating comprising sorbitol, corn starch, sodium alginate and guar gum on this first coating.

[0092] Subsequently, the temperature of the air being introduced into the granulator was brought to 55 C. until obtaining a residual relative humidity in the granular material of 1.0%, established on suitable samples of the material itself from the granulator. The composition of the granular material having this first coating and second coating obtained in this manner is set out in Table 2.

TABLE-US-00002 TABLE 2 Composition of the granular material having a first coating and a second coating Component % by weight Granular material with first coating 92.6 Second Sodium alginate 0.2 coating Guar gum 0.2 Sorbitol 2.6 Corn starch 4.4

Granulation

[0093] The granular material having a first coating and a second coating being discharged from the fluid-bed granulator was sieved over a suitable mesh so as to eliminate the granules having a diameter greater than 2 mm.

[0094] The granular material having this double coating and a diameter below 2 mm was again conveyed to the fluid-bed granulator and mixed together with isomalt, stevia and guar gum. The temperature of the air being introduced was brought to 65 C. and the mixing was continued until having a residual relative humidity in the granular material of 1.0%. Subsequently, the flavourings were added and mixing was continued for another 5 minutes.

[0095] The orally dispersible compound obtained in this manner was then discharged from the fluid-bed granulator and sieved over a suitable mesh so as to eliminate the granules having a diameter greater than 2 mm.

[0096] The composition of the orally dispersible compound obtained in this manner is set out in Table 3.

TABLE-US-00003 TABLE 3 Composition of the orally dispersible compound comprising a granular material having a first coating and a second coating Component % by weight Granular material having a first coating and a second 29.0 coating Isomalt 67.7 Stevia 0.2 Guar gum 2.0 Flavourings 1.1

Oral Dispersibility Tests

[0097] In order to evaluate the oral dispersibility of the composition to which the present invention relates, there was proposed a test in vivo according to the following description.

[0098] A quantity of orally dispersible compound of 1.5 grammes, which is indicated A in the table below and which has a composition according to what is set out in Table 3, was placed on the tongue of three different subjects who were asked to keep it still to the greatest possible extent. At predetermined intervals of time of 15 seconds, a visual examination of the compound itself was carried out, by asking the subjects to open their mouths.

[0099] The same type of test was carried out with the granular material which has a first coating and a second coating, which is indicated B and which has a composition according to what is set out in Table 2.

[0100] In this case, there were used both 1.5 g of the granular material B and 435 mg, that is to say, 29% of 1.5 g, equal to the quantity of the granular material B present in A used in the above test. The results obtained in the two cases were identical; therefore, the Table below sets out a single result for the granular material B.

[0101] Subject 1 is a male aged 31, subject 2 is a female aged 27 and subject 3 is a female aged 28.

[0102] Table 4 sets out the results of the observations, where A is intended to denote the orally dispersible compound and B is intended to denote the granular material having the first coating and the second coating.

TABLE-US-00004 TABLE 4 Results of the tests in vivo Subject 45 sec 2 min 3 min 1 A Became separated No longer any trace of A B The granules of B are still present 2 A Became partially No longer any separated trace of A B The granules of B are still present 3 A Became partially No longer any separated trace of A B The granules of B are still present

[0103] Though the subjects of the test differ in terms of sex and age, and similarly in terms of extent of the surface of the tongue, composition and flow of saliva, this test makes it clear that it was possible for all three subjects to take up the orally dispersible compound very easily and without using water within 3 minutes, while none of the three subjects was able to take up the granular material having the first coating and second coating without using water.