STORAGE STABLE MIXTURES

Abstract

The present invention relates to improved formulations of propandiol mononitrate and derivatives thereof as well as to the methods for production of such formulations.

Claims

1. A method of improving retention of a compound of formula (I): ##STR00002## wherein n is an integer from 1 to 15, R.sup.1 is selected from the group consisting of 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, and ONO.sub.2, and R.sup.8 is C.sub.1-C.sub.6alkyl, phenyl, with the proviso that when n is >3 the hydrocarbon chain may be interrupted by Oor NH in a powderous formulation comprising: (i) the compound according to formula (I), and (ii) silica, wherein the method comprises admixing the powderous formulation with a starch derived from potatoes, wheat, maize and/or cassava.

2. The method according to claim 1, wherein the retention of the compound of formula (I) after at least 4 weeks is at least 80%.

3. The method according to claim 1, wherein the retention of the compound of formula (I) after at least 4 weeks is at least 85%.

4. The method according to claim 1, wherein the retention of the compound of formula (I) after at least 4 weeks is at least 90%.

5. The method according to claim 1, wherein the retention of the compound of formula (I) after at least 4 weeks is at least 95%.

Description

EXAMPLES

General Information

A.) HPLC Method

[0123] Agilent High Performance Liquid Chromatography 1260 Infinity system, using an Aquasil C18, 1503 mm, 3 m column and detecting at 210 nm. The column oven was set to 23 C., the autosampler not temperature controlled. The mobile phase consisted of mobile phase A (940 mL Milli-Q-water+60 ml acetonitrile+1 mL methane sulfonic acid) and mobile phase B (800 ml Milli-Q-water+200 ml acetonitrile+1 mL methane sulfonic acid) which were used in gradient mode (0 min: 0% B, 15 min: 0% B, 15.5 min: 100% B, 21 min: 100% B, 21.5 min: 0% B, 25 min: 0% B (=end of run)) with a flow of 0.4 ml/min.

B.) Powderous Formulation Comprising Propandiol Mononitrate (PF-PDMN)

[0124] To 80 g of silica (Newsil C50) placed on a beaker, are added 80 g of a 20 wt.-% propandiol mononitrate (PDMN) solution in propyleneglycol under gentle agitation at room temperature. After 5 minutes agitation, the adsorption is completed and a free-flowing powder is obtained.

Example 1: Retention of PDMN in PF-PDMN Admixed With Different Carriers

[0125] 10 g of PF-PDMN and 90 g of an organic carrier as outlined in table 1 have been mixed with a TURBULA Shaker-Mixer (64 rotations/min) for 10 min, sieved through a 2 mm sieve and mixed again for 10 min to obtain homogenous mixtures (100 g batches). Then 10 g of the respective mixtures were stored in reclosed PE bags at 25 C. under controlled atmosphere (50% r.H) for 1 month. Afterwards the remaining content of PDMN was determined by HPLC. The results (as relative concentration to the initial value set to 100%) are presented Table 1.

TABLE-US-00001 TABLE 1 Retention of PDMN in PF-PDMN in dependence of various organic carriers # Organic carrier Retention [%] Inv 1 Maize starch 93 Ref 1 Rice Hulls 89 Ref 2 Modified starch* 48 *starch sodium octenyl succinate (OSA-starch).

[0126] As can be retrieved from table 1, the use of the starch according to the present invention resulted in an improved retention of the active compared to other organic carriers commonly used in the feed industry.

Example 2: Retention of PDMN in PF-PDMN Admixed With Different Carriers

[0127] 11 g of PF-PDMN and 11 g of the respective starch/starch derivative as outlined in table 2 have been mixed with a TURBULA Shaker-Mixer (64 rotations/min) for 10 min, sieved through a 2 mm sieve and mixed again for 10 min to obtain homogenous mixtures (22 g batches). Then two samples (5 g each) of the respective mixtures were stored in reclosed PE bags at 40 C. under controlled atmosphere (75% r.H) for 1 week. Afterwards the remaining content of PDMN was determined by HPLC. The results (as relative concentration to the initial value set to 100%) are presented Table 2.

TABLE-US-00002 TABLE 2 Retention of PDMN in PF-PDMN admixed with different starch types in a 1:1 ratio # Organic carrier Retention [%] Inv 2 Maize starch 92 Ref 3 Modified starch* 88 *starch sodium octenyl succinate (OSA-starch).

[0128] As can be retrieved from table 2, also at lower starch ratios the use of native starch resulted in an improved retention of the active compared to the use of modified (OSA) starch, even under stress conditions (i.e. high temperature and high humidity).