PIROCTONE OLAMINE RECRYSTALLIZATION

Abstract

The present invention relates to a process for recrystallizing piroctone olamine, to a process for preparing piroctone olamine crystals and to piroctone olamine crystals which may be obtained by such processes.

Claims

1. A process for the recrystallisation of piroctone olamine, comprising: a) Dissolving piroctone olamine in a solvent comprising at least one alcohol, wherein dissolving takes place at a dissolution temperature, which is a temperature above 50 degrees Celsius and below the boiling point of the alcohol; b) Cooling the solution from the dissolution temperature to a temperature between 1 and 15 degrees Celsius for a period up to 10 hours; and c) Recovering crystals of piroctone olamine.

2. The process of claim 1, wherein in a) 1.5 to 4 kg, of solvent are used per kilogram of piroctone olamine.

3. The process of claim 1, furthering comprising the step of adding crystals of piroctone olamine for seeding.

4. The process of claim 1, wherein the cooling takes place in two steps: i. In a first cooling step, cooling the solution from the dissolution temperature to a temperature between 20 and 40 degrees Celsius for a first cooling period which lasts up to 5 hours; ii. In a second cooling step, cooling the solution from a temperature between 20 and 40 degrees Celsius to a temperature between 1 and 15 degrees Celsius for a second cooling period which lasts up to 5 hours.

5. The process of claim 1, wherein the at least one alcohol is selected from the group consisting of methanol, ethanol, propanol, isopropanol, n-butanol, isobutanol and mixtures thereof.

6. The process of claim 1, wherein the at least one alcohol comprises isopropanol.

7. The process of claim 1, wherein the solvent consists of isopropanol.

8. The process of claim 1, wherein the dissolution temperature is from 60 to 82.5 degrees Celsius.

9. A process for the preparation of piroctone olamine crystals, comprising: a) Dispersing piroctone olamine in a solvent comprising at least one alcohol, wherein dispersing takes place at a dispersion temperature, which is a temperature above 50 degrees Celsius and below the boiling point of the alcohol; b) Cooling the dispersion from the dispersion temperature to a temperature between 1 and 15 degrees Celsius for a period up to 15 hours, preferably from 10 minutes to 15 hours, more preferably from 1 to 12 hours; c) Recovering crystals of piroctone olamine.

10. The process of claim 9, wherein in a) 1 to 3 kg, of solvent are used per kilogram of piroctone olamine.

11. The process of claim 9, wherein the cooling takes place in two steps: In a first cooling step, cooling the dispersion from the dispersion temperature to a temperature between 20 and 40 degrees Celsius for a first cooling period which lasts up to 10 hours; In a second cooling step, cooling the dispersion from a temperature between 20 and 40 degrees Celsius to a temperature between 1 and 15 degrees Celsius for a second cooling period which lasts up to 5 hours.

12. The process of claim 9, wherein the at least one alcohol is selected from the group consisting of methanol, ethanol, propanol, isopropanol, n-butanol, isobutanol and mixtures thereof.

13. The process of claim 9, wherein the at least one alcohol comprises isopropanol.

14. The process of claim 9, wherein the solvent consists isopropanol.

15. The process of claim 9, wherein the dispersion temperature is from 60 to 82.5 degrees Celsius.

16. A piroctone olamine crystal having an average width to length ratio of greater than 1:4.

17. The piroctone olamine crystal of claim 16, having d.sub.50 of greater than 110 micrometres.

18. The piroctone olamine crystal of claim 16 having d.sub.10 greater than 30 micrometres.

19. A piroctone olamine crystal having an average width to length ratio of greater than 1:4 obtainable by a process as defined in claim 1.

20. A piroctone olamine crystal, obtainable by a process as defined in claim 9.

Description

[0049] The invention will now be further described with reference to the accompanying drawings, in which:

[0050] FIG. 1 illustrates a microscope image of some recrystallized piroctone olamine crystals, The image is divided into 4 parts using a reticle scale in preparation for making width and length measurements in the fashion described below.

