KR101813794B1 - Preparation method for crystallization using rotation disc crystallizer - Google Patents

Preparation method for crystallization using rotation disc crystallizer Download PDF

Info

Publication number
KR101813794B1
KR101813794B1 KR1020160069480A KR20160069480A KR101813794B1 KR 101813794 B1 KR101813794 B1 KR 101813794B1 KR 1020160069480 A KR1020160069480 A KR 1020160069480A KR 20160069480 A KR20160069480 A KR 20160069480A KR 101813794 B1 KR101813794 B1 KR 101813794B1
Authority
KR
South Korea
Prior art keywords
crystallization
rotating
reactor
crystallizer
method according
Prior art date
Application number
KR1020160069480A
Other languages
Korean (ko)
Other versions
KR20170137987A (en
Inventor
김우식
이준화
유태경
Original Assignee
경희대학교 산학협력단
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by 경희대학교 산학협력단 filed Critical 경희대학교 산학협력단
Priority to KR1020160069480A priority Critical patent/KR101813794B1/en
Publication of KR20170137987A publication Critical patent/KR20170137987A/en
Application granted granted Critical
Publication of KR101813794B1 publication Critical patent/KR101813794B1/en

Links

Images

Classifications

    • CCHEMISTRY; METALLURGY
    • C30CRYSTAL GROWTH
    • C30BSINGLE-CRYSTAL-GROWTH; UNIDIRECTIONAL SOLIDIFICATION OF EUTECTIC MATERIAL OR UNIDIRECTIONAL DEMIXING OF EUTECTOID MATERIAL; REFINING BY ZONE-MELTING OF MATERIAL; PRODUCTION OF A HOMOGENEOUS POLYCRYSTALLINE MATERIAL WITH DEFINED STRUCTURE; SINGLE CRYSTALS OR HOMOGENEOUS POLYCRYSTALLINE MATERIAL WITH DEFINED STRUCTURE; AFTER-TREATMENT OF SINGLE CRYSTALS OR A HOMOGENEOUS POLYCRYSTALLINE MATERIAL WITH DEFINED STRUCTURE; APPARATUS THEREFOR
    • C30B15/00Single-crystal growth by pulling from a melt, e.g. Czochralski method
    • C30B15/30Mechanisms for rotating or moving either the melt or the crystal
    • CCHEMISTRY; METALLURGY
    • C30CRYSTAL GROWTH
    • C30BSINGLE-CRYSTAL-GROWTH; UNIDIRECTIONAL SOLIDIFICATION OF EUTECTIC MATERIAL OR UNIDIRECTIONAL DEMIXING OF EUTECTOID MATERIAL; REFINING BY ZONE-MELTING OF MATERIAL; PRODUCTION OF A HOMOGENEOUS POLYCRYSTALLINE MATERIAL WITH DEFINED STRUCTURE; SINGLE CRYSTALS OR HOMOGENEOUS POLYCRYSTALLINE MATERIAL WITH DEFINED STRUCTURE; AFTER-TREATMENT OF SINGLE CRYSTALS OR A HOMOGENEOUS POLYCRYSTALLINE MATERIAL WITH DEFINED STRUCTURE; APPARATUS THEREFOR
    • C30B21/00Unidirectional solidification of eutectic materials
    • C30B21/02Unidirectional solidification of eutectic materials by normal casting or gradient freezing
    • CCHEMISTRY; METALLURGY
    • C30CRYSTAL GROWTH
    • C30BSINGLE-CRYSTAL-GROWTH; UNIDIRECTIONAL SOLIDIFICATION OF EUTECTIC MATERIAL OR UNIDIRECTIONAL DEMIXING OF EUTECTOID MATERIAL; REFINING BY ZONE-MELTING OF MATERIAL; PRODUCTION OF A HOMOGENEOUS POLYCRYSTALLINE MATERIAL WITH DEFINED STRUCTURE; SINGLE CRYSTALS OR HOMOGENEOUS POLYCRYSTALLINE MATERIAL WITH DEFINED STRUCTURE; AFTER-TREATMENT OF SINGLE CRYSTALS OR A HOMOGENEOUS POLYCRYSTALLINE MATERIAL WITH DEFINED STRUCTURE; APPARATUS THEREFOR
    • C30B29/00Single crystals or homogeneous polycrystalline material with defined structure characterised by the material or by their shape

Abstract

The present invention relates to a method of manufacturing a crystallization target material, And rotating the rotary disk device by adjusting the rotation speed and the degree of supersaturation of the crystallization target material, and has an effect of forming stable crystals with high purity in a shorter time.

