CN111825662A - Dantrolene sodium crystal form and preparation method thereof - Google Patents
Dantrolene sodium crystal form and preparation method thereof Download PDFInfo
- Publication number
- CN111825662A CN111825662A CN202010310215.9A CN202010310215A CN111825662A CN 111825662 A CN111825662 A CN 111825662A CN 202010310215 A CN202010310215 A CN 202010310215A CN 111825662 A CN111825662 A CN 111825662A
- Authority
- CN
- China
- Prior art keywords
- dantrolene sodium
- crystal form
- dantrolene
- preparation
- degrees
- Prior art date
- Legal status (The legal status 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 status listed.)
- Pending
Links
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/02—Muscle relaxants, e.g. for tetanus or cramps
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pain & Pain Management (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Neurology (AREA)
- Physical Education & Sports Medicine (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
The invention discloses a dantrolene sodium crystal form A and a preparation method thereof. The dantrolene sodium crystal form A provided by the invention has high purity, low impurity content, simple operation, mild reaction conditions, easy control, and capability of obtaining a target product crystal form with very definite and good reproducibility.
Description
The present application claims priority from a chinese patent application entitled "a crystal form of dantrolene sodium and a method for preparing the same" filed by the chinese patent office on 18/4/2019 with application number 201910313705.1, the entire contents of which are incorporated herein by reference.
Technical Field
The invention belongs to the technical field of medicines, relates to a dantrolene sodium crystal form A, and further relates to a preparation method of the dantrolene sodium crystal form A.
Background
Dantrolene sodium has a chemical name of 1- [ [ [5- (4-nitrophenyl) -2-furyl ] methylene ] amino ] -2, 4-imidazolidinedione sodium salt 3.5 crystal water and has a chemical structural formula as follows:
danqulin sodium English name Dantrolene sodium was approved in 1974 in the United states for marketing, and the former company keeps the United states clean (P)&G) In that respect Dantrolene sodium is approved for the treatment of malignant hyperthermia. Malignant Hyperthermia (MH) is a severe syndrome of hypermetabolism of skeletal muscles, which occurs mainly by Ca in skeletal muscle cells2+Increase in concentration and then yieldLethal hypermetabolic crisis. Eventually leading to the death of the patient. Dantrolene sodium is a muscle relaxant directly acting on skeletal muscle, and can inhibit muscle contraction by inhibiting the release of calcium ions from sarcoplasmic reticulum in the skeletal muscle, thereby treating malignant hyperpyrexia. Data show that dantrolene sodium can reduce the fatality rate of patients from 100% to 5% -10%. Since the incidence rate of malignant hyperpyrexia is not high, but the death rate is high without specific drugs, the disease belongs to a rare disease, and dantrolene sodium is called as an orphan drug which is a rare disease drug.
The dantrolene sodium sold in the market at present is mainly a capsule, and a small part of the dantrolene sodium is an injection, and a dantrolene sodium crystal form is disclosed in a patent with the patent number of CN102302461, and the crystal form is unstable, so that a new crystal form with high stability needs to be developed.
Disclosure of Invention
An object of the present invention is to provide dantrolene sodium form a.
It is another object of the present invention to provide a process for preparing the above dantrolene sodium form a.
The crystal form A of dantrolene sodium is a crystal hydrate, and the structural formula of the crystal form A is shown as the formula (I):
in one aspect, the invention provides a crystal of a compound represented by formula (I), wherein form a has characteristic absorption peaks at 8.3 ± 0.2 °, 11.0 ± 0.2 °, 12.4 ± 0.2 °, 16.6 ± 0.2 °, 27.3 ± 0.2 ° using Cu-Ka radiation by X-ray powder diffraction at an angle of 2 θ.
Specifically, the crystal form A has characteristic absorption peaks at 4.0 +/-0.2 °, 8.3 +/-0.2 °, 11.0 +/-0.2 °, 12.4 +/-0.2 °, 15.2 +/-0.2 °, 16.6 +/-0.2 °, 19.2 +/-0.2 °, 20.9 +/-0.2 °, 22.2 +/-0.2 °, 23.5 +/-0.2 °, 25.9 +/-0.2 ° and 27.3 +/-0.2 ° by X-ray powder diffraction expressed by using Cu-Ka radiation and 2 theta angles.
