Solid composition for quick ingestion with facilitated swallowing, in the form of solid, non-agglomerated particles, comprising two different types of particles

Abstract

A solid composition with rapid ingestion and facilitated swallowing, in the form of non-agglomerated solid particles, said composition comprising the following two different types of particle: Pa particles, with very low solubility in saliva and comprising at least one active ingredient, and Ps particles, rapidly soluble in saliva, characterised by an apparent density equal to or greater than approximately 0.6 g.cm.sup.−3, advantageously equal to or greater than approximately 0.7 g.cm.sup.−3, and preferably between 0.7 and 1.5 g.cm.sup.−3 inclusive.

Claims

1. A solid composition for administration to a human or animal individual comprising: Pa particles comprising at least one active ingredient in sufficient quantity to administer a desired dose of active ingredient to said human or animal individual, wherein the Pa particles have very low solubility in saliva, and Ps particles comprising at least one polyol with low glycaemic index and at least one natural index and at least one natural organic acid or a salt thereof, the weight ratio of the at least one natural organic acid or salt thereof/the at least one polyol with low glycaemic index being between 0.01 and 1 inclusive, the Ps particles having an apparent density equal to or greater than approximately 0.6 g.cm.sup.−3 and being rapidly soluble in saliva; wherein said Ps particles are present in said composition in sufficient quantity to enable rapid ingestion and facilitated swallowing of said Pa particles in said human or animal individual; and wherein the composition is in the form of non-agglomerated solid particles.

2. The composition according to claim 1, comprising a homogeneous mixture of Pa and Ps particles.

3. The composition according claims 1, wherein said at least one natural organic acid, or a salt thereof, is present in the Ps particles in a mass percentage not exceeding 50% of the total mass of the Ps particles.

4. The composition according to claim 1, wherein the Ps particles have an average size less than or equal to approximately 500 μm.

5. The composition according to claim 1, wherein the Ps particles are free from disintegrating agents.

6. The composition according to claim 1, wherein the Pa particles are made up of or are coated with a hydrophobic material, wherein the Pa particles are protected from moisture, have limited solubility in saliva, or both; or wherein the release of at least one active ingredient contained therein in one or more parts of the digestive tract is modulated; or wherein the Pa particles are protected from moisture, have limited solubility in saliva, or both and wherein the release of at least one active ingredient contained therein in one or more parts of the digestive tract is modulated.

7. The composition according to claim 1, wherein the Pa particles have an average size of less than approximately 500 μm.

8. The composition according to claim 1, wherein the average size of the Ps particles and the average size of the Pa particles are no more than 50% different from each other.

9. The composition according to claim 1, wherein the composition is free from disintegrating agents.

10. The composition according to claim 1, wherein the ratio between the mass of Pa particles and the mass of Ps particles is less than 10.

11. The composition according to claim 10, wherein said ratio is less than or equal to 1.

12. A medicine or a food supplement for human or animal use, comprising the composition according to claim 1.

13. A sachet or stick comprising the composition according to claim 1.

14. Particles comprising at least one polyol with low glyaecmic index and at least natural organic acid or salt thereof, the weight ratio of the at least one natural organic acid or a salt thereof/the at least one polyol with low glycaemic index being between 0.01 and 1 inclusive, the particles having an apparent density equal to or greater than approximately 0.6 g.cm.sup.−3 and being rapidly soluble in saliva.

15. The composition of claim 1, wherein the polyol is erythritol, and wherein the erythritol has a mass percentage of at least 50% of the total mass of the Ps particles.

16. The composition of claim 1, wherein the Ps particles consist of at least one polyol with low glycaemic index.

17. The composition of claim 16, wherein the polyol is erythritol.

18. The composition of claim 10 wherein the ratio between the mass of Pa particles and the mass of Ps particles is less than or equal to 2.5.

Description

DETAILED DESCRIPTION

(1) The examples presented below make it possible to better illustrate the present invention. However, these examples must under no circumstances be regarded as limiting the scope of said invention in any way.

