Piroctone olamine recrystallization

Abstract

The present invention relates to a piroctone olamine recrystallization method, a piroctone olamine crystal preparation method and piroctone olamine crystals obtainable by these methods.

Description

[0001] The present invention relates to a recrystallization method of piroctone olamine and piroctone olamine crystals obtainable therefrom. The present invention further relates to a preparation method of piroctone olamine crystals and piroctone olamine crystals obtainable therefrom.

[0002] With reference to DE 2 234 009 A1 and DE 1 795 270 A1, 1-hydroxy-4-methyl-6-(2,4,4-trimethyl)-pentyl-2(1H)-pyridone, 2-aminoethanol salt (also known as piroctone olamine) is an antifungal active agent effective against the causes of dandruff. It is known to include piroctone olamine in personal care products, such as shampoos. DE 1 795 270 A1 also describes a process for preparing piroctone olamine.

[0003] Piroctone olamine exists in crystalline form that can be added to personal care products. Commercially available piroctone olamine prepared by methods such as those described above typically has a width / length ratio of approximately 1:7 and a median diameter (d 50 ) is about 100 microns of primary crystals. Primary crystals are those formed during the crystallization process, but before further processing and batch processing steps. After such large batches of further processing and treatment, the crystals may change size. Such large batches of piroctone olamine crystals may gather together to form agglomerates. When handling and processing large batches of crystals, caking may cause difficulties.

[0004] CN 1907971 A relates to a method for producing the antifungal material ciclopirox ethanolamine. The document discusses recrystallization but does not discuss the agglomeration problem.

[0005] It is in this context that the present invention is designed.

[0006] In this document, including in all embodiments of all aspects of the invention, the following definitions apply unless specifically stated otherwise.

[0007] Regarding the particle size distribution measurement used here, d 50 , d(50) or D50, the median value, is defined as the diameter at which half of the total population of particles lies below that value. Similarly, 10% of the total population of particles lies below d 10 , d(10) or less than D10 diameter.

[0008] All percentages are by weight of the total composition (w / w). All ratios are by weight. "wt.%" means percentage by weight. The so-called "parts", for example, a mixture of 1 part X and 3 parts Y is a weight ratio. "QS" or "QSP" means the amount sufficient for 100% or 100g. + / - indicates standard deviation. All ranges are inclusive and combinable. The number of significant figures conveys no limitation on the accuracy of the amounts shown nor on the measurements. All numerical quantities are to be understood as being modified by the word "approximately". All measurements are to be understood as being made at 23°C and under ambient conditions, where "ambient conditions" means at 1 atmosphere of pressure (atm) and 50% relative humidity. "Relative humidity" refers to the ratio (given as a percentage) of the moisture content of the air compared to the saturation humidity level at the same temperature and pressure. Relative humidity can be measured using a hygrometer, especially one obtained from International's probe moisture meter measurement. Here "min" means "minute". Here "mol" means mole. Here "g" after the quantity means "gram", and "kg" means "kilogram". Here "comprising" means that there may be other steps and other ingredients in addition. The embodiments and aspects described herein may include or may be combined with elements, features or components of other embodiments and / or aspects that are not explicitly exemplified in combination, unless it is indicated that they are not compatible. "In at least one embodiment" means that one or more embodiments of the present invention, optionally all embodiments or most embodiments have the characteristics described subsequently. "Molecular weight" or "M.Wt." or "MW" and grammatical equivalents refer to number-average molecular weight.

[0009] According to a first aspect of the present invention, there is provided a method for recrystallizing piroctone olamine, comprising:

[0010] a) dissolving piroctone olamine in an alcoholic solvent, wherein the dissolution is carried out at a dissolution temperature, which is a temperature greater than 50 degrees Celsius and less than the boiling point of the alcohol;

[0011] b) cooling the solution from the dissolution temperature to a temperature of 1-15 degrees Celsius for a period of up to 10 hours, preferably 10 minutes to 10 hours, more preferably 1-7 hours, even more preferably 1-5 hours;

[0012] c) recovering the crystals of piroctone olamine.