Description

[0001] The present invention relates to a crystallization method using a rotary disc crystallizer,

The present invention relates to a method for producing crystals using a crystallization apparatus which induces crystallization using a regular flow (vortex) generated around a rotating disk crystallization apparatus.

Crystallization technology is one of the key manufacturing technologies for high value-added industries such as pharmaceuticals, fine chemicals, and materials as well as general-purpose chemical industries such as petrochemicals and foods. Crystallization is a process in which solids precipitate from a homogeneous phase of liquid or gas. . In order for the crystallization to occur, a supersaturated concentration must be produced in a homogeneous solution, the supersaturation concentration becomes the driving force, and solid precipitation occurs by crystallization. Crystallization is classified into reactive crystallization, cold crystallization, evaporation crystallization, and heat addition crystallization depending on the method of making the supersaturated concentration in the solution.

Supersaturation is a state in which the solution contains an amount of solute in an amount exceeding an amount that can be dissolved in a solvent and is in an unstable state in which crystallization phenomenon such as solid precipitation can occur and is maintained in a supersaturated state and stable state The state is called metastable state.

Batch reactors currently used in the crystallization process have technical limitations in that they are expensive to manufacture, have high energy costs, can not produce uniform particles, and have low reproducibility. Further, when the amount of the solvent introduced during the crystallization process is large and the crystal grain size is small or the amorphous phase is left according to the purity, there is a need for a highly efficient crystallization separation process system, to be.

Also, among the preceding studies of the crystallization process, there is a mixed suspension and mixed product removal (MSMPR) reactor which is a continuous stirred tank type reactor. However, in the case of the MSMPR reactor, the size of the particles increases at an increase in the stirring speed in the stirrer, and it may occur locally irregularly in the solution according to the rotation of the stirrer. As a result of the change in the degree of supersaturation of the solvent, There is a problem that the uniformity can not be guaranteed.

Furthermore, conventional crystallization machines use a propeller-type stirrer for flow. In this case, the flow in the crystallizer forms an irregular turbulence. Precise control of the crystallization phenomenon in the existing crystallizer of this flow is very difficult, and crystal formation, growth and phase transition proceed very slowly. The difficulty in controlling the crystallization phenomenon and the slow crystallization rate are deteriorating the process efficiency and deteriorating the quality of the product.

In order to solve these problems, the present inventors have completed a crystallization method for promoting nucleation, growth and phase transition by using a regular flow generated around a rotating disc crystallization apparatus.

Korean Patent Publication No. 2013-0056687

The present invention is intended to provide a crystallization apparatus or a reactor for promoting nucleation, growth and phase transition using a regular flow (vortex) generated around a rotating disk crystallization apparatus.

The present invention also provides a method for producing an efficient and stable crystal by using a crystallization apparatus which generates a regular flow around a rotating disk crystallization apparatus.

In a first aspect of the present invention, there is provided a method of manufacturing a crystallization target material, comprising: introducing a substance to be crystallized into a reactor equipped with a rotating disk crystallization apparatus; And

And rotating the rotating disc crystallization apparatus by adjusting the rotational speed and the supersaturation degree of the crystallization target material (see FIG. 1).

Hereinafter, the present invention will be described in detail.

The rotating disk crystallizing apparatus used in the method of the present invention can be used without limitation as long as it is located in the center of the reactor and vortices of the material to be crystallized are formed in the upper and lower portions of the rotating disk crystallization apparatus. The rotary disc crystallization apparatus may have a rotatable rotary blade.

 In another embodiment, a rotating disc crystallizer used as a conventional reactor can be used in the crystal preparation method of the present invention.

The present invention forms a constant flow or vortex with high intensity over the entire area of the interior of the reactor through rotation of the rotary disk apparatus, so that the crystallization can be carried out by utilizing the phenomenon of promoting the molecular arrangement and mass transfer of the substance of interest 2). That is, the crystal growth due to the self-assembly of the target substance is promoted by the constant flow formed by the rotation of the rotating disk device.

The present invention uses a reactor equipped with a rotating disk crystallization device, thereby exhibiting a very high crystallization efficiency and an even faster crystallization rate. If the flow is made smaller and more uniform, the crystallization process can be further promoted.