EXAMPLES

Example 1

Preparation of One Kilogram (1 kq) of Food Supplement Based on Zinqiber Officinale Composed of a Homogeneous Mixture of Pa and Ps Particles

(2) 10% by weight Pa particles and 90% by weight Ps particles are introduced into a rotary drum mixer, and are stirred for 15 minutes to form a homogenous mixture of white to white-cream coloured particles.

(3) Pa particles: The Pa particles are made up of a mixture of 40% extract of Zingiber officinale (ginger) root and 60% sorbitol monostearate, and prepared according to a beading technique (technique of nebulisation followed by cooling) well known to the person skilled in the art, in order to limit their solubility in the oral cavity. Therefore the Pa particles present very low solubility in saliva (inside the oral cavity): indeed, a quantity less than 5% of the mass of the active ingredient, gingerol, is dissolved after 10 seconds when the “reference test for determining particle solubility in saliva” defined above is applied, so as not to cause in particular an excessively spicy sensation in the patient's mouth. Granulometric analysis of the Pa particles according to the sieving method shows that more than 90% of them are less than 500 μm in size and less than 10% are less than 125 μm in size.

(4) Ps particles: The Ps particles are made up of a mixture of 99% erythritol and 1% citric acid, and are obtained by mixing in solution and then drying. The particles present an apparent density of between 0.7 and 0.8 g.cm.sup.−3 inclusive, and rapid solubilisation in saliva—in less than 20 seconds—when the “reference test for determining particle solubility in saliva” defined above is applied. Granulometric analysis of the Ps particles according to the sieving method shows that more than 90% of them are less than 710 pm in size and less than 10% are less than 125 μm in size. The homogeneity of the mixture thus formed is assessed by taking 3 samples of at least 1 g from the mixer in the vertical axis (top centre, middle centre, bottom centre) and assaying one of the active ingredients (gingerol) via a conventional liquid chromatography technique. The results obtained are set out in table 1 below and show a variation coefficient of less than 5%.

(5) TABLE-US-00001 TABLE 1 Sample Dosage (mg) Top 188 Middle 174 Bottom 178 Mean 180 Standard deviation 7.21 VC 4.01%

(6) This variation coefficient, of less than 5%, confirms that the mixture of Pa and Ps particles is homogeneous, as stated previously.

(7) The mixture thus obtained is particularly homogeneous and dense due to the high apparent density and/or the specific granulometry of the Ps particles (of between 0.1 and 1 millimetre). Furthermore, since the average particle size is more than 50 μm, it facilitates the preparation operations by limiting particle dissemination during the manufacturing operations, as well as the risk of inhalation of the product by the user when opening and taking the product.

(8) In addition, said mixture possesses sufficient pourability (measured via the European Pharmacopoeia's so-called “funnel” test (see European Pharmacopoeia 8.0, “2. Analytical methods”, 2.9.16) which enables it to be packed and taken directly into the user's mouth (oral administration) without requiring exogenous water intake or a prior step of dilution in a glass of water.

(9) The homogeneous mixture of Pa and Ps particles proves particularly stable in particular because of its preparation method, which makes it possible to separately prepare the Pa particles, on the one hand, and Ps particles on the other.

Example 2

Preparation of One Kilogram (1 kg) of Food Supplement Based on Vaccinum Macrocarpon Composed of a Homogeneous Mixture of Pa and Ps Particles

(10) 40% by weight Pa particles and 60% by weight Ps particles are introduced into a rotary drum mixer, and are stirred for 15 minutes to form a homogenous mixture of particles.

(11) Pa particles: The Pa particles are made up of a mixture of 40% extract of Vaccinium macrocarpon (cranberry) and 60% glycerol monostearate, and prepared according to a beading technique (technique of nebulisation followed by cooling) well known to the person skilled in the art, in order to limit their solubility in the oral cavity. Therefore the Pa particles present very low solubility in saliva (inside the oral cavity): indeed, a quantity less than 5% of the mass of the active ingredient (proanthocyanidins or PACs) is dissolved after 10 seconds when the “reference test for determining particle solubility in saliva” defined above is applied, so as not to cause in particular excessive acidity in the patient's mouth. Granulometric analysis of the Pa particles according to the sieving method shows that more than 90% of them are less than 500 μm in size and less than 10% are less than 125 μm in size.