More specifically, the X-ray powder diffraction represented by 2 theta angle is carried out by using Cu-Ka radiation, and the diffraction peak of the crystal form A is shown in the attached figure 1 in the specification.
Specifically, the differential scanning thermal analysis of the crystal form A is shown in the attached figure 2 in the specification.
Specifically, the thermogravimetric analysis of the crystal form A is shown in the attached figure 3 in the specification.
In another aspect, the present invention provides a process for preparing the above dantrolene sodium form a, said process comprising the steps of:
step 1) adding a dantrolene sodium crude product into a methanol solution, controlling the temperature to be 20-30 ℃, stirring, and filtering under reduced pressure;
and 2) drying the product obtained in the step 1) in vacuum to obtain the dantrolene sodium crystal form A.
Specifically, the concentration of the methanol in the step 1) is 50-100% (v/v), and the stirring time is 6-16 hours.
Specifically, in the step 2), the drying temperature is 40-50 ℃, and the drying time is 36-48 hours.
In addition, the invention also provides application of the dantrolene sodium crystal form A in preparing a medicine for treating malignant hyperpyrexia.
The preparation method provided by the invention has the advantages that the required solvent is a conventional solvent, the preparation cost is low, the preparation method is simple to operate, the reaction condition is mild, the control is easy, the reproducibility is good, and the target product crystal form can be stably obtained.
Compared with the prior art, the invention has the advantages that:
compared with other crystal forms of dantrolene sodium in the prior art, the crystal form A of dantrolene sodium provided by the invention has better stability; patent CN 102302461B discloses a method for preparing a lyophilized powder injection, wherein a raw material drug is converted into an amorphous form by lyophilization, and the process has the problems of water loss of the crystal form and different loading amount in the preparation process, so that the stability test data (moisture, content, etc.) of the lyophilized powder injection cannot be equal to the crystal form of the raw material drug. According to the invention, influence factor experiments under the conditions of high temperature, high humidity and illumination further prove that the dantrolene sodium crystal form A has better stability than the crystal form in the patent CN 102302461B. Meanwhile, the method for preparing the dantrolene sodium crystal form A is simple and convenient to operate and is more suitable for industrial production.
Drawings
Embodiments of the invention are described in detail below with reference to the attached drawing figures, wherein:
figure 1 is an X-ray powder diffraction pattern of crystalline form a of dantrolene sodium of example 2.
FIG. 2 is a differential scanning thermogram (DSC chart) of crystalline form A of dantrolene sodium of example 2.
FIG. 3 is a thermogravimetric analysis (TG plot) of crystalline form A of dantrolene sodium of example 2.
FIG. 4 is a high performance liquid chromatogram of the dantrolene sodium form A of example 2 and a control crystal after being placed under high temperature, high humidity and high light conditions for 10 days for stability comparison. FIG. 4(A) Placement conditions: the high temperature is 60 ℃; FIG. 4(B) Placement conditions: high humidity RH 92.5%; FIG. 4(C) Placement conditions: the illumination was 4500 lx.
Figure 5 is a graph comparing the dissolution profiles of crystalline form a of dantrolene sodium from example 2. FIG. 5(A) is a plan view; fig. 5(B) is a side view.
Detailed Description
The invention is illustrated below with reference to specific examples. It will be understood by those skilled in the art that these examples are for illustrative purposes only and are not intended to limit the scope of the present invention in any way.
The experimental procedures in the following examples are conventional unless otherwise specified. The raw materials and reagents used in the following examples are all commercially available products unless otherwise specified.
Example 1: preparation of crude dantrolene sodium
Mixing dantrolene (140g), methanol (2765g) and 30% sodium methoxide (161g), stirring and reacting for 1 hour at room temperature, slowly cooling to-5 +/-5 ℃, stirring for 3-4 hours, filtering, and vacuum drying for 24-48 hours at 40-60 ℃ to obtain a dantrolene sodium crude product.