In the rotary disk crystallization apparatus, the rotary vane may be in various forms capable of rotating, and in one embodiment may be rod-shaped, spiral or the like. The ratio of the length to width of the rotating blades may be 1 to 1 to 4, but is not limited thereto. In one embodiment, the ratio of the length to width of the rotating blades may be about 1 to 2.4. The length and the length mean the size of the rotating blade portion of the rotating disk crystallization apparatus which occupies the inside of the reactor. It is easy to form a constant flow of intensity that allows the crystallization of the target material, which should be the case when the length of the transverse blade is at least equal to or greater than the length of the longitudinal axis.

In the inside of the reactor, the interval (ΔR in FIG. 2A) between the outer wall of the rotating disk crystallization apparatus and the inner wall of the reactor may be 0.5 to 10% of the total length of the rotating disk crystallization apparatus. In one embodiment, the distance between the outer wall of the rotating disk crystallizer and the inner wall of the reactor may be about 4 mm. If the gap is wide, the flow flow may change.

In the present invention, the substance to be crystallized may be composed of a solvent and a target substance.

The crystallization performance (effect) of the target material may depend on the structure and shape of the crystal. The material to be crystallized of the present invention may be a single crystal or a co-crystal material, and in one embodiment may be a polymorphic material. A polymorph is a polymorphic form when the same molecule, or atom, forms a crystal with three or more different bonds. The polymorph is classified as a thermodynamically low free energy structure and a relatively high structure according to the structure. The former is called the stable phase and the latter is called the metastable phase. When crystals precipitate in supersaturated solution, the metastable phases are first formed according to Ostwald's Rule of Stage and then phase-transformed to ophthalmic phase. The cause of the transition of the two polymorphs is due to the different equilibrium concentrations. That is, the solubility of the stable phase is low, while the solubility of the metastable phase is relatively high.

In the case of the co-crystallization of a polymorph, the solvent is a very important factor. Depending on the kind of the solvent, the polymorph form to be formed may be different, and in some solvents, two forms may be formed at the same time. In one embodiment, the solubility of caffeine is high when the solvent is ethyl acetate.

In another embodiment, the solvent may be at least one selected from the group consisting of water, methanol, ethanol and acetone.

In one embodiment, the substance to be crystallized is selected from the group consisting of sulfamerazine, L-histidine, Sulphathiazole, Piracetam, Tegafur, Carbamazepine, Etiracetam, Cefuroxime Acid, L-Glutamic Acid, Glycine or caffeine-maleate acid.

For example, sulfamerazine (SMZ) is a herbal drug substance in a solid dosage form. It has a metastable phase I and an orthogonal II structure. The phase transition of SMZ proceeds very slowly in the conventional crystallizer, and after 14 days It has been reported that phase transition is not completely achieved. However, when a rotating disk crystallizer using the regular flow of the present invention was used, the phase transition of SMZ form-I crystals to form-II crystals was very rapid, and the phase transition time was greatly reduced. Form-II crystals were also directly formed in the crystallization due to strong regular flow when the disk speed was high.

In the conventional stirrer-type crystallizer, caffeine-maleic acid co-crystals of 2: 1 mole ratio, which is a metastable phase, are precipitated in the co-crystallization of caffeine and maleic acid, Caffeine-maleic acid crystal phase. The phase transformation of the polymorphic crystal requires about 10 hours, but when using the rotating disk crystallization apparatus of the present invention, the caffeine-maleic acid crystal is precipitated as a stable 1: 1 caffeine-maleic acid crystal from the beginning .

The reactor of the present invention may have a plurality of inlets and outlets through which the substance to be crystallized can move into the reactor.

The rotation speed of the rotating disk crystallization apparatus may be from 50 rpm to 1500 rpm. When the rotation speed is less than 50 rpm, there is a problem that the energy dissipation rate is too small, so that a quasi-stable phase of the crystal can be formed and the reaction time may be increased. When the rotation speed exceeds 1500 rpm, the energy consumption increases.

The crystal manufacturing method may further include a step of cooling the reactor after the step of rotating the rotary disk crystallization apparatus, which may be performed through a cooler.

The cooling rate of the reactor may be 20 [deg.] C / h to 35 [deg.] C / h. When the cooling rate is less than 20 캜 / h, the cooling time becomes longer and the total reaction time may become longer. When the cooling rate exceeds 35 캜 / h, both single crystals and co-crystals may be formed at the same time to form impurities .