(12) Ps particles: The Ps particles are made up of a mixture of 98.5% erythritol and 1.5% citric acid, and are obtained by granulation and then drying. The particles present an apparent density of around 0.8 g.cm.sup.−3, and rapid solubilisation in saliva—in less than 20 seconds—when the “reference test for determining particle solubility in saliva” defined above is applied. Granulometric analysis of the Ps particles according to the sieving method shows that more than 90% of them are less than 710 μm in size and less than 10% are less than 125 μm in size.

Example 3

Preparation of One Kilogram (1 kq) of Food Supplement Based on Tagetes Erecta Composed of a Homogeneous Mixture of Pa and Ps Particles

(13) 20% by weight Pa particles and 80% by weight Ps particles are introduced into a rotary drum mixer, and are stirred for 15 minutes to form a homogenous mixture of particles.

(14) Pa particles: The Pa particles are made up of a mixture of 40% Tagetes erecta extract (lutein), 40% microcrystalline cellulose and 20% hypromellose (hydroxypropyl methylcellulose), and prepared according to a granulation technique followed by film-coating on a fluid air bed well known to the person skilled in the art, in order to improve their stability. The Pa particles also present low solubility in saliva (in the oral cavity) according to the “reference test for determining particle solubility in saliva” defined above, so as not to cause an excessively pronounced taste in the patient's mouth. Granulometric analysis of the Pa particles according to the sieving method shows that more than 90% of them are less than 500 μm in size and less than 10% in size are less than 125 μm.

(15) Ps particles: The Ps particles are made up of a mixture composed of 60% sorbitol, 20% erythritol, 18% tricalcium citrate and 2% citric acid, and are obtained by granulation and drying. The particles present an apparent density of around 0.8 g.cm.sup.−3, and rapid solubilisation in saliva—in less than 20 seconds—when the “reference test for determining particle solubility in saliva” defined above is applied. Granulometric analysis of the Ps particles according to the sieving method shows that more than 90% of them are less than 710 μm in size and less than 10% are less than 125 μm in size.

Example 4

Preparation of One Kilogram (1 kg) of Food Supplement Based on Chlorella and Carbo Vegetalis Composed of a Homogeneous Mixture of Pa and Ps Particles

(16) 70% by weight of a mixture of Pa particles and 30% by weight Ps particles are introduced into a rotary drum mixer, and are stirred for 15 minutes to form a homogenous mixture of particles.

(17) Mixture of Pa particles: this mixture comprises equal parts of: Pa1 particles, made up of 40% Chlorella and 60% sorbitol monostearate, and Pa2 particles, made up of 40% Carbo vegetalis (vegetable carbon) and 60% sorbitol monostearate; said Pa1 and Pa2 particles being prepared according to a beading technique (nebulisation followed by cooling) well known to the person skilled in the art, in order to limit dissemination in the oral cavity of the active ingredients. Therefore the Pa particles present very low solubility in saliva (inside the oral cavity) according to the “reference test for determining particle solubility in saliva” defined above, so as not to cause, in particular, dissemination and coloration of the mucous membranes and the patient's mouth. Granulometric analysis of the Pa particles according to the sieving method shows that more than 90% of them are less than 500 μm and less than 10% are less than 125 μm.

(18) Ps particles: The Ps particles are made up of a mixture of 70% erythritol and 28% xylitol, and 2% citric acid, and are obtained by mixing in solution and then drying. The particles present an apparent density of around 0.8 g.cm.sup.−3, and rapid solubilisation in saliva—in less than 20 seconds—when the “reference test for determining particle solubility in saliva” defined above is applied. Granulometric analysis of the Ps particles according to the sieving method shows that more than 90% of them are less than 710 μm in size and less than 10% are less than 125 μm.