[0013] According to a second aspect of the present invention, there is provided a method for preparing piroctone olamine crystals, comprising:

[0014] a) dispersing piroctone olamine in an alcoholic solvent, wherein the dispersing is carried out at a dispersing temperature, which is a temperature greater than 50 degrees Celsius and less than the boiling point of the alcohol;

[0015] b) cooling the dispersion from the dispersion temperature to a temperature of 1 to 15 degrees Celsius for a period of up to 15 hours, preferably 10 minutes to 15 hours, more preferably 1 to 12 hours;

[0016] c) recovering the crystals of piroctone olamine.

[0017] The recrystallization method of the first aspect of the present invention and the preparation method of the second aspect of the present invention produce crystals with different sizes from the crystals of the starting product. Surprisingly, a large number of these crystals of different sizes are observed to be less prone to agglomeration. These crystals are the subject of the third aspect of the present invention.

[0018] According to the first aspect of the present invention, 1.5-4 kg, preferably 2 kg, of solvent is used per kilogram of piroctone olamine.

[0019] In a specific embodiment, crystals of piroctone olamine are added to seed. Those skilled in the art are aware of the concept of seeding / using seeds. Preferably, crystals of piroctone olamine for seeding are added after step a). Also preferably, crystals of piroctone olamine for seeding are added before or during step b). Preferably, crystals of piroctone olamine for seeding are added in an amount of 0.1-3.0wt%, more preferably 0.3-1.0wt%, and particularly preferably 0.5wt%, based on the amount of piroctone olamine used in step a).

[0020] According to a first aspect of the invention, cooling can be performed in two steps:

[0021] i. in a first cooling step, cooling the solution from the dissolution temperature to a temperature of 20-40 degrees Celsius for a first cooling period of up to 5 hours;

[0022] ii. In a second cooling step, the solution is cooled from a temperature of 20-40 degrees Celsius to a temperature of 1-15 degrees Celsius for a second cooling period of up to 5 hours. Preferably, the second cooling period lasts 3 hours or less.

[0023] The alcohol contained in the solvent is selected from methanol, ethanol, propanol, isopropanol, n-butanol, isobutanol and mixtures thereof. Preferably, the alcohol comprises isopropanol.

[0024] The solvent may also include ethyl acetate, isopropyl acetate, butyl acetate, dichloromethane, chloroform, n-hexane, benzene, toluene, acetone, butanone, diisopropyl ether, methyl tert-butyl ether, tetrahydrofuran, diisopropyl ether ... Alkanes and mixtures thereof.

[0025] Advantageously, the solvent comprises 50% wt or more, preferably 90% wt or more, of alcohol. More preferably, the solvent consists of alcohol. Still more preferably, the solvent consists of isopropanol.

[0026] According to a first aspect of the present invention, in a), the dissolution temperature is 60-82.5 degrees Celsius, preferably 70-75 degrees Celsius. In addition, the mixture of piroctone olamine and solvent is maintained at the dissolution temperature until the piroctone olamine is completely dissolved in the solvent. A transparent solution indicates complete dissolution.

[0027] According to the second aspect of the present invention, 1-3 kg, preferably 1.0-1.5 kg, more preferably 1.2-1.4 kg, particularly preferably 1.33 kg of solvent is used per kilogram of piroctone olamine.

[0028] In a specific embodiment, crystals of piroctone olamine are added to seed. Preferably, crystals of piroctone olamine for seeding are added after step a). Also preferably, crystals of piroctone olamine for seeding are added before or during step b). Preferably, crystals of piroctone olamine for seeding are added in an amount of 0.1-3.0wt%, more preferably 0.3-1.0wt%, particularly preferably 0.5wt%, based on the amount of piroctone olamine used in step a).

[0029] According to a second aspect of the invention, cooling can be performed in two steps:

[0030] i. in a first cooling step, cooling the dispersion from the dispersion temperature to a temperature of 20-40 degrees Celsius for a first cooling period of up to 10 hours;

[0031] ii. In a second cooling step, the dispersion is cooled from a temperature of 20-40 degrees Celsius to a temperature of 1-15 degrees Celsius for a second cooling period of up to 5 hours. Preferably, the second cooling period lasts 3 hours or less.