The initial supersaturation of the target material may be 0.0459 mol / L to 0.0859 mol / L. If the initial supersaturation is less than 0.0459 mol / L, the influx time may become longer and the reaction time may become longer. If the initial supersaturation exceeds 0.0859 mol / L, the caffeine may not be dissolved at the initial preheating temperature have.

The temperature range of the rotary disk crystallizer may be in the range of about 10 캜 to about 30 캜, although it varies depending on the target material. If the temperature is less than 10 ° C, the solubility of the subject materials (eg, caffeine and maleic acid) is too low to monitor the concentration by the ATR-FTIR method and more energy may be consumed to cool the solution. When the temperature exceeds 30 ° C, the solubility of the substance of interest (for example, caffeine and maleic acid) is too high to solidify and may remain as a solution.

In the case of the polymorphic crystal form, it is very important and difficult to produce a thermodynamically stable or desired crystal form continuously. Since each solid form exhibits different physicochemical properties, control over the crystallization of the solid form is important. In addition to the thermodynamic factors (solubility, temperature, solidliquid interfacial tension, etc.) and thermodynamic factors (supersaturation, molecular fluidity, nucleation rate, metastable zone width, etc.) For selective crystallization of the desired crystal form, it must be considered individually and in its entirety.

The crystal preparation method of the present invention can be applied to various fields ranging from new drug / food to energy such as crystal preparation of active drug substance, purification of nucleic acid or amino acid, manufacture of battery electrode material. In other words, it can contribute to high value added products of pharmaceutical, fine chemical and food additive industries.

The method of the present invention can form stable crystals in a high purity in a shorter time by forming a regular flow through a rotating disk crystallizer. Further, it is possible to manufacture a crystal having a desired size by adjusting the rotation speed, cooling rate, flow rate of the target material, type of solvent, temperature range of the apparatus, and the like of the rotary disk crystallizer.

BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a schematic diagram of an apparatus for crystallizing a rotating disk (RD) according to an embodiment of the present invention, and (b) a mixing tank (MT).
FIG. 2 shows a configuration and arrangement of (a) a rotating disk crystallization apparatus according to an embodiment, and (b) and (c) are schematic diagrams of a fluid flow of a rotating disk crystallization apparatus.
Figure 3 shows the analysis of a 1: 1 caffeine / maleic acid co-crystal moiety using Raman spectroscopy, showing (a) relative peak intensity characteristics for pure 2: 1 coarse crystals and 1: 1 coarse crystals And (b) the characteristic peaks of the standard sample by the weight fraction of the two co-crystals.
Figure 4 shows the solubility of 1: 1 caffeine / maleic acid co-crystals in ethyl acetate and at different temperatures according to one embodiment.
Figure 5 shows a directly formed 1: 1 co-crystal, showing (a) the ATR-FTIR measurement result of the corresponding peak area of caffeine and maleic acid, (b) the phase equilibrium diagram, Phase balance.
Fig. 6 shows the results of ATR-FTIR measurements of the corresponding peak areas of caffeine and maleic acid, (b) phase equilibrium (C) shows the estimated phase balance degree.
7 shows the initial supersaturation effect on caffeine and maleic acid co-crystallization in a stirring tank crystallization apparatus, wherein the cooling rate is 20 ° C / h and the stirring speed is 1500 rpm.
8 shows the influence of the initial supersaturation on the stable induction time and the induction temperature in the stirring tank crystallization machine MT and the rotating disk crystallization machine RT and the cooling rate is 20 ° C / , And the stirring speed is 1500 rpm.
9 shows the effect of supersaturation on the reconstruction time in a stirring tank crystallizer, wherein the cooling rate is 20 DEG C / h and the stirring speed is 1500 rpm.
10 shows the effect of stirring / rotation speed on caffeine / maleic acid co-crystals in a stirred tank crystallizer and a rotating disk crystallizer, wherein the cooling rate is 20 ° C / h and the supersaturation is 0.0459 mol / L.
11 shows the influence of the stirring / rotation speed on the stable induction time in the stirring tank crystallizer and the rotating disk crystallizer, wherein the cooling rate is 20 ° C / h and the supersaturation is 0.0459 mol / L.
12 shows the effect of the stirring speed on the reconstruction time in a stirring tank crystallizer, wherein the cooling rate is 1500 rpm and the initial supersaturation is 0.0459 mol / L.
Figure 13 shows the effect of cooling rate on caffeine / maleic acid co-crystallization in a stirred tank crystallizer and a rotating disk crystallizer, with stirring / rotation speeds of 1500 and 250 rpm, respectively, and supersaturation of 0.0459 mol / L.
FIG. 14 shows the effect of cooling rate on the stable induction time in the stirring tank crystallizer and the rotating disk crystallizer, wherein the stirring / rotation speed is 1500 rpm and 250 rpm, and the supersaturation is 0.0459 mol / L.
15 shows the influence of the cooling rate on the rebuild time in a stirring tank crystallizer, the stirring speed is 1500 rpm and the initial supersaturation is 0.0459 mol / L.
16 shows FT-Raman data according to the second embodiment.
FIG. 17 shows a result of determination unit analysis using Raman spectroscopy according to Example 2. FIG.
FIG. 18 shows XRD results according to Example 2, wherein (a) shows an A form and (b) shows a B form.
FIGS. 19 (a) and 19 (b) are top and bottom views of a rotating disc apparatus according to an embodiment, and FIGS. 19 (c) Lt; / RTI >