Example 5

Preparation of One Kilogram (1 kg) of Pharmaceutical Preparation Based on Ibuprofen Composed of a Homogeneous Mixture of Pa and Ps Particles

(19) 50% by weight Pa particles and 50% by weight Ps particles are introduced into a rotary drum mixer, and are stirred for 15 minutes to form a homogenous mixture of particles.

(20) Pa particles: The Pa particles are made up of a mixture of 80% ibuprofen and 20% sorbitol monostearate, and prepared according to a hot melt coating technique well known to the person skilled in the art, in order to prevent direct contact between the ibuprofen and the patient's oral mucosa. Therefore the Pa particles present very low solubility in saliva (inside the oral cavity): indeed a quantity of less than 5% of the mass of active ingredient ibuprofen is dissolved after 10 seconds when the “reference test for determining particle solubility in saliva” defined above is applied, so as to prevent local irritation as well as a risk of absorption via the oral mucosa. Granulometric analysis of the Pa particles according to the sieving method shows that more than 90% of them are less than 500 μm in size and less than 10% are less than 125 μm in size.

(21) Ps particles: The Ps particles are made up of a mixture composed of 90% erythritol, 9% tricalcium citrate and 1% citric acid, and are obtained by granulation. The particles present an apparent density of around 0.8 g.cm.sup.−3, and rapid solubilisation in saliva in accordance with the “reference test for determining particle solubility in saliva” defined above. Granulometric analysis of the Ps particles according to the sieving method shows that more than 90% of them are less than 710 μm in size and less than 10% are less than 125 μm.

Example 6

Preparation of One Kilogram (1 kg) of Pharmaceutical Preparation Based on 5 ASA (5 Aminosalicylic Acid) Composed of a Homogeneous Mixture of Pa and Ps Particles

(22) 70% by weight Pa particles and 30% by weight Ps particles are introduced into a rotary drum mixer, and are stirred for 15 minutes to form a homogenous mixture of particles.

(23) Pa particles: The Pa particles are made up of a mixture of 80% 5-ASA and 20% a pharmaceutical grade methacylic polymer insoluble in acid medium, and prepared according to a technique of film coating technique on a fluid air bed (FAB) well known to the person skilled in the art, in order to prevent direct contact between the 5 ASA and the patient's oral mucosa. Therefore the Pa particles present a very low solubility in saliva (inside the oral cavity) according to the “reference test for determining particle solubility in saliva” defined above, and enable a gradual release of the active substance (5ASA) into the digestive tube (colon) in order to obtain optimum efficacy. Granulometric analysis of the Pa particles according to the sieving method shows that more than 90% of them are less than 500 μm in size and less than 10% are less than 125 μm in size.

(24) Ps particles: The Ps particles are made up of a mixture composed of 90% erythritol, 9% tricalcium citrate and 1% citric acid, and are obtained by granulation. The particles present an apparent density of around 0.8 g.cm.sup.−3, and rapid solubilisation in saliva according to the “reference test for determining particle solubility in saliva” defined above. Granulometric analysis of the Ps particles according to the sieving method shows that more than 90% of them are less than 710 μm in size and less than 10% are less than 125 μm.

Example 7

Preparation of One Kilogram (1 kq) of Food Supplement Based on Curcuma Longa Composed of a Homogeneous Mixture of Pa and Ps Particles

(25) 50% by weight Pa particles and 50% by weight Ps particles are introduced into a rotary drum mixer, and are stirred for 15 minutes to form a homogenous mixture of particles.

(26) Pa particles: The Pa particles are made up of a mixture of 75% Curcuma Longa extract and 25% sorbitol monostearate, and prepared according to a hot melt coating technique well known to the person skilled in the art, in order to prevent direct contact between the plant extract and the patient's oral mucosa. Therefore the Pa particles present very low solubility in saliva (inside the oral cavity): indeed a quantity less than 5% of the mass of the active ingredient (curcumin) is dissolved after 10 seconds when the “reference test for determining particle solubility in saliva” defined above is applied, so as to prevent in particular coloration of the oral mucosa. Granulometric analysis of the Pa particles according to the sieving method shows that more than 90% of them are less than 710 pm in size and less than 10% are less than 125 μm in size.