[0051] FIG. 2 illustrates the volumetric distribution density of particles, q (left hand y-axis) and the volumetric cumulative distribution Q(r) (right hand y-axis) versus diameter (x-axis) of particles of piroctone olamine which have not been recrystallized according to the invention.

[0052] FIG. 3 illustrates the volumetric distribution density of particles, q (left hand y-axis) and the volumetric cumulative distribution Q(r) (right hand y-axis) versus diameter (x-axis) of particles of piroctone olamine according to Example 3, which have been subject to a recrystallization according to the invention.

[0053] FIG. 4 illustrates a comparison of time consolidations of piroctone olamine, which has been recrystallized using the method of the invention (left hand graph) and non-recrystallized piroctone olamine (right hand graph).

PARTICLE SIZE DISTRIBUTION MEASUREMENT METHOD

[0054] A Horiba LA-950 particle size analyzer was used for measuring the diamter, the volumetric distribution density and the volumetric cumulative distribuition of the product. The analyzer uses a laser diffraction method (ISO 13320:2009, Fraunhofer Diffraction Method) to measure the distribution and is based on the direct proportionality of the intensity of light scattered by a particle, to the diameter. Furthermore the scattering angle is inversely proportional to the diameter and vice versa.

[0055] In preparation for the analysis, the required amount of product is placed on a sieve with a mesh size of 1 mm. The product is sieved with an amplitude of 1.5 mm for 3 minutes.

[0056] The required amount of sieved product is added to the gutter of the dry dispersion unit.

[0057] Three measurements were made in the HORIBA LA-950 particle size analyzer with the following parameters: [0058] Gutter starting value 85-110 (unit-less), automatic control [0059] Dispersing pressure 0.3 MPa

[0060] The three measurements are combined with the software to form an averaged measurement. For analysis the focus is on d.sub.10 and d.sub.50 volume fractions.

[0061] Measurement the Width/Length Ratio of the Piroctone Olamine Crystals

[0062] A small amount of sieved product (see above) is spread on a Petri dish with a spatula.

[0063] Under a microscope, a position is sought in which isolated particles are clearly visible. The microscope used was a Keyence VHX 2000 series digital micoscope with a VH-Z20W zoom lens, using a VHX-S90BE free angle observation system. The microscope does not form part of the invention and a skilled person could select suitable alternative microscopes.

[0064] The limits are set for the depth of field and an image in the appropriate magnification with the depth of field function of the microscope made.

[0065] Pictures are taken at the following magnifications ×50, ×100, 150, ×200 in order to obtain an overall impression of the bulk crystals.

[0066] A position on the Petri dish is needed in which an area of 3×3 images can be made with as many individual particles as possible.

[0067] A 3×3 image is taken at a magnification of ×200.

[0068] The image is divided into 4 parts using a reticle scale. In each quarter 5 representative particles are selected (20 particles in total). For each of these 20 particles, the width (w) and length (L) and the w/L ratio are determined. The average w/L ratio for all the particles is then calculated, which is the sum of the measured w/L divided by the number of particles (Σw/L)/20).

[0069] Flowability Measurement

[0070] Clumping of the crystals may be regarded as a low degree of flowability. In order to obtain an objective measurement of clumping, therefore, the crystals' flowability may be measured. The skilled person would be aware of other ways to characterize clumping.