Example 2: preparation of dantrolene sodium crystal form A
At 25 ℃, 1g of the dantrolene sodium crude product prepared in example 1 is added into a 25ml single-mouth bottle, 10ml of methanol is added, the temperature is controlled to be 20-30 ℃, the mixture is stirred for 16 hours, the pressure is reduced and filtered, and vacuum drying is carried out for 48 hours at 40 ℃ to obtain orange to dark orange crystalline solid which is the dantrolene sodium crystal form A.
An X-ray powder diffraction pattern of the dantrolene sodium crystal form A is measured by a Bruker D8 advanced diffractometer, and the measurement conditions are as follows: ka X-ray with copper target wavelength of 1.54nm, theta-2 theta goniometer, Mo monochromator, Lynxeye detector under 40kV and 40mA operation condition. The instrument was calibrated with silicon carbide prior to use. The acquisition software was a Diffracplus XRD Commander. The samples were tested at room temperature and placed on a non-reflective plate. The detection conditions are as follows: angle range: 3-40 ° 2 θ, step size: 0.02 ° 2 θ, speed: 0.2 sec/step. The X-ray powder diffraction values are characterized as follows in bragg 2 theta angle, interplanar spacing d and relative intensity I (expressed as a percentage relative to the most intense ray).
The characterization data are shown in table 1, and the X-ray powder diffraction pattern of the dantrolene sodium crystal form A, which can be clearly obtained from the table 1, has characteristic diffraction peaks corresponding to the corresponding positions of the 2 theta values.
TABLE 1 characterization data for X-ray powder diffraction pattern of crystalline form A of dantrolene sodium
A differential scanning thermogram (DSC) of the crystal form A of dantrolene sodium is shown in figure 2;
the thermogravimetric plot (TG) of dantrolene sodium form a is shown in figure 3.
Example 3: preparation of dantrolene sodium crystal form A
Adding 5g of dantrolene sodium crude product into a 250ml three-necked bottle at 25 ℃, sequentially adding 85ml of methanol and 15ml of purified water, controlling the temperature to be 20-30 ℃, stirring for 6 hours, filtering, and vacuum drying for 36 hours at 50 ℃ to obtain an orange to dark orange crystalline solid which is a dantrolene sodium crystal form A.
The analysis result of the dantrolene sodium crystal form a prepared in the detection example 3 has no obvious difference with the analysis result of the dantrolene sodium crystal form a prepared in the example 2, and the stable dantrolene sodium crystal form a can be repeatedly obtained.
Example 4: preparation of dantrolene sodium crystal form A
Adding 5g of dantrolene sodium crude product into a 250ml three-necked bottle at 25 ℃, sequentially adding 75ml of methanol and 25ml of purified water, controlling the temperature to be 20-30 ℃, stirring for 6 hours, filtering, and vacuum drying for 36 hours at 40 ℃ to obtain an orange to dark orange crystalline solid which is a dantrolene sodium crystal form A.
The analysis result of the dantrolene sodium crystal form a prepared in the detection example 4 has no obvious difference with the analysis result of the dantrolene sodium crystal form a prepared in the detection example 2, and the stable dantrolene sodium crystal form a can be repeatedly obtained.
Example 5: preparation of dantrolene sodium crystal form A
Adding 5g of dantrolene sodium crude product into a 250ml three-necked bottle at 25 ℃, sequentially adding 65ml of methanol and 35ml of purified water, controlling the temperature to be 20-30 ℃, stirring for 6 hours, filtering, and vacuum drying for 36 hours at 50 ℃ to obtain an orange to dark orange crystalline solid which is a dantrolene sodium crystal form A.
The analysis result of the dantrolene sodium crystal form a prepared in the detection example 5 has no obvious difference with the analysis result of the dantrolene sodium crystal form a prepared in the detection example 2, and the stable dantrolene sodium crystal form a can be repeatedly obtained.
Example 6: preparation of dantrolene sodium crystal form A
Adding 40g of a dantrolene sodium crude product into a 250ml three-necked bottle at 25 ℃, sequentially adding 400ml of methanol and 400ml of purified water, controlling the temperature to be 20-30 ℃, stirring for 6 hours, filtering, and vacuum drying for 36 hours at 50 ℃ to obtain an orange to dark orange crystalline solid which is a dantrolene sodium crystal form A.