[0032] The alcohol contained in the solvent is selected from methanol, ethanol, propanol, isopropanol, n-butanol, isobutanol and mixtures thereof. Preferably, the alcohol comprises isopropanol.

[0033] The solvent may also include ethyl acetate, isopropyl acetate, butyl acetate, dichloromethane, chloroform, n-hexane, benzene, toluene, acetone, butanone, diisopropyl ether, methyl tert-butyl ether, tetrahydrofuran, diisopropyl ether ... Alkanes and mixtures thereof.

[0034] Advantageously, the solvent comprises 50% wt or more, preferably 90% wt or more, of alcohol. More preferably, the solvent consists of alcohol. Still more preferably, the solvent consists of isopropanol.

[0035] According to the second aspect of the present invention, in a), the dispersion temperature is 60-82.5 degrees Celsius, preferably 70-75 degrees Celsius.

[0036] According to a third aspect of the present invention, there is provided piroctone olamine crystals having an average width-to-length ratio greater than 1:4.

[0037] For the sake of completeness, since a ratio is being referenced, by saying that the ratio is "greater than" a certain value, it is meant that the second number (after the colon) is less than the number given, ie, less than "4" in the present case.

[0038] As mentioned above, commercially available piroctone olamine prepared by methods such as those described above typically has primary crystals with a width / length ratio of about 1:7. Primary crystals are those formed during the crystallization process, but before further processing and batch handling steps. During such processing and batch handling steps, the brittle primary crystals may change shape, but their average width / length is found to be significantly less than 1:4. As explained, crystals of this size may suffer from agglomeration in large quantities.

[0039] Preferably, the piroctone olamine crystals have an average width-to-length ratio greater than 1:4 and less than 1:2.

[0040] In a preferred embodiment of the third aspect of the invention, the piroctone olamine crystals have a d greater than 110 microns, preferably greater than 140 microns. 50 In a more preferred embodiment, the piroctone olamine crystals have a d greater than 30 microns, preferably greater than 50 microns. 10 .

[0041] Preferably, the piroctone olamine crystals have a d value greater than 110 microns and less than 400 microns. 50 More preferably, the piroctone olamine crystals have a d greater than 140 microns and less than 350 microns. 50 Even more preferably, the piroctone olamine crystals have a d greater than 140 microns and less than 300 microns. 50 .

[0042] In a preferred embodiment, the piroctone olamine crystals have a d greater than 170 microns and less than 350 microns. 50 In a particularly preferred embodiment, the piroctone olamine crystals have a d 50 .

[0043] Preferably, the piroctone olamine crystals have a d greater than 30 microns and less than 120 microns. 10 More preferably, the piroctone olamine crystals have a d greater than 50 microns and less than 100 microns.10 In a particularly preferred embodiment, the piroctone olamine crystals have a d 10 .

[0044] Preferably, the piroctone olamine crystals are obtainable by the piroctone olamine recrystallization method defined herein.

[0045] Preferably, the piroctone olamine crystals are obtainable by the method for preparing piroctone olamine crystals as defined herein.

[0046] The present invention further relates to piroctone olamine crystals obtainable by the process for recrystallization of piroctone olamine as defined herein.

[0047] The present invention further relates to piroctone olamine crystals obtainable by the process for the preparation of piroctone olamine crystals as defined herein.

[0048] The present invention will now be further described with reference to the accompanying drawings, in which:

[0049] Figure 1 A microscope image of some recrystallized piroctone olamine crystals is shown, divided into four sections using a crosshair ruler in preparation for width and length measurements in the manner described below.

[0050] Figure 2 The volume distribution density q (left-hand y-axis) and the volume cumulative distribution Q(r) (right-hand y-axis) of the particles are shown versus the diameter (x-axis) of piroctone olamine particles which have not been recrystallized according to the invention.