[0071] The flowability of a bulk solid may be characterized by its unconfined yield strength, σ.sub.c, in dependence on consolidation stress, σ.sub.1, and storage period, t. Usually the ratio ff.sub.c of consolidation stress, al, to unconfined yield strength, σ.sub.c, is used to characterize flowability numerically:

ff.sub.c=σ.sub.1/σ.sub.c

[0072] The larger ff.sub.c is, i.e., the smaller the ratio of the unconfined yield strength, σ.sub.c, to the consolidation stress, al, the better a bulk solid flows. Flow behavior is defined as follows:

[0073] ff.sub.c of less than 1, not flowing

[0074] ff.sub.c from 1 to less than 2, very cohesive

[0075] ff.sub.c from 2 to less than 4, cohesive

[0076] ff.sub.c from 4 to less than 10, easy flowing

[0077] ff.sub.c of greater than 10, free flowing

[0078] The parameter ff.sub.c may be generated using a ring sheer test in the fashion described by Schulze, D (2009) “Pulver and Schüttgüter”, 2.sup.nd Edition, Springer, Berlin. This method does not form part of the present invention and is merely referred to as one way to characterize flowability in order to demonstrate the effect of the more flowable nature of the recrystallized crystals according to the invention. The skilled person is aware of other ways to characterize flowability.

LABORATORY SYNTHESIS EXAMPLES

Example 1

[0079] Raw Materials:

TABLE-US-00001 Raw material Quantity Equivalents Piroctone Olamine 100 kg 1.0 Ethanol 200 kg 2.74 Two batches of 37 L

[0080] Procedure: [0081] 1. Clean and dry the reactor. [0082] 2. Charge ethanol (200 kg) at 25-30 degrees Celsius. [0083] 3. Charge piroctone olamine (100 Kg) at 25-30 degrees Celsius. [0084] 4. Heat the mass to 70 degrees Celsius. [0085] 5. Maintain at 70-75 degrees Celsius for 30 minutes. [0086] 6. Check for dissolution (clear solution should be observed). [0087] 7. If incomplete dissolution, maintain at 70-75 degrees Celsius for another 30 minutes and check for clarity. [0088] 8. Gradually cool the mass to 25-30 degrees Celsius over a period of 3-4 hrs. [0089] 9. Cool the mass to 8-10 degrees Celsius over a period of 2 hours. [0090] 10. Maintain at 8-10 degrees Celsius for 1 hour. [0091] 11. Centrifuge at 8-10 degrees Celsius, wash centrifuge with chilled (at 5-10 degrees Celsius) ethanol (wash twice with 37 L). [0092] 12. Spin dry for 30 min. [0093] 13. Unload the wet in to poly bags and weigh the material. [0094] 14. Dry the material in hot air oven below 45 degrees Celsius for 4 hours. [0095] 15. Dry the material at 60 degrees Celsius until 0.3% wt liquid. [0096] 16. 79.1 kg of wet product/77.4 kg dry product was obtained.

Example 2

[0097] Raw Materials:

TABLE-US-00002 Raw material Quantity Equivalents Piroctone Olamine 100 kg 1.0 Isopropyl alcohol 200 kg 2.74 Two batches of 37 L

[0098] Procedure: [0099] 1. Clean and dry the reactor. [0100] 2. Charge Isopropyl alcohol (200 kg) at 25-30 degrees Celsius. [0101] 3. Charge piroctone olamine (100 Kg) at 25-30 degrees Celsius. [0102] 4. Heat the mass to 70 degrees Celsius. [0103] 5. Maintain at 70-75 degrees Celsius for 30 minutes. [0104] 6. Check for dissolution (clear solution should be observed). [0105] 7. If incomplete dissolution, maintain at 70-75 degrees Celsius for another 30 minutes and check for clarity. [0106] 8. Gradually cool the mass to 8-10° C. over a period of 4-5 hrs. [0107] 9. Maintain at 8-10 degrees Celsius for 1 hour. [0108] 10. Centrifuge at 8-10 degrees Celsius, wash centrifuge with chilled (at 5-10 degrees Celsius) isopropyl alcohol (wash twice with 37 L). [0109] 11. Spin dry for 30 min. [0110] 12. Unload the wet in to poly bags and weigh the material. [0111] 13. Dry the material in hot air oven below 45 degrees Celsius for 4 hours. [0112] 14. Dry the material at 60 degrees Celsius until 0.3% wt liquid. [0113] 15. 92.5 kg of wet product/90.5 kg dry product was obtained.