The analysis result of the dantrolene sodium crystal form a prepared in the detection example 6 has no obvious difference with the analysis result of the dantrolene sodium crystal form a prepared in the detection example 2, and the stable dantrolene sodium crystal form a can be repeatedly obtained.
Example 7: dantrolene sodium crystal form A accelerated test
1. Preparation of dantrolene sodium crystalline form
Dantrolene sodium form a prepared as in example 2
2. The results of accelerated stability test of dantrolene sodium crystal form A under the conditions of 40 ℃ (RH 75% + -5%) constant temperature and humidity are detailed in Table 2
TABLE 2 dantrolene sodium accelerated test results
And (4) conclusion: the product is placed for 6 months under the accelerated test condition, and no obvious change is seen in each investigation item.
Example 8: stability test of dantrolene sodium crystal form A
1. Preparation of dantrolene sodium form group 1: crystalline form a of dantrolene sodium prepared in example 2
Group 2: patent CN 102302461B dantrolene sodium crystal form prepared in example 1
2. The crystal form of dantrolene sodium is subjected to an influence factor experiment under the conditions of high temperature, high humidity and illumination:
(1) the experimental steps are as follows: taking appropriate amount of dantrolene sodium, respectively placing in high temperature 60 deg.C, high humidity RH 92.5% and illumination 4500lx environment for 10 days, sampling, and inspecting related substances. The related substances are detected according to the general rule 0512 of high performance liquid chromatography of the four ministry of China pharmacopoeia 2015 edition, and a reference substance consists of impurities B (N-carbamoyl-N- [ [ [5- (4-nitrophenyl) -2-furyl ] methylene ] amino ] glycine), C (5-p-nitrophenyl furfural) and dantrolene, wherein the concentrations are respectively 1.0 mu g/ml, 0.5 mu g/ml and 0.5 mu g/ml, the concentration of a test substance is 500 mu g/ml, and the test substance is the sample to be detected of the group 1 and the group 2. (2) The experimental results are as follows: after being respectively placed under the conditions of high temperature, high humidity and strong light for 10 days, the content of the dantrolene sodium crystal form A impurities is obviously lower than that of the dantrolene sodium crystal form in the embodiment 1 of the patent CN 102302461B, namely, the dantrolene sodium prepared by the comparative patent method has poorer stability at 60 ℃ at high temperature, 92.5 percent at high humidity and 4500lx under illumination compared with the dantrolene sodium prepared by the application method.
Specifically, the method comprises the following steps: the dantrolene sodium crystal forms are respectively placed under the conditions of high temperature of 60 ℃, high humidity RH of 92.5% and illumination of 4500lx for 10 days to form impurity contrast. From the results, under the conditions of high temperature of 60 ℃, high humidity of RH of 92.5% or illumination of 4500lx, the impurity proportion of the crystal form a of the present application relative to the crystal form CN 102302461B of the patent is obviously reduced, the total impurity proportion is 1.6% for the comparison crystal form at high temperature of 60 ℃, 0.37% for the crystal form of the present invention, 0.28% for the comparison crystal form at high humidity of RH of 92.5%, 0.06% for the crystal form of the present invention, 0.53% for the comparison crystal form at illumination of 4500lx, and 0.15% for the crystal form of the present invention, and the specific results are shown in table 3.
As can be seen from fig. 4, when the crystal of the present invention and the control crystal were placed under the conditions of 60 ℃ at high temperature, 92.5% RH at high humidity and 4500lx illumination for 10 days for substance detection, the main characteristic peak (dantrolin sodium) appeared at the same time, but the control crystal also showed significantly more impurity peaks and larger relative response value in addition to the main characteristic peak, indicating that the control crystal showed more impurities under the above-mentioned environmental conditions. Wherein, the day 0 data refers to the detection result of the sample which is not subjected to influence factor investigation under normal conditions (normal temperature, drying and dark).
TABLE 3 stability test results for dantrolene sodium
Example 9: dissolution capacity experiment of dantrolene sodium crystal form A
1. Preparation of crystalline form of dantrolene sodium crystalline form a prepared in example 2
2. The dissolution rate of dantrolene sodium under heating conditions of 40 ℃, normal humidity and daily day light.
3. The experimental steps are as follows:
(1) 400mg of dantrolene sodium and 60g of mannitol are weighed.
