KR20160146428A - Stable amorphous solifenacin pharmaceutical composition containing solifenacin or its pharmaceutically acceptable salt and lactose, and method of preparation thereof - Google Patents
Stable amorphous solifenacin pharmaceutical composition containing solifenacin or its pharmaceutically acceptable salt and lactose, and method of preparation thereof Download PDFInfo
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- KR20160146428A KR20160146428A KR1020150083722A KR20150083722A KR20160146428A KR 20160146428 A KR20160146428 A KR 20160146428A KR 1020150083722 A KR1020150083722 A KR 1020150083722A KR 20150083722 A KR20150083722 A KR 20150083722A KR 20160146428 A KR20160146428 A KR 20160146428A
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- solifenacin
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- GFASKLQGVGSFSB-YANBTOMASA-N O=C(N1[C@@H](c2ccccc2)c2ccccc2CC1)/[O]=C\C1C(CC2)CCN2C1 Chemical compound O=C(N1[C@@H](c2ccccc2)c2ccccc2CC1)/[O]=C\C1C(CC2)CCN2C1 GFASKLQGVGSFSB-YANBTOMASA-N 0.000 description 1
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/439—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom the ring forming part of a bridged ring system, e.g. quinuclidine
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/472—Non-condensed isoquinolines, e.g. papaverine
- A61K31/4725—Non-condensed isoquinolines, e.g. papaverine containing further heterocyclic rings
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
Abstract
Description
The present invention relates to a stable amorphous solifenacin pharmaceutical composition comprising lactis as a stabilizing agent in combination with solifenacin or a pharmaceutically acceptable salt thereof, a process for producing the same, and a method for producing a stable amorphous solifenacin pharmaceutical composition, And a pharmaceutical composition for preventing or treating diseases or gastrointestinal diseases.
International Application Publication No. WO96 / 20194, the call to Soli Pena of formula (1) New (solifenacin) the chemical name 1-azabicyclo [2.2.2] oct-3-yl (1 R) -1- phenyl-3,4 dihydro -1 H - isoquinolin-2-carboxylate as, neurogenic pollakiuria, neurogenic bladder, nocturnal enuresis, unstable bladder, bladder celebrate, urinary disorders such as urinary incontinence and frequent urination, etc. of chronic cystitis, chronic obstructive pulmonary disease, chronic bronchitis, , Respiratory diseases such as asthma and rhinitis, irritable bowel syndrome, convulsive colitis and diverticulitis.
A series of quinuclidine derivatives including solifenacin or its salts have excellent selective antagonism to the muscarinic M3 receptor and are useful for the treatment of neurogenic urinary frequency, neurogenic bladder, nocturnal encephalopathy, unstable bladder, And is useful as a preventive or therapeutic agent for respiratory diseases such as urinary or chronic obstructive pulmonary disease, chronic bronchitis, asthma and rhinitis
Example 8 of European Patent No. 801067 describes a process for preparing solifenacin hydrochloride, wherein crystals crystallized in a mixed solvent containing acetonitrile and diethyl ether have a melting point of 212 to 214 캜, a degree of non-linearity [?] 25D = 98.1 (c = 1.00, EtOH).
However, when formulating a succinic acid salt of solifenacin or an amorphous form of solifenacin or its salt by a general formulation method, the solifenacin succinic acid salt, which is a main drug in the prepared preparation, The above-mentioned European patent has not been disclosed, nor is it mentioned.
Meanwhile, in June 2003, the Japanese Ministry of Health, Labor and Welfare published the medical certificate No. 0624001, which describes the specification of the preparation, that is, the decomposition product (impurities) in the preparation, which is confirmed in the stability test . According to this, when the amount of the crude medicine to be administered on
Based on the results of current clinical trials, there are 2.5 mg tablets, 5 mg tablets and 10 mg tablets in the Solifenacin formulations scheduled to be marketed.
On the other hand, in order to prepare salts and crystal formulations having excellent pharmaceutical properties, it is necessary to satisfy physicochemical criteria such as (1) excellent solubility, (2) excellent stability, (3) non-hygroscopicity and (4) shall. Highly stable drugs have the advantage that they do not deteriorate even after storage for a long time. Drugs with high solubility can be expected to have a high effect because they exhibit a high blood concentration even at low doses because fast absorption occurs in stomach and intestines when taken orally . In general, the amorphous form of a drug has a high solubility, resulting in rapid absorption in the stomach and intestine, but has a disadvantage in that it is less stable than a crystalline form. Accordingly, there is a need for a stable, amorphous pharmaceutical composition comprising solifenacin or a salt thereof in order to improve the solubility and to ensure stability of the solifenacin or its salt.