[0051] Figure 3 The volume distribution density q (left-hand y-axis) and the volume cumulative distribution Q(r) (right-hand y-axis) of the particles are shown versus the diameter (x-axis) of the piroctone olamine particles according to Example 3 (which have been subjected to recrystallization according to the invention).

[0052] Figure 4 A comparison of the time consolidation of piroctone olamine recrystallized using the process of the present invention (left hand graph) and non-recrystallized piroctone olamine (right hand graph) is shown.

[0053] Particle size distribution measurement method

[0054] The diameter, volume distribution density and volume cumulative distribution of the product were measured using a Horiba LA-950 particle size analyzer. The analyzer uses a laser diffraction method (ISO 13320:2009, Fraunhofer diffraction method) to measure the distribution, and is based on the proportional relationship between the light intensity scattered by the particles and the diameter. In addition, the scattering angle is inversely proportional to the diameter, and vice versa.

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

[0056] Add the required amount of sieved product to the trough of the dry dispersion unit.

[0057] Three measurements were performed in a HORIBA LA-950 particle size analyzer using the following parameters:

[0058] · Slot start value 85-110 (no unit), automatic control

[0059] Dispersion pressure: 0.3MPa.

[0060] The three measurements are combined with the software to form an average measurement. The focus of the analysis is based on d 10 and d 50 Volume fraction.

[0061] Measuring the width / length ratio of piroctone olamine crystals

[0062] Use a spatula to spread a small amount of the sieved product (see above) onto a Petri dish.

[0063] Under the microscope, look for locations where isolated particles are clearly visible. The microscope used is a Keyence VHX2000 series digital microscope equipped with a VH-Z20W zoom lens, using a VHX-S90BE free angle observation system. The microscope does not form part of the present invention, and the technician can choose a suitable alternative microscope.

[0064] Set limits for the depth of field and set up the image using the depth of field function of the microscope at the appropriate magnification.

[0065] The photographs were taken at the following magnifications x50, x100, 150, x200 to get a general impression of the massive crystals.

[0066] A position is required on the Petri dish in which a 3×3 image area can be produced with as many individual particles as possible.

[0067] Take 3x3 images at a magnification of x200.

[0068] The image was divided into 4 sections using a crosshair scale. Five representative particles were selected in each quarter (20 particles in total). For each of these 20 particles, the width (w) and length (L) as well as the w / L ratio were determined. The average w / L ratio of all particles was then calculated, which is the sum of the measured w / L divided by the number of particles ((Σw / L) / 20).

[0069] Flowability Measurement

[0070] Agglomeration of crystals can be considered as a low degree of fluidity. Therefore, in order to obtain an objective measure of agglomeration, the fluidity of the crystals can be measured. The skilled person will be aware of other ways to characterize agglomeration.

[0071] The fluidity of a bulk solid can be determined by its unrestrained yield strength σ c The unrestricted yield strength depends on the consolidation stress σ1 and the storage period t. c The ratio of ff c Used to numerically characterize fluidity:

[0072] ff c＝ σ 1 / σ c

[0073] ff c The larger the unrestricted yield strength σ c The smaller the ratio to the consolidation stress σ1, the better the bulk solid flows. The flow behavior is defined as follows:

[0074] ff c Less than 1, no flow

[0075] ff c 1 to less than 2, very sticky

[0076] ff c 2 to less than 4, sticky

[0077] ff c 4 to less than 10, easy to flow

[0078] ff c Greater than 10, free flowing.

[0079] Parameter ff c It can be produced using a ring shear test in the manner described by Schulze, D (2009) "Pulver und Schüttgüter", 2nd edition, Springer, Berlin. This method does not form part of the present invention and is only mentioned as a way to characterize flowability in order to demonstrate the influence of the easier flow properties of the recrystallized crystals according to the present invention. The skilled person will know other ways to characterize flowability.

[0080] Laboratory Synthesis Example

[0081] Example 1

[0082] Raw materials:

[0083]

[0084] program:

[0085] 1. Clean and dry the reactor.

[0086] 2. Feed ethanol (200 kg) at 25-30 degrees Celsius.

