COMPRESSED TABLETS

Abstract

The present invention relates to compressed tablets comprising 3-nitrooxypropanol or derivatives thereof and a gluten as well as to the production of such tablets.

Claims

1. A compressed tablet comprising (i) At least 0.01 wt-%, based on the total weight of the compressed tablet, of a compound of formula (I) ##STR00002## wherein n is an integer from 1 to 46 R.sup.1 is H, C.sub.1-C.sub.6alkyl, phenyl, OH, NH.sub.2, CN, COOH, O(CO)R.sup.8, NHC(O)R.sup.8, SO.sub.2NHR.sup.8, or ONO.sub.2, and R.sup.8 is C.sub.1-C.sub.6alkyl, phenyl, pyridyl such as preferably 2-pyridyl with the proviso that when n is >3 the hydrocarbon chain may be interrupted by O or NH, and (ii) at least 30 wt.-%, based on the total weight of the compressed tablet, of gluten.

2. The compressed tablet according to claim 1, wherein the compound of formula (I) is absorbed on a carrier.

3. The compressed tablet according to claim 1 or 2, claim 1, comprising at least 40 wt.-%, more preferably at least 50%, even more preferably at least 60 wt.-% and most preferably at least 70 wt.-%, based on the total weight of the compressed tablet, of gluten.

4. The compressed tablet according to claim 1, comprising 0.01 to 10 wt.-%, preferably of 0.05 to 5 wt.-%, most preferably 0.075 to 2.5 wt.-%, based on the total weight of the tablet of a compound of formula (I).

5. The compressed tablet according to claim 1, wherein the gluten is wheat gluten, preferably vital wheat gluten.

6. The compressed tablet according to claim 1, wherein n is an integer between 3 and 9 and R.sup.1 is OH, COOH or ONO.sub.2.

7. The compressed tablet according to claim 1, wherein the compound of formula (I) is selected from the group consisting of 3-nitrooxypropanol, 9-nitrooxynonanol, 5-nitroxy pentanoic acid, 6-nitroxy hexanoic acid, Bis(2-hydroxyethyl)amine dinitrate, 1,4-bis-nitrooxybutane and 1,5-bis-nitrooxypentane, preferably 3-nitrooxypropanol.

8. The compressed tablet according to claim 1 further comprising at least one additive in an amount selected in the range of 1 to 40 wt.-%, preferably in the range of 1 to 30 wt.-%, more preferably in the range of 1 to 20 wt.-% based on the total weight of the tablet.

9. A compressed tablet according to claim 1 wherein the additive is selected from the group consisting of fillers, lubricants, proteins, dyes, flavours, sweeteners, minerals, vitamins, and antioxidants.

10. A compressed tablet according to claim 1 consisting essentially. (i) 0.01 to 10 wt-%, preferably 0.05 to 5 wt.-%, more preferably 0.075 to 2.5 wt.-% based on the total weight of the compressed tablet, of a compound of formula (I), and (ii) at least 50 wt.-%, preferably at least 60 wt.-%, more preferably at least 70 wt.-% based on the total weight of the formulation, of gluten, and (iii) 1 to 40 wt-%, preferably 1 to 30 wt.-%, more preferably 1 to 20 wt.-% based on the total weight of the compressed tablet, of at least one additive, and (iv) 0 to 12 wt-%, preferably 0 to 10 wt.-%, more preferably 0 to 8 wt.-%, most preferably 0 to 6 wt.-% based on the total weight of the compressed tablet, of water.

11. The compressed tablet according to claim 1, wherein the compound of formula (I) is incorporated into the tablets as a powderous formulation consisting essentially of a compound of formula (I), an edible oil and a carrier.

12. The compressed tablet according to claim 11, wherein the powderous formulation consists essentially of 5-20 wt.-% of a compound of formula (I), 20 to 50 wt.-% of propyleneglycol and 30 to 60 wt.-% of silica.

13. The compressed tablet according to claim 1, wherein the tablet contains an additional coating.

14. The compressed tablet according to claim 13, wherein the coating is selected from the group consisting of glycerine monostearate, carnauba wax, candelilla wax, sugarcane wax, palmitic acid, stearic acid hydrogenated cottonseed oil, hydrogenated palm oil and hydrogenated rapeseed oil as well as mixtures thereof.

15. A process for the preparation of a compressed tablet according to claim 1, which process comprises admixing the ingredients and compressing the ingredients at a pressure of at least 5 KN.

Description

EXAMPLES

[0082] 1a: Preparation of a Powderous Formulation (Form (I))

[0083] 50 g of 20 wt.-% 3-nitrooxypropanol solution in propyleneglycol was added under gentle agitation to 50 g silica which was placed on a beaker at RT (20 C.). After 5 minutes agitation, the adsorption is completed and a free-flowing powder is obtained. The powderous formulations are then allowed to stay at RT for another hour before use.

[0084] 1b: Preparation of Tablets:

[0085] 300 g powder mixture including Form (I) was prepared as outlined in table 2 by incorporating the listed ingredients step by step in a 1 L plastic container. The powder mix was mixed using a Bachofen Turbula mixer T2C for 10 min at 63 rpm then sieved through a 1.25 mm sieve then mixed again during 10 min at 63 rpm, then sieved again through a 1.25 mm sieve and finally mixed for another 10 min at 63 rpm. Following mixing as outlined above, the loose powder mixture was compressed using a tablet press Korsch XP1 to produce 1 g tablets using a compression force of 98 kN.

[0086] 1c: Tablet Dispersion Properties

[0087] To test tablet disintegration properties one tablet as outlined in table 2 was added into 100 mL tap water. A visual observation was made initially and 24 hours. The results thereof are outlined in table 1 and FIGS. 1 to 4.

TABLE-US-00001 Visual appearance Tablet initial after 24 h Rating Figure R2 intact cracked Not OK 1 R3 intact cracked Not OK 2 R4 intact cracked Not OK 3 I1 intact intact OK 4

[0088] 1d: Release Study:

[0089] The respective tablets were then placed in a beaker with 100 ml of demineralised water at room temperature. Each experiment was done in duplicate. After 5, 15, 30, 60, 90 minutes and 2, 6 and 24 hours 1 mL solution is taken out of the beaker and analysed for its 3-nitrooxypropanol content (HPLC). Time of 50% release is given in Table 2 (calculated by mathematical extrapolation of the obtained data points).

TABLE-US-00002 TABLE 2 # Ingredient R1 R2 R3 R4 I1 I2 I3 I4 I5 I6 I7 I8 1 Form (I) 10 10 10 10 10 10 10 10 10 10 10 10 2 Microcrystalline 89 25 10 20 30 cellulose 3 Magnesium- 1 stearate 4 Calcium- 1 1 1 1 1 1 1 1 1 stearate 5 Monocalcium- 21 21 phosphate 6 Limestone 50 25 10 20 30 49 7 Gluten 18 18 89 79 69 59 79 69 59 40 Release after [h] 0 0.2 0.5 0.75 7 6.5 4 2 6.5 4 2 2 1) Form prepared as outlined in example 1 2) Avicel PH102/FMC Biopolymer 3) Parteck LUB Mg-stearate/Merck 4) Calcium stearate/Riebel-de Han 5) Monocalciumphosphate/Sigma-Aldrich 6) Avicarb/OMYA 7) Vitene/Roquette (Vital wheat Gluten)

[0090] As can be retrieved from table 2, the tablets according to the present invention show a significantly increased retention of the active.