(2) About 1100ml of purified water was taken and the pH was adjusted to 10.5-11.5 with NaOH solution.
(3) 540ml of the above sterilized water for injection was weighed into a beaker having a volume of 1L.
(4) Sterilizing purified water, maintaining at 35-50 deg.C, adding prepared mannitol, and stirring at rotation speed for about 5min to dissolve completely.
(5) Adding 400mg of dantrolene sodium, stirring by magnetic force, keeping the stirring speed in a beaker the same, and observing the dissolution condition of the raw materials.
4. The experimental results are as follows:
the result shows that under the conditions of heating condition of 40 ℃, conventional humidity and daily illumination in daytime, the dantrolene sodium crystal form A is completely dissolved 90 seconds after being put into the solution, and the solution is orange and clear. Therefore, the crystal form A in the application has excellent dissolving performance and has important significance for the preparation of pharmaceutical preparations. The results of the specific dissolution rates are detailed in Table 4 and the dissolution states are shown in FIG. 5.
TABLE 4 dantrolene sodium dissolution rate results
Solvent: purified water
The above description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the invention, and any modifications, equivalents, improvements and the like made within the spirit and principle of the present invention should be included in the scope of the present invention.
Claims (9)
1. A crystal form A of dantrolene sodium has a structure shown as a formula (I)
The crystal form A has characteristic absorption peaks at 8.3 +/-0.2 degrees, 11.0 +/-0.2 degrees, 12.4 +/-0.2 degrees, 16.6 +/-0.2 degrees and 27.3 +/-0.2 degrees by X-ray powder diffraction represented by 2 theta angles by using Cu-Ka radiation.
2. Form A of dantrolene sodium according to claim 1, characterized in that it has characteristic absorption peaks at 4.0 ± 0.2 °, 8.3 ± 0.2 °, 11.0 ± 0.2 °, 12.4 ± 0.2 °, 15.2 ± 0.2 °, 16.6 ± 0.2 °, 19.2 ± 0.2 °, 20.9 ± 0.2 °, 22.2 ± 0.2 °, 23.5 ± 0.2 °, 25.9 ± 0.2 °, 27.3 ± 0.2 ° with X-ray powder diffraction at 2 θ angles using Cu-Ka radiation.
3. The dantrolene sodium form a according to claim 2, wherein said form a is obtained by X-ray powder diffraction at 2 Θ angles using Cu-Ka radiation, and the peaks of said form a diffraction are shown in figure 1 of the specification.
4. The dantrolene sodium form a according to claim 3, wherein the differential scanning thermal analysis of form a is shown in figure 2 of the specification.
5. The dantrolene sodium form a of claim 4, wherein the thermogravimetric analysis of form a is as shown in figure 3 of the specification.
6. The preparation method of the dantrolene sodium crystal form A specifically comprises the following steps:
step 1) adding a dantrolene sodium crude product into a methanol solution, controlling the temperature to be 20-30 ℃, stirring, and filtering under reduced pressure;
and 2) drying the product obtained in the step 1) in vacuum to obtain the dantrolene sodium crystal form A.
7. The method for preparing dantrolene sodium crystal form a according to claim 6, wherein the concentration of methanol in step 1) is 50-100% (v/v), and the stirring time is 6-16 hours.
8. The process for preparing dantrolene sodium form a according to claim 6, wherein in step 2) the drying temperature is 40 to 50 ℃ and the drying time is 36 to 48 hours.