[Patent Document 1] International Application No. WO96 / 20194
[Patent Document 2] European Patent No. 801067
[Non-Patent Document 1] Medical Center No. 0624001
It is an object of the present invention to provide a stable amorphous pharmaceutical composition comprising solifenacin or a pharmaceutically acceptable salt thereof.
It is another object of the present invention to provide a process for preparing the stable amorphous pharmaceutical composition.
It is still another object of the present invention to provide a pharmaceutical composition for preventing or treating urinary diseases, respiratory diseases or gastrointestinal diseases, which comprises the stable amorphous pharmaceutical composition as an active ingredient.
To this end, the present invention provides a stable amorphous soliphenacin pharmaceutical composition comprising solifenacin or a pharmaceutically acceptable salt thereof, and lactose as a stabilizer.
(1) dissolving solifenacin or a pharmaceutically acceptable salt thereof and lactose in water or a mixed solvent of water and an organic solvent, and (2) dissolving the solution produced in
The present invention also provides a pharmaceutical composition for preventing or treating urinary, respiratory or digestive diseases, which comprises the stable amorphous ssoliphenacin pharmaceutical composition as an active ingredient.
The stable amorphous solifenacin pharmaceutical composition comprising solifenacin or its pharmaceutically acceptable salt and lactose according to the present invention is excellent in heat stability and solubility and has good bioavailability, Can be usefully used as a preventive or therapeutic agent for respiratory diseases or gastrointestinal diseases.
1 shows the X-ray diffraction (XRD) diagram of the stable amorphous soliphenacin pharmaceutical composition prepared in Example 1. Fig.
FIG. 2 is an X-ray diffraction chart of the stable amorphous solid pharmaceutical composition prepared in Example 1 after storage at 60.degree. C. for 10 days. FIG.
The present invention provides stable amorphous soliphenacin pharmaceutical compositions comprising solifenacin or a pharmaceutically acceptable salt thereof and lactose as a stabilizer.
In the stable amorphous soliphenacin pharmaceutical composition of the present invention, lactose can increase the stability such as the thermal stability of solifenacin by forming an amorphous pharmaceutical composition together with solifenacin.
The lactose used in the present invention is a disaccharide to which galactose and glucose are bonded, which is also referred to as lactose or lactose, and has a structure of? -D-galactosyl- (1,4) -D-glucose. The molecular formula is C 12 H 22 O 11 , and there are two types, α and β types, depending on the form. Lactose is a component of mammalian milk, and is a safe stabilizer used primarily as a raw material for formulated milk powder for infant formula and as a medical nutrient.
The lactose used in the present invention may have a structure represented by the following formula (2).
As used herein, the term " pharmaceutically acceptable salt of solifenacin "means salts of solifenacin with inorganic acids such as hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid, nitric acid, phosphoric acid, or organic acids such as formic acid, acetic acid, propionic acid, oxalic acid, malonic acid, Acid addition salts with organic acids such as succinic acid, fumaric acid, maleic acid, lactic acid, malic acid, citric acid, tartaric acid, carbonic acid, picric acid, methanesulfonic acid, ethanesulfonic acid and glutamic acid and quaternary ammonium salts. Among them, a solifenacin succinate salt of the following formula (3) is preferable from the viewpoint of utility as a medicine.
The stable amorphous soliphenacin pharmaceutical compositions of the present invention exhibit amorphous character in X-ray powder diffraction analysis (XPRD). As a specific example thereof, the stable amorphous solid pharmaceutical composition prepared in Example 1 and the X-ray powder diffraction diagram after storage at 60 ° C for 10 days are shown in FIGS. 1 and 2, respectively.
The stable amorphous solid pharmaceutical composition according to the present invention has a water content of 1 to 10% by weight as measured by Karl-Fischer titrator (KF). Preferably, the moisture content of the stable amorphous soliphenacin pharmaceutical composition is about 2.6% by weight.
The stable amorphous solifenacin pharmaceutical composition according to the present invention maintains the amorphous state without melting while keeping the moisture content at about 2.6% even when it is left at 60 캜 for 10 days.
(1) dissolving solifenacin or a pharmaceutically acceptable salt thereof and lactose in water or a mixed solvent of water and an organic solvent, and (2) a step of dissolving 1, and lyophilizing the solution produced in step (1) to obtain a solid phase powder.