[0087] 3. Feed Piroctone olamine (100 kg) at 25-30 degrees Celsius.

[0088] 4. Heat the substance to 70 degrees Celsius.

[0089] 5. Maintain at 70-75 degrees Celsius for 30 minutes.

[0090] 6. Check for dissolution (a clear solution should be observed).

[0091] 7. If not completely dissolved, maintain at 70-75 degrees Celsius for another 30 minutes and check for clarity.

[0092] 8. The material was gradually cooled to 25-30 degrees Celsius over a period of 3-4 hours.

[0093] 9. Cool the mass to 8-10 degrees Celsius over a period of 2 hours.

[0094] 10. Maintain at 8-10 degrees Celsius for 1 hour.

[0095] 11. Centrifuge at 8-10 degrees Celsius and wash the centrifuge with cold (at 5-10 degrees Celsius) ethanol (wash twice with 37L).

[0096] 12. Spin dry for 30 minutes.

[0097] 13. Unload the wet material into poly bags and weigh the material.

[0098] 14. Dry the material in a hot air oven below 45 degrees Celsius for 4 hours.

[0099] 15. Dry the material at 60 degrees Celsius until 0.3% wt liquid.

[0100] 16. Obtained 79.1 kg wet product / 77.4 kg dry product.

[0101] Example 2

[0102] Raw materials:

[0103]

[0104] program:

[0105] 1. Clean and dry the reactor.

[0106] 2. Feed isopropanol (200 kg) at 25-30 degrees Celsius.

[0107] 3. Feed Piroctone olamine (100 kg) at 25-30 degrees Celsius.

[0108] 4. Heat the substance to 70 degrees Celsius.

[0109] 5. Maintain at 70-75 degrees Celsius for 30 minutes.

[0110] 6. Check for dissolution (a clear solution should be observed).

[0111] 7. If not completely dissolved, maintain at 70-75 degrees Celsius for another 30 minutes and check for clarity.

[0112] 8. The mass was gradually cooled to 8-10°C over a period of 4-5 hours.

[0113] 9. Maintain at 8-10 degrees Celsius for 1 hour.

[0114] 10. Centrifuge at 8-10 degrees Celsius and wash the centrifuge with cold (at 5-10 degrees Celsius) isopropanol (wash twice with 37L).

[0115] 11. Spin dry for 30 minutes.

[0116] 12. Unload the wet material into plastic bags and weigh the material.

[0117] 13. Dry the material in a hot air oven below 45 degrees Celsius for 4 hours.

[0118] 14. Dry the material at 60 degrees Celsius until 0.3% wt liquid.

[0119] 15. Obtained 92.5 kg wet product / 90.5 kg dry product.

[0120] Example 3

[0121] Raw materials:

[0122]

[0123] program:

[0124] 1. Clean and dry the reactor.

[0125] 2. Feed isopropanol (200 kg) at 25-30 degrees Celsius.

[0126] 3. Feed Piroctone olamine (100 kg) at 25-30 degrees Celsius.

[0127] 4. Heat the substance to 70 degrees Celsius.

[0128] 5. Maintain at 70-75 degrees Celsius for 30 minutes.

[0129] 6. Check for dissolution (a clear solution should be observed).

[0130] 7. If not completely dissolved, maintain at 70-75 degrees Celsius for another 30 minutes and check for clarity.

[0131] 8. At 65-70°C, add 500 g of piroctone olamine crystals for seeding.

[0132] 9. The material was gradually cooled to 25-30 degrees Celsius over a period of 3-4 hours.

[0133] 10. Cool the mass to 8-10 degrees Celsius over a period of 2 hours.

[0134] 11. Maintain at 8-10 degrees Celsius for 1 hour.

[0135] 12. Centrifuge at 8-10 degrees Celsius and wash the centrifuge with cold (at 5-10 degrees Celsius) isopropanol (wash twice with 37L).

[0136] 13. Spin dry for 30 minutes.

[0137] 14. Unload the wet material into plastic bags and weigh the material.