Hereinafter, the present invention will be described in more detail with reference to Examples. These examples are for further illustrating the present invention, and the scope of the present invention is not limited to these examples.

Example  1: Caffeine / Maleic acid Ball decision

At 45 캜, 0.1 mol / L and 0.3609 mol / L of caffeine and maleic acid, respectively, were dissolved in ethyl acetate to prepare a solution. The following microfilter was used to remove solid impurities and heated to 50 DEG C to dissolve completely. The solution was poured into a reactor equipped with a rotary disk crystallization apparatus having the structure of FIG. 1 and a ratio of FIG. 2, an ATR-FTIR probe and a thermocouple probe, and then the rotation speed of the rotary disk crystallization apparatus was fixed at 100 rpm , And cooled at a cooling rate of 20 占 폚 / h to 50 占 폚 to 25 占 폚 by a chiller. After nucleation, crystals were filtered with a vacuum pump and dried in an oven at 50 ° C. As a result, caffeine / maleic acid co-crystals were formed in a weight ratio of 1: 1 and confirmed by FT-Raman, PXRD, DSC and the like (see FIGS.

Comparative Example  One

The caffeine / maleic acid co-crystal was formed in the same manner as in Example 1 except that a stirring tank crystallization apparatus was used instead of the rotating disk crystallization apparatus. The stirring speed was 1500 rpm. As a result, a 1: 1 weight ratio caffeine / maleic acid crystal was gradually formed over about 10 hours after the 2: 1 caffeine / maleic acid crystal was formed (see FIGS. 7 to 9).

Example 2: L-histidine crystallization

At 50 캜, 0.182 mol / L of L-histidine was dissolved in a mixture of water and ethanol to prepare a solution. The following microfilter was used to remove solid impurities and heated to 55 占 폚 to completely dissolve. The solution was placed in a rotating disk crystallization apparatus having a rotating blade having the structure of FIG. 1 and the ratio of FIG. 2, and then a thermocouple probe was installed in the apparatus. The rotation speed of the wing was fixed at 100 rpm, and the cooling rate was set at 20 캜 / h, and then cooled to 55 캜 and 10 캜 by a chiller. After nucleation, crystals were filtered with a vacuum pump and dried in an oven at 50 ° C. As a result, a stable form of L-histidine was immediately formed, which was confirmed by FT-Raman, XRD, etc. and shown in FIG. 16 to FIG. In FIG. 17, the area ratio on the vertical axis is calculated by using the following equation 1, and the horizontal axis (y) is the A form unit and the following equation 2 is used. In equation 2, x represents the area ratio do.

[Formula 1]

Figure 112016053847536-pat00001

[Formula 2]

y = (x-0.03386) /0.0048

Claims (9)