In one embodiment, the pharmaceutically acceptable salt of solifenacin that may be employed in the methods of manufacture of the present invention may be a solifenacin succinate salt.
In step (1) of the production method of the present invention, solifenacin or a pharmaceutically acceptable salt thereof and lactose are dissolved in water or a mixed solvent of water and an organic solvent. In this case, Can be determined. For example, dissolving solifenacin or a pharmaceutically acceptable salt thereof in water or a mixed solvent of water and an organic solvent, and then adding lactose to the resultant solution; Dissolving lactose in water or a mixed solvent of water and an organic solvent, and then adding solifenacin or a pharmacologically acceptable salt thereof to the resultant solution; Solifenacin or a pharmaceutically acceptable salt thereof and lactose may be simultaneously added to and dissolved in water or a mixed solvent of water and an organic solvent.
The lactose may be used in an amount of 1 to 4 equivalents, preferably 1 to 2 equivalents based on 1 equivalent of solifenacin or a pharmaceutically acceptable salt thereof.
The water or water-containing mixed solvent may be used in an amount of 1 to 100 times by volume, preferably 5 to 50 times by volume based on the volume of the solifenacin or a pharmaceutically acceptable salt thereof.
The mixed solvent of water and the organic solvent is a mixed solvent of water and an organic solvent selected from the group consisting of methanol, ethanol, acetone and acetonitrile. The mixing ratio of water to organic solvent may be 1: 100 to 100: 1 .
In step (2) of the production method of the present invention, freeze-drying can be carried out at -90 to -10 캜 for 1 to 10 days.
The stable amorphous soliphenacin pharmaceutical composition of the present invention can be obtained by recovering and drying the solid produced through lyophilization in
The pharmaceutical composition of the present invention may be formulated into any pharmaceutical preparation by appropriately adding various pharmaceutically acceptable additives. Any of these additives may be used as long as they are pharmaceutically acceptable as well as pharmacologically acceptable so long as they do not impair the purpose of the present invention. For example, a disintegrant, an acidifier, a foaming agent, an artificial sweetener, a flavoring agent, a lubricant, a colorant, a stabilizer, a buffer, an antioxidant, a surfactant and the like may be used. Examples of the disintegrating agent include corn starch, potato starch, calmelose calcium, sodium chloromelose, and low-substituted hydroxypropyl cellulose. Examples of the acidulant include citric acid, tartaric acid, malic acid and the like. As the foaming agent, for example, sodium bicarbonate and the like can be mentioned. Examples of the artificial sweetener include sodium saccharin, potassium glutilate, aspartame, stevia, and soymatin. Examples of the perfume include lemon, lemon lime, orange, menthol and the like. Examples of the lubricant include magnesium stearate, calcium stearate, sucrose fatty acid esters, talc, and stearic acid. Examples of the coloring agent include yellow ferric oxide, red ferric oxide, edible yellow No. 4 and No. 5, edible red No. 3, No. 102, and edible blue No. 3. Examples of the buffering agent include buffers such as citric acid, succinic acid, fumaric acid, tartaric acid, ascorbic acid or salts thereof, glutamic acid, glutamine, glycine, aspartic acid, alanine, arginine or salts thereof, magnesium oxide, zinc oxide, magnesium hydroxide, phosphoric acid, . Examples of the antioxidant include ascorbic acid, sodium nitrite, sodium sulfite, sodium hydrogen sulfite, sodium edetate, erythorbic acid, tocopheryl acetate, tocopherol, butylhydroxyanisole, dibutylhydroxytoluene, have. Examples of the surfactant include sodium lauryl sulfate, polyoxyethylene sorbitan aliphatic ester (polysorbate 80), polyoxyethylene hardened castor oil, and the like.
These additives may be suitably used singly or in combination of two or more.
The pharmaceutical preparations of the present invention may contain, as an active ingredient, an amorphous solifenacin pharmaceutical composition in an amount of 0.1 to 99% by weight, preferably 0.1 to 95% by weight, more preferably 1 to 70% by weight, based on the total weight of the preparation .
The pharmaceutical compositions according to the present invention may be administered to a patient in an effective amount via a variety of routes, for example, oral or parenteral routes. Preferably, the compositions of the present invention are prepared in an oral dosage form such as capsules, tablets, dispersions and suspensions. The capsules or tablets may be in enteric coated form or may contain pellets of enteric coated amorphous soliphenacin pharmaceutical compositions.