[0138] 15. Dry the material in a hot air oven below 45 degrees Celsius for 4 hours.

[0139] 16. Dry the material at 60 degrees Celsius until 0.3% wt liquid.

[0140] 17. Obtained 93.0 kg wet product / 91.0 kg dry product.

[0141] result

[0142] Figure 1 The recrystallized crystals of piroctone olamine prepared according to Example 3 are shown at a magnification of x200. For the above-mentioned measurement purpose, the image is divided into four parts, and indicates the particles whose size has been measured. The w / L of each of 20 particles has been measured in total, and the average w / L value has been determined. The measured value obtained from the individual particles has been shown. The starting material of the piroctone olamine crystals not recrystallized according to the present invention is carried out the same procedure in advance.

[0143] Furthermore, the volume distribution density and the volume cumulative distribution of the particles were measured as described above in relation to the diameter of the starting and final product and d 50 and d 10 As mentioned above, Figure 2The volume distribution density q (left-hand y-axis) and the volume cumulative distribution Q(r) (right-hand y-axis) of the particles are shown relative to the diameter (x-axis) of the piroctone olamine particles not recrystallized according to the present invention, while Figure 3 The volume distribution density q (left-hand y-axis) and the volume cumulative distribution Q(r) (right-hand y-axis) of the particles are shown relative to the diameter (x-axis) of the piroctone olamine particles according to Example 3 (which have been subjected to recrystallization according to the invention).

[0144] The results are as follows:

[0145]

[0146] Figure 4 Shown is a comparison of the time consolidation of recrystallized piroctone olamine (left hand graph) and unrecrystallized piroctone olamine (right hand graph). Both sets of graphs contain two groups of three measurements: the first set of measurements was performed after storage at 20 degrees Celsius and 0% relative humidity (rH), and the second set of measurements was performed after storage at 50 degrees Celsius and 0% relative humidity. Each group includes three measurements, taken after consolidation after applying 2 kPa, 4 kPa and 12 kPa vertical pressures, respectively. The flowability factor discussed above c has been measured and is presented in the figure. The results show that under the same storage and consolidation conditions, the recrystallized piroctone olamine is more flowable and therefore less prone to agglomeration than the non-recrystallized product.

[0147] Example 4

[0148] Raw materials:

[0149]

[0150] program:

[0151] 1. Clean and dry the reactor.

[0152] 2. Feed isopropanol (200 kg) at 25-30 degrees Celsius.

[0153] 3. Feed Piroctone olamine (100 kg) at 25-30 degrees Celsius.

[0154] 4. Heat the substance to 70 degrees Celsius.

[0155] 5. Maintain at 70-75 degrees Celsius for 30 minutes.

[0156] 6. Check for dissolution (a clear solution should be observed).

[0157] 7. If not completely dissolved, maintain at 70-75 degrees Celsius for another 30 minutes and check for clarity.

[0158] 8. At 65-70°C, add 500 g of piroctone olamine crystals for seeding.

[0159] 9. The material was gradually cooled to 25-30 degrees Celsius over a period of 3-4 hours.

[0160] 10. Cool the mass to 8-10 degrees Celsius over a period of 2 hours.

[0161] 11. Maintain at 8-10 degrees Celsius for 1 hour.

[0162] 12. Centrifuge at 8-10 degrees Celsius and wash the centrifuge with cold (at 5-10 degrees Celsius) isopropanol (wash twice with 37L).

[0163] 13. Dry the wet cake in a conical dryer at a temperature below 45°C and then at 60°C for 1 hour.

[0164] 14. Obtained 92.0 kg wet product / 90.0 kg dry product.

[0165] The average w / L, d 50 and d 10 The results are as follows:

[0166]

[0167] Example 5

[0168] Raw materials:

[0169]

[0170] program:

[0171] 1. Clean and dry the reactor.

[0172] 2. Feed isopropanol (200 kg) at 25-30 degrees Celsius.

[0173] 3. Feed Piroctone olamine (150 kg) at 25-30 degrees Celsius.

[0174] 4. Heat the substance to 70 degrees Celsius.