(27) Ps particles: The Ps particles are made up of a mixture composed of 99% erythritol and 1% citric acid, and are obtained by granulation. The particles present an apparent density of around 0.8 g.cm.sup.−3, and rapid solubilisation in saliva—in less than 20 seconds—when the “reference test for determining particle solubility in saliva” defined above is applied. Granulometric analysis of the Ps particles according to the sieving method shows that more than 90% of them are less than 710 μm in size and less than 10% are less than 125 μm in size.

Example 8

Preparation of One Kilogram (1 kg) of Food Supplement Based on Boswellia Serrata Composed of a Homogeneous Mixture of Pa and Ps Particles

(28) 40% by weight Pa particles and 60% by weight Ps particles are introduced into a rotary drum mixer, and are stirred for 15 minutes to form a homogenous mixture of particles.

(29) Pa particles: The Pa particles are made up of a mixture of 75% Boswellia serrata extract and 25% sorbitol monostearate, and prepared according to a hot melt coating technique well known to the person skilled in the art, in order to prevent direct contact between the plant extract and the patient's oral mucosa. Therefore the Pa particles present very low solubility in saliva (inside the oral cavity): indeed a quantity less than 10% of the mass of the active ingredient (Boswellic acid) is dissolved after 10 seconds when the “reference test for determining particle solubility in saliva” defined above is applied, so as to prevent an unpleasant sensation. Granulometric analysis of the Pa particles according to the sieving method shows that more than 90% of them are less than 710 μm in size and less than 10% are less than 125 μm in size.

(30) Ps particles: The Ps particles are made up of a mixture composed of 99% erythritol and 1% citric acid, and are obtained by granulation. The particles present an apparent density of around 0.8 g.cm.sup.−3, and rapid solubilisation in saliva—in less than 20 seconds—when the “reference test for determining particle solubility in saliva” defined above is applied. Granulometric analysis of the Ps particles according to the sieving method shows that more than 90% of them are less than 710 μm in size and less than 10% are less than 125 μm in size.

Example 9

Preparation of One Kilogram (1 kg) of Food Supplement Based on Whitania Somnifera Composed of a Homogeneous Mixture of Pa and Ps Particles

(31) 40% by weight Pa particles and 60% by weight Ps particles are introduced into a rotary drum mixer, and are stirred for 15 minutes to form a homogenous mixture of particles.

(32) Pa particles: The Pa particles are made up of a mixture of 75% Whitania somnifera extract and 25% sorbitol monostearate, and prepared according to a hot melt coating technique well known to the person skilled in the art, in order to prevent direct contact between the plant extract and the patient's oral mucosa. Therefore the Pa particles present very low solubility in saliva (inside the oral cavity): indeed a quantity less than 5% of the mass of the active ingredient (glycowithanolide) is dissolved after 10 seconds when the “reference test for determining particle solubility in saliva” defined above is applied. Granulometric analysis of the Pa particles according to the sieving method shows that more than 90% of them are less than 710 μm in size and less than 10% are less than 125 μm in size.

(33) Ps particles: The Ps particles are made up of a mixture composed of 99% erythritol and 1% citric acid, and are obtained by granulation. The particles present an apparent density of around 0.8 g.cm.sup.−3, and rapid solubilisation in saliva—in less than 20 seconds—when the “reference test for determining particle solubility in saliva” defined above is applied. Granulometric analysis of the Ps particles according to the sieving method shows that more than 90% of them are less than 710 μm in size and less than 10% are less than 125 μm in size.

Example 10

Preparation of One Kilogram (1 kq) of Pharmaceutical Preparation Based on Paracetamol Composed of a Homogeneous Mixture of Pa and Ps Particles

(34) 62.5% by weight Pa particles and 37.5% by weight Ps particles are introduced into a rotary drum mixer, and are stirred for 15 minutes to form a homogenous mixture of particles.