The dosage of the stable amorphous solipenacin pharmaceutical composition of the present invention is normally suitably selected according to the pharmaceutical use (indications), but is not particularly limited as long as it is a therapeutically effective amount or a prophylactically effective amount. A typical daily dose may be from 0.01 mg to 100 mg, preferably from 0.5 mg to 50 mg, more preferably from 0.5 mg to 10 mg, most preferably from 0.5 mg to 4 mg, based on the adult. The pharmaceutical composition of the present invention can be administered in the form of single dose or divided dose per day. However, the actual dosage of the active ingredient should be determined in light of various relevant factors, such as the route of administration, the age, sex and weight of the patient, and the severity of the disease, and accordingly, It does not.
[Example]
Hereinafter, the present invention will be described in more detail with reference to the following examples. However, the following examples are for illustrative purposes only and are not intended to limit the scope of the present invention.
Reference example : Used equipment And measurement conditions
The analytical values described in the following examples were measured as follows.
1) Chemical Purity (%): High Performance Liquid Chromatography (HPLC) (column: Develosil ODS-UG-5 column, internal diameter 4.6 mm x length 150 mm, detection wavelength: The solvent peak shown in the chromatogram was obtained by performing the elution with acetonitrile: pH 6.0 0.064 M potassium dihydrogenphosphate buffer = 50:50 (v / v), oven temperature: 40 ° C) And the chemical purity was calculated from the peak area of the amorphous solifenacin pharmaceutical composition.
At this time, potassium dihydrogenphosphate buffer was prepared by adjusting pH to 6.0 by adding 0.1 M phosphoric acid to 0.064 M potassium dihydrogenphosphate aqueous solution.
2) X-ray diffraction spectrum: Using a D8 Advance X-ray powder diffraction spectrometer (Bruker, Germany), Cu-K? Radiation (wavelength? = 1.54050 ANGSTROM).
3) The differential scanning calorimetry (DSC) was measured at a rate of + 1 ° C / min using a differential scanning calorimeter (STA S-1000, Scinco, Korea).
4) Nuclear Magnetic Resonance Spectrum (NMR): Measured using a 300 MHz FT-NMR spectrometer (Bruker, Germany).
5) Melting point: Measured using an automatic melting point apparatus (Buchi / Swiss, B-545).
6) Moisture Content: Measured by Karl-Fischer titrator (KF).
Example 1 Preparation of Amorphous Solifenacin Pharmaceutical Composition
20 g of the solifenacin succinate and 200 ml of water were mixed and dissolved at room temperature with stirring. To this solution was added 14.2 g of lactose and dissolved, followed by filtration through a membrane (0.45 um HV, available from Durapore). The filtrate was poured into a complicated flask, rapidly cooled and frozen, and lyophilized for 3 days at -80 ° C in a lyophilizer. The resulting solid was collected to obtain 32.3 g (yield: 94.5%) of amorphous soliphenazine composition as a solid phase powder.
The analytical values of the solid phase powder thus prepared are as follows:
Purity: 99.96% (measured by HPLC)
1 H-NMR (D 2 O , 300MHz) δ 6.8 ~ 7.2 (m, 10H), 6.06 (d, 1H), 4.61 (d, 1H), 4.39 (d, 1H), 3.45 ~ 3.90 (m, 15H) 1H), 1.73 (m, 2H), 1.73 (m, 2H), 3.10-3.24 (m, 5H)
Moisture content: about 2.6%
The XRD spectrum of the solid phase powder thus prepared is shown in Fig.
As shown in FIG. 1, the solid phase powder exhibited an amorphous characteristic peak.
Example 2: Preparation of amorphous soliphenacin pharmaceutical composition
10 g of the solifenacin succinate and 50 ml of water were mixed and dissolved at room temperature with stirring. To this solution, 7.1 g of lactose was added and dissolved, followed by membrane filtration. The filtrate was poured into a complicated flask, rapidly cooled and frozen, and then freeze-dried at -80 ° C for 3 days in a freeze dryer. The resulting solid was collected to obtain 15.7 g (yield: 91.8%) of amorphous soliphenacin composition as a solid phase powder.
The analytical values of the solid phase powder thus prepared are as follows:
Purity: 99.91% (measured by HPLC)
≪ 1 > H-NMR and moisture content The results were the same as in Example 1.