[0175] 5. Maintain at 70-75 degrees Celsius for 1 hour (a white dispersion is formed).

[0176] 6. The material was gradually cooled to 25-30 degrees Celsius over a period of 8 hours.

[0177] 7. Cool the mass to 8-10 degrees Celsius over a period of 2 hours.

[0178] 8. Maintain at 8-10 degrees Celsius for 1 hour.

[0179] 9. Centrifuge at 8-10 degrees Celsius and wash the centrifuge with cold (at 5-10 degrees Celsius) isopropanol (wash twice with 37L).

[0180] 10. Filter the suspension on a filter dryer at 8-10°C and wash with cold (at 5-10 degrees Celsius) isopropanol (two times with 37 L).

[0181] 11. Dry the wet cake in a filter dryer at a temperature below 45°C and then at 60°C for 1 hour.

[0182] 12. Obtained 154 kg wet product / 144 kg dry product.

[0183] The average w / L, d 50 and d 10 The results are as follows:

[0184]

Claims

1. A method for recrystallizing piroctone olamine, comprising: a) dissolving piroctone olamine in an alcoholic solvent, wherein the dissolution is carried out at a dissolution temperature, which is a temperature greater than 50 degrees Celsius and less than the boiling point of the alcohol, wherein the solvent contains 90%wt or more of the alcohol, and wherein the alcohol contained in the solvent is selected from ethanol, isopropanol and mixtures thereof; b) cooling the solution from the dissolution temperature to a temperature of 1-15 degrees Celsius for a period of up to 10 hours; c) recovering the crystals of piroctone olamine.

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

3. The process of claim 1 or 2, wherein crystals of piroctone olamine are added for seeding.

4. The method of claim 1 or 2, wherein cooling is carried out in two steps: i. In a first cooling step, the solution is cooled from the dissolution temperature to a temperature of 20-40 degrees Celsius for a first cooling period of up to 5 hours; ii. In a second cooling step, the solution is cooled from a temperature of 20-40 degrees Celsius to a temperature of 1-15 degrees Celsius for a second cooling period of up to 5 hours.

5. The method of claim 1 or 2, wherein the alcohol comprises isopropanol.

6. The method of claim 1 or 2, wherein the solvent consists of an alcohol.

7. The method of claim 1 or 2, wherein the solvent consists of isopropanol.

8. The method of claim 1 or 2, wherein the dissolution temperature is 60-82.5 degrees Celsius.

9. A method for preparing piroctone olamine crystals, comprising: a) dispersing piroctone olamine in an alcoholic solvent, wherein the dispersion is carried out at a dispersion temperature, which is a temperature greater than 50 degrees Celsius and less than the boiling point of the alcohol, wherein the solvent contains 90%wt or more of the alcohol, and wherein the alcohol contained in the solvent is selected from ethanol, isopropanol and mixtures thereof; b) cooling the dispersion from the dispersion temperature to a temperature of 1 to 15 degrees Celsius for a period of up to 15 hours; c) recovering the crystals of piroctone olamine.

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

11. The method of claim 9 or 10, wherein cooling is carried out in two steps: i. in a first cooling step, cooling the dispersion from the dispersion temperature to a temperature of 20-40 degrees Celsius for a first cooling period of up to 10 hours; ii. In a second cooling step, the dispersion is cooled from a temperature of 20-40 degrees Celsius to a temperature of 1-15 degrees Celsius for a second cooling period of up to 5 hours.

12. The method of claim 9 or 10, wherein the alcohol comprises isopropanol.

13. The method of claim 9 or 10, wherein the solvent consists of an alcohol.

14. The method of claim 9 or 10, wherein the solvent consists of isopropanol.

15. The method of claim 9 or 10, wherein the dispersion temperature is 60-82.5 degrees Celsius.

16. Piroctone olamine crystals having an average width-to-length ratio greater than 1:4, obtained by the process defined in any one of claims 1 to 15.

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

18. The piroctone olamine crystal of claim 16, having a d greater than 30 microns. 10 .

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