(35) Pa particles: The Pa particles are made up of a mixture of 80% paracetamol and 20% sorbitol monostearate, and prepared according to a hot melt coating technique well known to the person skilled in the art, in order to prevent direct contact between the paracetamol and the patient's oral mucosa. Therefore the Pa particles present very low solubility in saliva (inside the oral cavity): indeed a quantity of less than 5% of the mass of active ingredient paracetamol is dissolved after 10 seconds when the “reference test for determining particle solubility in saliva” defined above is applied, so as to prevent a risk of absorption via the oral mucosa. Granulometric analysis of the Pa particles according to the sieving method shows that more than 90% of them are less than 500 μm in size and less than 10% are less than 125 μm in size.

(36) Ps particles: The Ps particles are made up of a mixture composed of 90% erythritol, 9% tricalcium citrate and 1% citric acid, and are obtained by granulation. The particles present an apparent density of around 0.8 g.cm.sup.−3, and rapid solubilisation in saliva according to the “reference test for determining particle solubility in saliva” defined above. Granulometric analysis of the Ps particles according to the sieving method shows that more than 90% of them are less than 710 μm in size and less than 10% are less than 125 μm in size.

Example 11

Evaluation of the Properties of the Composition According to the Invention in Terms of Rapidity of Ingestion and Ease of Swallowing

(37) A study encompassing 10 subjects aged between 12 and 77 years inclusive (of which 5 women and 5 men) was conducted in order to evaluate the properties of the invention in terms of rapidity of ingestion and ease of swallowing.

(38) The rapidity of ingestion criterion was evaluated as follows: A: Less than 10 seconds B: Between 10 seconds and 20 seconds C: Between 20 seconds and 30 seconds D: More than 30 seconds

(39) The ease of swallowing criterion was evaluated as follows: 1: No difficulty in swallowing 2: Slight discomfort in swallowing 3: Medium discomfort in swallowing 4: Severe discomfort in swallowing The composition described in example 1 was evaluated and table 2 below brings together the results obtained.

(40) TABLE-US-00002 TABLE 2 Ingestion Ease of Subject Age Sex time swallowing 1 24 F A (5 s) 1 2 47 M A (4 s) 1 3 35 F A (7 s) 1 4 15 M A (4 s) 1 5 68 F B (9 s) 1 6 12 F A (8 s) 1 7 77 M A (8 s) 1 8 64 M A (5 s) 1 9 33 F A (4 s) 1 10 29 M A (4 s) 1 Results Obtained: Ingestion time: all the subjects were able to ingest the composition according to example 1 in less than 10 seconds (of which 5 subjects in less than 5 seconds).

(41) Ease of swallowing: all the subjects swallowed the composition very easily and did not observe any discomfort upon swallowing.

(42) The composition according to the invention makes it possible to obtain a galenic form or packaging in the form of a mixture of particles in sachet or stick form. Therefore the invention also relates to a dose of active ingredient in the form of the mixture described above, preferably bagged hermetically in an oblong or rectangular container, part of which can be easily torn off. Such presentations are also an object of the invention.

(43) Advantageously, the total mass of the composition according to the invention that can be used for administering a dose of active ingredient(s) to a human being may range from 0.1 mg to 10 g, advantageously from 0.5 g to 5 g, and preferably from 1 g to 3 g.

(44) The invention also relates to use of Ps particles such as described above for the manufacture of a composition in the form of a mixture of particles, in particular that described in the present application.

(45) The invention also relates to the use of Pa particles such as described above for the manufacture of a composition in the form of a mixture of particles, in particular that described in the present application.

(46) The invention also relates to a method of administering a dose of active ingredient(s) to a human or animal individual by ingestion of a mixture of particles as described in the present application. In particular, this method comprises placing the mixture of solid particles directly on the tongue. Advantageously, no additional/exogenous liquid ingestion (for example in the form of a glass of water) is required.

(47) The invention also relates to a manufacturing method of the mixture described above.

(48) This method comprises a step of mixing the Pa and Ps particles to obtain a homogeneous mixture of non-agglomerated solid particles. According to a preferred aspect, the Ps and Pa particles are manufactured prior to the mixing step.