≪ Example 3 > Preparation of Amorphous Solifenacin Pharmaceutical Composition
10 g of the solifenacin succinate and 200 ml of water were mixed and dissolved at room temperature with stirring. To this solution, 7.1 g of lactose was added and dissolved, followed by membrane filtration. The filtrate was poured into a complicated flask, rapidly cooled and frozen, and then freeze-dried at -80 ° C for 3 days in a freeze dryer. The resulting solid was collected to obtain 15.8 g (yield: 92.8%) of amorphous soliphenacin composition as a solid phase powder.
The analytical values of the solid phase powder thus prepared are as follows:
Purity: 99.94% (measured by HPLC)
≪ 1 > H-NMR and moisture content The results were the same as in Example 1.
Example 4 Preparation of Amorphous Solifenacin Pharmaceutical Composition
20 g of the solid phenazine succinate and 800 ml of water were mixed and then dissolved at room temperature. To this solution was added 14.2 g of lactose and dissolved, followed by membrane filtration. The filtrate was poured into a complicated flask, rapidly cooled and frozen, and then freeze-dried at -80 ° C for 4 days in a freeze dryer. The resulting solid was collected to obtain 31.4 g (yield: 91.2%) of amorphous soliphenacin composition as a solid phase powder.
The analytical values of the solid phase powder thus prepared are as follows:
Purity: 99.93% (measured by HPLC)
≪ 1 > H-NMR and moisture content The results were the same as in Example 1.
Example 5: Preparation of amorphous soliphenacin pharmaceutical composition
10 g of the solifenacin succinate and 100 ml of water were mixed and dissolved at room temperature with stirring. To this solution was added 14.2 g (2.0 eq.) Of lactose and dissolved, followed by membrane filtration. The filtrate was poured into a complicated flask, rapidly cooled and frozen, and then freeze-dried at -80 ° C for 3 days in a freeze dryer. The resulting solid was collected to obtain 21.4 g (yield: 88.6%) of amorphous soliphenacin composition as a solid phase powder.
The analytical values of the solid phase powder thus prepared are as follows:
Purity: 99.93% (measured by HPLC)
< Example 6> amorphous Solifenacin Preparation of pharmaceutical compositions
10 g of the solifenacin succinate and 100 ml of water were mixed and dissolved at room temperature with stirring. To this solution was added 21.3 g (3.0 eq.) Of lactose and dissolved, followed by membrane filtration. The filtrate was poured into a complicated flask, rapidly cooled and frozen, and then freeze-dried at -80 ° C for 4 days in a freeze dryer. The resulting solid was collected to obtain 23.5 g (yield: 75.2%) of amorphous soliphenacin composition as a solid phase powder.
The analytical values of the solid phase powder thus prepared are as follows:
Purity: 99.92% (measured by HPLC)
< Example 7> amorphous Solifenacin Preparation of pharmaceutical compositions
10 g of the solifenacin succinate and 100 ml of water were mixed and dissolved at room temperature with stirring. To this solution was added 28.4 g (4.0 eq.) Of lactose and dissolved, followed by membrane filtration. The filtrate was poured into a complicated flask, rapidly cooled and frozen, and then freeze-dried at -80 ° C for 3 days in a freeze dryer. The resulting solid was collected to obtain 30.1 g (yield: 78.4%) of amorphous soliphenacin composition as a solid phase powder.
The analytical values of the solid phase powder thus prepared are as follows:
Purity: 99.91% (measured by HPLC)
≪ Comparative Example 1 > Preparation of amorphous solifenacin
20 g of the solifenacin succinate and 200 ml of water were mixed and stirred at room temperature to dissolve, followed by filtration through a membrane. The filtrate was poured into a complicated flask, followed by rapid cooling, followed by freeze-drying at -80 ° C for 2 days in a freeze dryer to obtain a solid. Thus, 19.7 g (yield: 98.4%) of amorphous solifenacin was obtained as a solid.
Purity: 99.94% by HPLC
Endothermic peak of DSC: 145 ° C
Moisture content: 1.5%
XRD: amorphous
< Comparative Example 2> Solifenacin Succinate and Lattoz's Preparation of mixtures
20 g of the solifenacin succinate and 14.2 g of lactose were added and mixed to prepare a mixture.
Purity: 99.88% (measured by HPLC)
Melting point: 155-160 DEG C
Moisture Content: 2.4%
< Test Example > Thermal stability test
To compare the thermal stability of the materials prepared in Example 1 and Comparative Examples 1 and 2, the materials were placed in a stability chamber and stored at 60 DEG C for 10 days, and then the resulting RRT (relative retention time) Were measured. The results are shown in Tables 1 to 3 below.