Example 3

[0114] Raw Materials:

TABLE-US-00003 Raw material Quantity Equivalents Piroctone Olamine 100 kg 1.0 Isopropyl alcohol 200 kg 2.74 Two batches of 37 L

[0115] Procedure: [0116] 1. Clean and dry the reactor. [0117] 2. Charge Isopropyl alcohol (200 kg) at 25-30 degrees Celsius. [0118] 3. Charge piroctone olamine (100 Kg) at 25-30 degrees Celsius. [0119] 4. Heat the mass to 70 degrees Celsius. [0120] 5. Maintain at 70-75 degrees Celsius for 30 minutes. [0121] 6. Check for dissolution (clear solution should be observed). [0122] 7. If incomplete dissolution, maintain at 70-75 degrees Celsius for another 30 minutes and check for clarity. [0123] 8. At 65-70° C. add 500 g of piroctone olamine crystals for seeding. [0124] 9. Gradually cool the mass to 25-30 degrees Celsius over a period of 3-4 hrs. [0125] 10. Cool the mass to 8-10 degrees Celsius over a period of 2 hours. [0126] 11. Maintain at 8-10 degrees Celsius for 1 hour. [0127] 12. Centrifuge at 8-10 degrees Celsius, wash centrifuge with chilled (at 5-10 degrees Celsius) isopropyl alcohol (wash twice with 37 L). [0128] 13. Spin dry for 30 min. [0129] 14. Unload the wet in to poly bags and weigh the material. [0130] 15. Dry the material in hot air oven below 45 degrees Celsius for 4 hours. [0131] 16. Dry the material at 60 degrees Celsius until 0.3% wt liquid. [0132] 17. 93.0 kg of wet product/91.0 kg dry product was obtained.

[0133] Results

[0134] FIG. 1 illustrates recrystallized crystals of piroctone olamine made according to Example 3, at a magnification of ×200. The image is divided into four for measurement purposes as discussed above and indicates particles whose dimensions have been measured. In total, the w/L of each of 20 particles was measured and the average w/L value was determined. The measurements taken from individual particles are shown. The same procedure had previously been performed on the starting material of piroctone olamine crystals which had not been subject to a recrystallization according to the invention.

[0135] Furthermore, the volumetric distribution density of particles and the volumetric cumulative distribution versus diameter of both the starting and end products were measured as described above and, in each case, d.sub.50 and d.sub.10 were determined. As mentioned above, FIG. 2 illustrates the volumetric distribution density of particles, q (left hand y-axis) and the volumetric cumulative distribution Q(r) (right hand y-axis) versus diameter (x-axis) of particles of piroctone olamine which have not been recrystallized according to the invention, while FIG. 3 illustrates volumetric distribution density of particles, q (left hand y-axis) and the volumetric cumulative distribution Q(r) (right hand y-axis) versus diameter (x-axis) of particles of piroctone olamine made according to Example 3, which have been subject to a recrystallization according to the invention.

[0136] The results were as follows:

TABLE-US-00004 Starting Product End Product (no recrystallization) (recrystallized) d.sub.50 90 145 d.sub.10 45 62 Average w/L 0.23 0.29

[0137] FIG. 4 illustrates a comparison of the time consolidation of recrystallized piroctone olamine (left hand graph) and non-recrystallized piroctone olamine (right hand graph). Both sets of graphs comprise two sets of three measurements: a first set of measurements follows storage at 20 degrees Celsius, 0% relative humidity (rH) and a second set of measurements follows storage at 50 degrees Celsius, 0% relative humidity. Each set comprises three measurements, taken following consolidation after application of a 2 kPa, a 4 kPa and a 12 kPa vertical pressure respectively. The flowability factor, ff.sub.c, discussed above has been measured and is presented in the graphs. The results demonstrate that, under identical storage and consolidation conditions, the recrystallized piroctone olamine is significantly more flowable and therefore less liable to clumping than the non-recrystallized product.