  1. Introducing a substance to be crystallized into a reactor provided inside the rotating disk crystallizing apparatus rotating around a vertical axis; And
    Rotating the rotating disk crystallizing apparatus by adjusting a rotating speed and a degree of supersaturation of a material to be crystallized;
    Wherein the distance between the outer wall of the rotary blade and the longitudinal inner wall of the reactor in the rotary disk crystallization apparatus is 0.5% to 2% of the length of the rotary disk crystallizer, and the caffeine / ≪ / RTI >
  2. The method according to claim 1,
    Wherein the crystallization target material is composed of a solvent and a target substance.
  3. The method according to claim 1,
    Wherein the rotating disk crystallization apparatus is located at the center of the reactor and a vortex of the crystallization target material is formed in the upper and lower portions of the rotating disk crystallization apparatus.
  4. The method according to claim 1,
    Wherein the supersaturation degree of the substance to be crystallized is 0.0459 mol / L to 0.0859 mol / L.
  5. delete
  6. The method according to claim 1,
    Wherein the rotation speed of the rotary disk crystallizer is 50 rpm to 1500 rpm.
  7. The method according to claim 1,
    The method may further include cooling the reactor after the step of rotating the rotary disk crystallizer, wherein the cooling rate of the reactor is from 20 DEG C / h to 35 DEG C / h, and the caffeine / maleic anhydride ratio of 1: ≪ / RTI >
  8. 3. The method of claim 2,
    Wherein the solvent is at least one selected from the group consisting of water, methanol, ethanol and acetone.
  9. The method according to claim 1,
    Wherein the temperature in the rotating disc crystallizer is in the range of 10 ° C to 30 ° C.
KR1020160069480A 2016-06-03 2016-06-03 Preparation method for crystallization using rotation disc crystallizer KR101813794B1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
KR1020160069480A KR101813794B1 (en) 2016-06-03 2016-06-03 Preparation method for crystallization using rotation disc crystallizer

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
KR1020160069480A KR101813794B1 (en) 2016-06-03 2016-06-03 Preparation method for crystallization using rotation disc crystallizer

Publications (2)

Publication Number Publication Date
KR20170137987A KR20170137987A (en) 2017-12-14
KR101813794B1 true KR101813794B1 (en) 2018-01-02

Family

ID=60954105

Family Applications (1)

Application Number Title Priority Date Filing Date
KR1020160069480A KR101813794B1 (en) 2016-06-03 2016-06-03 Preparation method for crystallization using rotation disc crystallizer

Country Status (1)

Country Link
KR (1) KR101813794B1 (en)

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2004534649A (en) * 2001-07-20 2004-11-18 プロテンシブ リミティッド Method for producing particles

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2004534649A (en) * 2001-07-20 2004-11-18 プロテンシブ リミティッド Method for producing particles

Also Published As

Publication number Publication date
KR20170137987A (en) 2017-12-14

Similar Documents

Publication Publication Date Title
US6558435B2 (en) Reactive crystallization method to improve particle size
CN100540533C (en) Crystalline forms of optical enantiomers of modafinil and method for the production
Beckmann Seeding the desired polymorph: background, possibilities, limitations, and case studies
Ulrich et al. Crystallization
Lorenz et al. Crystallization of enantiomers
US5314506A (en) Crystallization method to improve crystal structure and size
EP0097405B1 (en) Apparatus for concentrating a suspension
JP2508949B2 (en) N- (trans-4-isopropylcyclohexylcarbonyl)-d-crystalline and preparation of phenylalanine
Sato Polymorphic transformations in crystal growth
Garti et al. The effect of surfactants on the crystallization and polymorphic transformation of glutamic acid
ES2632499T3 (en) Process for preparing sterile aripiprazole of desired average particle size
JP4876208B2 (en) Apparatus and method for crystallization by hydrodynamic cavitation
Eder et al. Seed loading effects on the mean crystal size of acetylsalicylic acid in a continuous‐flow crystallization device
Benmore et al. Amorphization of molecular liquids of pharmaceutical drugs by acoustic levitation
TW200925152A (en) Processes for the preparation of crystalline forms A, B and pure crystalline form a of erlotinib HCL
CN1058540A (en) Process and equipment for crystallising inorganic substance
JP2006117441A (en) Method for preparing silicon carbide single crystal
JP5295190B2 (en) Method for crystallization of reverse transcriptase inhibitor using reverse solvent
Wermester et al. Preferential crystallization in an unusual case of conglomerate with partial solid solutions
Ni et al. Effects of mixing, seeding, material of baffles and final temperature on solution crystallization of l-glutamic acid in an oscillatory baffled crystallizer
Veesler et al. Crystallization in the presence of a liquid− liquid phase separation
Cesur et al. Crystallization of mefenamic acid and polymorphs
US3645699A (en) Solid-liquid continuous countercurrent purifier method and apparatus
US4127597A (en) Continuous fractionation of tallow and production of a cocoa butter-like plastic fat
CN104471118B (en) SiC single crystal ingot and its manufacture method

Legal Events

Date Code Title Description
AMND Amendment
AMND Amendment
X701 Decision to grant (after re-examination)
GRNT Written decision to grant