As can be seen from the results of Tables 1 to 3, the amorphous solifenacin pharmaceutical composition of Example 1 containing lactose exhibited, in terms of purity and impurity content, Phenanthine and the mixture of the solifenacin succinate salt and lactose of Comparative Example 2, respectively.
In particular, the amorphous solifenacin of Comparative Example 1 and the mixture of solifenacin succinate salt and lactose of Comparative Example 2 were all dissolved within one day at 60 ° C to show no crystallinity, and the lactose of Example 1 It was confirmed that the pharmaceutical composition containing amorphous solifenacin succinate maintains a stable and amorphous state while maintaining a moisture content of about 2.6% even at 60 ° C. for 10 days or longer.
Accordingly, the pharmaceutical composition of amorphous soliphene succinic acid salt containing lactose according to the present invention has improved stability compared to the conventional amorphous solifenacin or a mixture of solifenacin succinate and lactose, and also has a higher purity May be provided to the patient.
Claims (12)
[Chemical Formula 1]
Wherein the pharmaceutically acceptable salt of solifenacin is a solifenacin succinate salt of formula (3): < EMI ID =
(3)
Wherein said stable amorphous ssolifenacin pharmaceutical composition exhibits amorphousness in X-ray powder diffraction spectrum (XRPD) using Cu-K? Radiation.
(2) lyophilizing the solution produced in step 1 to obtain a solid phase powder.
Wherein the pharmaceutically acceptable salt of the solipenacin is a solifenacin succinate salt of the following formula 3:
(3)
Wherein in step (1), water or a mixed solvent of water and an organic solvent is used in an amount of 1 to 100 parts by volume based on the volume of the solifenacin or a pharmaceutically acceptable salt thereof.
Wherein the organic solvent in step (1) is selected from the group consisting of methanol, ethanol, acetone and acetonitrile.
Wherein the mixing ratio of water to organic solvent in the mixed solvent is 1: 100 to 100: 1 as a volume ratio.
Characterized in that in step (1), the lactose is used in an amount of 1 to 4 equivalents based on 1 equivalent of the soliphenacin or a pharmaceutically acceptable salt thereof.
Characterized in that lyophilization of step (2) is carried out at -90 to -10 < 0 > C for 1 to 10 days.
Wherein the urinary disease is selected from the group consisting of neurogenic urinary frequency, neurogenic bladder, enuresis, unstable bladder, bladder contraction, urinary incontinence in chronic cystitis and urinary frequency, and the respiratory disease is selected from the group consisting of chronic obstructive pulmonary disease, chronic bronchitis, asthma and rhinitis Wherein the gastrointestinal disease is selected from the group consisting of hypersensitivity bowel syndrome, convulsive colitis, and diverticulitis.
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| KR1020150083722A KR20160146428A (en) | 2015-06-12 | 2015-06-12 | Stable amorphous solifenacin pharmaceutical composition containing solifenacin or its pharmaceutically acceptable salt and lactose, and method of preparation thereof |
| JP2016115617A JP2017002044A (en) | 2015-06-12 | 2016-06-09 | Stable amorphous powders containing solifenacin or pharmaceutically acceptable salt thereof and lactose, and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20210114271A (en) | 2020-03-10 | 2021-09-23 | 주식회사 종근당 | Pharmaceutical composition comprising solifenacin or its pharmaceutically acceptable salts |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1996020194A1 (en) | 1994-12-28 | 1996-07-04 | Yamanouchi Pharmaceutical Co., Ltd. | Novel quinuclidine derivatives and medicinal composition thereof |
| EP2801067A1 (en) | 2012-01-03 | 2014-11-12 | Time Warner Cable, Inc. | Excluding specific application traffic from customer consumption data |
-
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- 2015-06-12 KR KR1020150083722A patent/KR20160146428A/en unknown
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1996020194A1 (en) | 1994-12-28 | 1996-07-04 | Yamanouchi Pharmaceutical Co., Ltd. | Novel quinuclidine derivatives and medicinal composition thereof |
| EP2801067A1 (en) | 2012-01-03 | 2014-11-12 | Time Warner Cable, Inc. | Excluding specific application traffic from customer consumption data |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20210114271A (en) | 2020-03-10 | 2021-09-23 | 주식회사 종근당 | Pharmaceutical composition comprising solifenacin or its pharmaceutically acceptable salts |
| KR20230065222A (en) | 2020-03-10 | 2023-05-11 | 주식회사 종근당 | Pharmaceutical composition comprising solifenacin or its pharmaceutically acceptable salts |
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