Example 4

[0138] Raw Materials:

TABLE-US-00005 Raw material Quantity Equivalents Piroctone Olamine 100 kg 1.0 Isopropyl alcohol 200 kg 2.74 Two batches of 37 L

[0139] Procedure: [0140] 1. Clean and dry the reactor. [0141] 2. Charge Isopropyl alcohol (200 kg) at 25-30 degrees Celsius. [0142] 3. Charge piroctone olamine (100 Kg) at 25-30 degrees Celsius. [0143] 4. Heat the mass to 70 degrees Celsius. [0144] 5. Maintain at 70-75 degrees Celsius for 30 minutes. [0145] 6. Check for dissolution (clear solution should be observed). [0146] 7. If incomplete dissolution, maintain at 70-75 degrees Celsius for another 30 minutes and check for clarity. [0147] 8. At 65-70° C. add 500 g of piroctone olamine crystals for seeding. [0148] 9. Gradually cool the mass to 25-30 degrees Celsius over a period of 3-4 hrs. [0149] 10. Cool the mass to 8-10 degrees Celsius over a period of 2 hours. [0150] 11. Maintain at 8-10 degrees Celsius for 1 hour. [0151] 12. Centrifuge at 8-10 degrees Celsius, wash centrifuge with chilled (at 5-10 degrees Celsius) isopropyl alcohol (wash twice with 37 L). [0152] 13. Dry the wet filtercake in a cone dryer at a temperature below 45° C., then 1 hour at 60° C. [0153] 14. 92.0 kg of wet product/90.0 kg dry product was obtained.

[0154] Average w/L, d.sub.50 and d.sub.10 were determined as described above. The results were as follows:

TABLE-US-00006 Starting Product End Product (piroctone olamine - (piroctone olamine - no recrystallization) recrystallized) d.sub.50 90 163 d.sub.10 45 69 Average w/L 0.23 0.28

Example 5

[0155] Raw Materials:

TABLE-US-00007 Raw material Quantity Equivalents Piroctone Olamine 150 kg 1.0 Isopropyl alcohol 200 kg 1.8 Two batches of 37 L

[0156] Procedure: [0157] 1. Clean and dry the reactor. [0158] 2. Charge Isopropyl alcohol (200 kg) at 25-30 degrees Celsius. [0159] 3. Charge piroctone olamine (150 Kg) at 25-30 degrees Celsius. [0160] 4. Heat the mass to 70 degrees Celsius. [0161] 5. Maintain at 70-75 degrees Celsius for 1 hr (a white dispersion is formed). [0162] 6. Gradually cool the mass to 25-30 degrees Celsius over a period of 8 hrs. [0163] 7. Cool the mass to 8-10 degrees Celsius over a period of 2 hours. [0164] 8. Maintain at 8-10 degrees Celsius for 1 hour. [0165] 9. Centrifuge at 8-10 degrees Celsius, wash centrifuge with chilled (at 5-10 degrees Celsius) isopropyl alcohol (wash twice with 37 L). [0166] 10. Filter the suspension at 8-10° C. on a filter dryer, with chilled (at 5-10 degrees Celsius) isopropyl alcohol (wash twice with 37 L). [0167] 11. Dry the wet filter cake in a filter dryer at a temperature below 45° C., then 1 hour at 60° C. [0168] 12.154 kg of wet product/144 kg dry product was obtained.

[0169] Average w/L, d.sub.50 and d.sub.10 were determined as described above. The results were as follows:

TABLE-US-00008 Starting Product End Product (piroctone olamine - (piroctone olamine obtained no recrystallization) by the above process) d.sub.50 90 280 d.sub.10 45 82 Average w/L 0.23 0.30