9. Use of dantrolene sodium form a according to any of claims 1 to 8, for the preparation of a medicament for the treatment of malignant hyperthermia.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN2019103137051 | 2019-04-18 | ||
CN201910313705 | 2019-04-18 |
Publications (1)
Publication Number | Publication Date |
---|---|
CN111825662A true CN111825662A (en) | 2020-10-27 |
Family
ID=72913642
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202010310215.9A Pending CN111825662A (en) | 2019-04-18 | 2020-04-17 | Dantrolene sodium crystal form and preparation method thereof |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN111825662A (en) |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20040242646A1 (en) * | 2001-06-23 | 2004-12-02 | Anderson David M. | Treatment using dantrolene |
CN101254176A (en) * | 2008-02-25 | 2008-09-03 | 北京阜康仁生物制药科技有限公司 | Freeze-dried powder needle preparations taking dantrolene sodium as activity component and preparation technique thereof |
CN102302461A (en) * | 2011-09-02 | 2012-01-04 | 海南锦瑞制药股份有限公司 | Dantrolene sodium freeze-dried powder injection for injection and preparation method thereof |
-
2020
- 2020-04-17 CN CN202010310215.9A patent/CN111825662A/en active Pending
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20040242646A1 (en) * | 2001-06-23 | 2004-12-02 | Anderson David M. | Treatment using dantrolene |
CN101254176A (en) * | 2008-02-25 | 2008-09-03 | 北京阜康仁生物制药科技有限公司 | Freeze-dried powder needle preparations taking dantrolene sodium as activity component and preparation technique thereof |
CN102302461A (en) * | 2011-09-02 | 2012-01-04 | 海南锦瑞制药股份有限公司 | Dantrolene sodium freeze-dried powder injection for injection and preparation method thereof |
Non-Patent Citations (3)
Title |
---|
NOZOMI HISADA ET AL.: "Characterizing the dissolution profiles of supersaturable salts, cocrystals, and solvates to enhance in vivo oral absorption", 《EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS》 * |
周月广 等: "丹曲林钠杂质B的合成", 《合成化学》 * |
曹志荣 等: "肌肉松弛剂丹曲林钠的合成", 《中国医药工业杂志》 * |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP2020002168A (en) | Crystalline forms of macrolide, and uses thereof | |
CN110494423A (en) | The happy novel crystal forms and preparation method thereof cut down for Buddhist nun's mesylate | |
CN114149476B (en) | Polymorphic substance of ribonucleoside analogue, preparation method and application thereof | |
CN102702008A (en) | Agomelatine sulfuric acid composition and preparation method thereof | |
CN105061420B (en) | A kind of crystal formation of JAK inhibitor and its preparation method and application | |
EP3569590A1 (en) | (r)-4-hydroxy-2-oxo-1-pyrrolidineacetamide crystal form, preparation method therefor, and application thereof | |
Gong et al. | Structure, characterization, solubility and stability of podophyllotoxin polymorphs | |
CN111825662A (en) | Dantrolene sodium crystal form and preparation method thereof | |
CN104379557B (en) | The preparation method of agomelatine crystal form I | |
CN113402458B (en) | Enrofloxacin eutectic and preparation method thereof | |
TWI770934B (en) | Crystal form of monomaleate of tyrosine kinase inhibitor and preparation method thereof | |
CN108570045B (en) | Crystal form of anisodamine hydrobromide, preparation method and pharmaceutical composition thereof | |
CN113354642A (en) | Huperzine B crystal and preparation and application thereof | |
CN110563644A (en) | Novel crystal form of Lunvatinib mesylate | |
CN103059013A (en) | New crystal of Dasatinib monohydrate and preparation method thereof | |
CN108727417B (en) | Polycyclic compound sodium salt, and polycrystalline type, preparation method and application thereof | |
CN114380833A (en) | Ketorolac and 4-pyridinecarboxamide eutectic crystal and preparation method thereof | |
Shiying et al. | Screening, Characterization and Evaluation of Mangiferin Polymorphs | |
Yang et al. | Screening, characterization and evaluation of mangiferin polymorphs | |
CN108358842A (en) | His quinoline not crystal form of moral and preparation method thereof, its pharmaceutical composition and purposes | |
CN114276358B (en) | Polymorphs of oxycodone hydrochloride, preparation method and application thereof | |
CN110177779A (en) | A kind of crystal form and its preparation method and application of virus protein inhibitor medicaments VX-787 | |
CN109053718B (en) | Rosiglitazone saccharin salt and preparation method thereof | |
CN118307610A (en) | Rhodiola rosea glycoside crystal form and preparation method thereof | |
CN100436411C (en) | Tiopronin amino salt, and its preparing method |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination |