KR20130003602A - Sustained release microparticle composition and methods for the production thereof - Google Patents
Sustained release microparticle composition and methods for the production thereof Download PDFInfo
- Publication number
- KR20130003602A KR20130003602A KR1020110065045A KR20110065045A KR20130003602A KR 20130003602 A KR20130003602 A KR 20130003602A KR 1020110065045 A KR1020110065045 A KR 1020110065045A KR 20110065045 A KR20110065045 A KR 20110065045A KR 20130003602 A KR20130003602 A KR 20130003602A
- Authority
- KR
- South Korea
- Prior art keywords
- release
- sustained
- tamsulosin
- enteric
- particulate composition
- Prior art date
Links
Images
Classifications
-
- 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
- A61K31/13—Amines
- A61K31/145—Amines having sulfur, e.g. thiurams (>N—C(S)—S—C(S)—N< and >N—C(S)—S—S—C(S)—N<), Sulfinylamines (—N=SO), Sulfonylamines (—N=SO2)
-
- 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
- A61K47/38—Cellulose; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1617—Organic compounds, e.g. phospholipids, fats
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1682—Processes
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Inorganic Chemistry (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Medicinal Preparation (AREA)
Abstract
Description
The present invention relates to the preparation of tamsulosin or a pharmaceutically acceptable salt thereof. The invention also relates to a process for the preparation of said formulation.
Tamsulosin is a prostate smooth muscle selective α1 blocker and is useful for urination disorders caused by benign prostatic hyperplasia, and the recommended daily dose is 0.2-0.8 mg. Tamsulosin, unlike other α1 blockers, such as doxazosin and terazosin, has a high selectivity for prostate smooth muscle and low action on blood vessels, which greatly reduces side effects such as orthostatic hypotension. However, since the drug is very strong, the dosage is very low, and the absorption in vivo is also very fast. In spite of the high selectivity for prostate smooth muscle, a sudden excessive rise in blood drug concentration causes side effects such as orthostatichypotension.
To overcome this problem, U.S. Patent No. 4,772,475 (Korean Patent No. 67,674) discloses a sustained release formulation containing tamsulosin. According to this prior art, tamsulosin and 50% by weight or more of a unit forming material selected from the group consisting of crystalline cellulose, chitin and chitosan are mixed, and the mixture is a water-insoluble polymer which is an acrylic acid polymer, an acrylic acid copolymer or a cellulose derivative. A method of preparing tamsulosin-containing sustained-release granules is disclosed by adding a release controlling agent selected from the group consisting of a solution or suspension of a substance and then granulating it.
However, in the case of the sustained-release granule preparation, at least 16.2% and at most 60.4% of the drug is released 1 hour after the start of dissolution in the first liquid (about pH 1.2), which is an acidic condition. In case of transferring to a liquid (about pH 6.8), more than 90% of the drug is released in 1 hour, so that the sustained release of the preparation is not sufficient (see Korean Patent Application No. 10-2003-0015391). .
Because of these problems, orthostatic hypotension, a major side effect of tamsulosin, occurs frequently within 4 hours after drug administration, and 8.4% (0.4 mg tamsulosin administration) and 18.1% (0.8 mg tamsulosin administration) among patients. Considering the fact that abnormal ejaculation occurs in patients with [Prescription Drug Reference (PDR), 2002], sustained-release preparations according to the prior art require more efficient control of drug release, In other words, it needs to be designed to be less affected by the environment. Specifically, it is important to reduce the side effects that can be caused by large amounts of tamsulosin being absorbed at one time by allowing the drug to be released at a constant rate (0th rate drug release).
A large number of tamsulosin-containing sustained-release preparations currently on the market mainly use enteric polymers to control drug release. Therefore, the drug release can be properly suppressed by the release control of the enteric polymer in the stomach when taking, but when the agent is passed to the small intestine over time, the solubility of the enteric polymer is rapidly increased, so a large amount of the drug is released at once. There is a problem that can be released. Many commercially available formulations simply use enteric polymers to coat the core material with enteric polymers and tamsulosin dissolved or dispersed coatings to control the release of tamsulosin. It has the problem of being released all at once.
In addition, most existing formulations are manufactured in place of tablets, which are the most commonly used formulations for pharmaceuticals, and coated with the granules, thereby preparing release control formulations containing tamsrosine, to facilitate release control. However, in order to coat these granules, a special coating device is required, and when manufactured using the coating method, there is a disadvantage that the release control layer may be broken when tableting.
Therefore, the present inventors, while studying the formulation of tamsulosin, can spray-dry the tamsulosin, ethyl cellulose and enteric polymer at a specific ratio together to produce a sustained release microparticles, do not use the coating technology in the preparation The present invention was completed by confirming that there is no possibility of damaging the release control layer during tableting, and at the same time, tablets of tamsulosin having sustained release and enteric release characteristics can be prepared.
The present invention is to provide a sustained release particulate composition comprising tamsulosin or a pharmaceutically acceptable salt thereof, ethylcellulose and an enteric polymer having sustained release, enteric release characteristics.
In addition, the present invention provides a simple and efficient method for producing a sustained-release particulate composition without the damage of the release control layer that can occur during tableting, by the spray-drying to prepare the sustained-release particulate composition by a separate coating process It is for.
In order to solve the above problems, the present invention provides a sustained-release particulate composition comprising tamsulosin or a pharmaceutically acceptable salt thereof, ethylcellulose and enteric polymer.
The term 'tamsulosin' used in the present invention has the chemical name of (R) -5- (2- (2- (2-ethoxyphenoxy) ethylamino) propyl) -2-methoxybenzenesulfonamide As a compound, it means a drug used for the prevention or treatment of enlarged prostate.
As used herein, the term "pharmaceutically acceptable salt" means a formulation of a compound that does not cause serious irritation to the organism to which the compound is administered and does not impair the biological activity and the properties of the compound. The pharmaceutical salts include acids that form non-toxic acid addition salts containing pharmaceutically acceptable anions, for example inorganic acids such as hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, hydrobromic acid, hydroiodic acid, and the like, tartaric acid, formic acid, Organic carbon acids such as citric acid, acetic acid, trichloroacetic acid, trichloroacetic acid, gluconic acid, benzoic acid, lactic acid, fumaric acid, maleic acid, salicylic acid, etc., such as methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, etc. Acid addition salts formed by sulfonic acid or the like. For example, pharmaceutically acceptable carboxylic acid salts include metal salts or alkaline earth metal salts formed by lithium, sodium, potassium, calcium, magnesium, amino acid salts such as lysine, arginine, guanidine, dicyclohexylamine, N Organic salts such as -methyl-D-glucamine, tris (hydroxymethyl) methylamine, diethanolamine, choline and triethylamine and the like. Tamsulosin according to the present invention may also be converted to its salts by conventional methods.
'Ethyl cellulose' used in the present invention is a kind of water-insoluble polymer and serves as a sustained-release membrane for controlling the release of tamsulosin, an effective drug. Other water soluble high molecular materials that can be used include hydroxypropyl cellulose, hydroxypropyl methyl cellulose, polyvinyl pyrrolidone, copolyvidone, polyvinyl alcohol and the like.
As used herein, the term enteric polymer refers to a polymer that is insoluble or stable under acidic conditions of less than pH 5, and that dissolves or decomposes under conditions of pH 5 or higher. Enteric polymers that can be used in the present invention include hydroxypropyl methylcellulose acetate succinate, hydroxypropylmethyl cellulose phthalate, hydroxymethyl cellulose phthalate, cellulose acetate phthalate, cellulose acetate succinate, cellulose acetate maleate, cellulose At least one enteric cellulose derivative selected from benzoate phthalate, cellulose propionate phthalate, methylcellulose phthalate, carboxymethyl ethyl cellulose or ethyl hydroxyethyl cellulose phthalate; Styrene, acrylic acid copolymer, acrylic acid acrylic acid, acrylic acid copolymer, acrylic acid methacrylic acid copolymer, acrylic acid butyl acid, styrene, acrylic acid copolymer, methacrylic acid, acrylic acid acrylic copolymer, methacrylic acid, acrylic acid ethyl copolymer or At least one enteric acrylic acid copolymer selected from methyl acrylate, methacrylic acid and oxyl acrylate copolymers; Vinyl acetate, maleic anhydride copolymer, ethylene, maleic anhydride copolymer, vinyl butyl ether, maleic anhydride copolymer, acrylonitrile, methyl acrylate, maleic anhydride copolymer or acrylic acid butyl, styrene, maleic anhydride copolymer One or more enteric maleic acid copolymers selected from among them; The polyvinyl alcohol phthalate, polyvinyl acetal phthalate, polyvinyl butylate phthalate or polyvinyl acetacetal phthalate may be selected from one or more selected from the group consisting of at least one enteric polyvinyl derivative.
Preferably, at least one selected from hydroxypropyl methyl cellulose phthalate, hydroxypropyl methyl cellulose acetate succinate, and methacrylic acid-ethyl acrylate copolymer can be used.
Ethyl cellulose and enteric polymers alone do not exhibit adequate drug release behavior, so it is preferable to use them together.
When the ethyl cellulose and the enteric polymer according to the present invention are used together, a sustained-release particulate composition having controlled release sustained release and enteric release characteristics may be prepared. That is, the sustained-release particulate composition of the present invention is preferably enteric sustained-release particulate.
As can be seen in FIGS. 3 and 4, the second liquid when ethyl cellulose and the enteric polymer are used at a constant ratio as compared with the case where only the enteric polymer is used (Comparative Example 4) and when only the ethyl cellulose is used (Comparative Example 5) It was confirmed that the emission pattern was observed with a gentle slope at. In other words, sustained sustained release and enteric release from the intestine were observed only when both ethylcellulose and enteric polymer were used. In the case of tamsulosin, in which drug release control is important due to severe side effects, sustained sustained release and enteric release characteristics result in a marked decrease in side effects and improvement in dosage.
In the present invention, the weight ratio of the ethyl cellulose and the enteric polymer is preferably 0.33: 1 to 0.66: 1. If less than 0.33: 1, there is a disadvantage that the initial release proceeds too fast, and if more than 0.66: 1, the release is excessively delayed.
The average particle diameter of the sustained-release fine particles according to the present invention is preferably about 0.1 µm to 100 µm, and more preferably about 5 µm to 100 µm, but is not particularly limited as long as it does not feel greasy in the oral cavity. If the average particle diameter of the sustained-release microparticles is smaller than 0.1 µm, it is difficult to impart sustained release in the current formulation technology.
In addition, the present invention comprises the steps of preparing a mixture comprising tamsulosin or a pharmaceutically acceptable salt thereof, ethylcellulose and enteric polymer (step 1); And dissolving the mixture in a solvent including ethanol and methylene chloride, followed by spray-drying to prepare a sustained release particulate composition (step 2).
Step 1 is a step of preparing a mixture comprising tamsulosin or a pharmaceutically acceptable salt thereof, ethylcellulose, and an enteric polymer, and preparing a mixture for spray drying. At this time, the mixture contains ethylcellulose and enteric polymer, so that the sustained-release microparticles can be formed together with tamsulosin or a pharmaceutically acceptable salt thereof when spray drying.
In step 1, the weight ratio of the ethyl cellulose and the enteric polymer is preferably 0.33: 1 to 0.66: 1. If less than 0.33: 1, there is a disadvantage that the initial release proceeds too fast, and if more than 0.66: 1, the release is excessively delayed.
The enteric polymer that can be used in step 1 is hydroxypropyl methylcellulose acetate succinate, hydroxypropylmethyl cellulose phthalate, hydroxymethyl cellulose phthalate, cellulose acetate phthalate, cellulose acetate succinate, cellulose acetate maleate, At least one enteric cellulose derivative selected from cellulose benzoate phthalate, cellulose propionate phthalate, methylcellulose phthalate, carboxymethyl ethyl cellulose, or ethylhydroxyethyl cellulose phthalate; Styrene, acrylic acid copolymer, acrylic acid acrylic acid, acrylic acid copolymer, acrylic acid methacrylic acid copolymer, acrylic acid butyl acid, styrene, acrylic acid copolymer, methacrylic acid, acrylic acid acrylic copolymer, methacrylic acid, acrylic acid ethyl copolymer or At least one enteric acrylic acid copolymer selected from methyl acrylate, methacrylic acid and oxyl acrylate copolymers; Vinyl acetate, maleic anhydride copolymer, ethylene, maleic anhydride copolymer, vinyl butyl ether, maleic anhydride copolymer, acrylonitrile, methyl acrylate, maleic anhydride copolymer or acrylic acid butyl, styrene, maleic anhydride copolymer One or more enteric maleic acid copolymers selected from among them; The polyvinyl alcohol phthalate, polyvinyl acetal phthalate, polyvinyl butylate phthalate or polyvinyl acetacetal phthalate may be selected from one or more selected from the group consisting of at least one enteric polyvinyl derivative.
Preferably, at least one selected from hydroxypropyl methyl cellulose phthalate, hydroxypropyl methyl cellulose acetate succinate, and methacrylic acid-ethyl acrylate copolymer can be used.
Step 2 is a step of dissolving the mixture prepared in step 1 in a solvent including ethanol and methylene chloride and then spray-drying, to prepare a sustained-release particulate composition through spray-drying.
As used herein, the term 'spray-drying' refers to a method of spraying a material into hot air and drying it with air flow in a fine droplet of 1 mm or less. Atomizing the material means that it receives the latent heat of evaporation required for drying by increasing the surface area per unit of material from the surrounding hot air, and is effective for evaporating the moisture of the material into the air flow at the water level.
The solvent used in step 2 is used to form a spray liquid for spray-drying the mixture.
The solvent for preparing the spray liquid is a substance which shows high solubility without changing the physical properties of these substances and is easily volatilized during the spray-drying process, using dichloromethane, chloroform, methanol, ethanol alone or a combination of two or more thereof. Can be used, preferably a mixture of ethanol and methylene chloride.
The average particle diameter of the sustained-release fine particles prepared in step 2 is characterized in that about 0.1㎛ to 100㎛. More preferably, the average particle diameter of the sustained-release particles prepared in step 2 is about 5 µm to 100 µm, but is not particularly limited as long as it does not feel slippery in the oral cavity. If the average particle diameter of the sustained-release microparticles is smaller than 0.1 µm, it is difficult to impart sustained release in the current formulation technology.
The present invention includes a pharmaceutical composition comprising the sustained-release particulate composition prepared by the above method. The sustained-release particulate composition can be added to the conventional additives to form a multi-unit formulation such as granules, oral tablets, tablets, capsules according to the conventional formulation method. The multi-unit preparations thus formed are separated into individual units upon in vivo administration and are widely dispersed in the gastrointestinal tract, thereby slowly releasing the active substance in the intestine, thereby obtaining sustained sustained release and enteric release characteristics.
Sustained release particulate composition comprising tamsulosin or a pharmaceutically acceptable salt thereof, ethylcellulose and enteric polymer according to the present invention has sustained release and enteric release characteristics and is applied as an oral tablet because the average particle diameter is small to 100 μm. Even if there is an effect that can minimize the foreign body.
In addition, the present invention is a method for producing the sustained-release particulate composition by spray-drying the preparation of the sustained-release particulate composition does not damage the release control layer that may occur during tableting, and because there is no separate coating process simple and efficient This has the effect of producing a sustained release fine particle composition.
1 is a graph showing the dissolution patterns with time in the first liquid of the tablets prepared in Comparative Examples 1 to 5,
2 is a graph showing the dissolution patterns of the tablets prepared in Comparative Examples 1 to 5 over time in the second liquid,
Figure 3 is a graph showing the dissolution patterns with time in the first liquid of the tablets prepared in Examples 1 to 3 and the tablets prepared in Comparative Examples 4 and 5,
Figure 4 is a graph showing the dissolution patterns with time in the second liquid of the tablets prepared in Examples 1 to 3 and the tablets prepared in Comparative Examples 4 and 5,
5 is a SEM photograph of the tablet prepared in Example 3.
Hereinafter, the present invention will be described in more detail with reference to Examples. These examples are intended to illustrate the present invention more specifically, but the scope of the present invention is not limited by these examples.
Example One
A mixture was prepared by mixing 10 parts by weight of ethanol and 15 parts by weight of methylene chloride with respect to a total of 60.00 mg of a composition having a composition of tamsulosin 0.200 mg, ethyl cellulose 44.475 mg, Eudragit L-100 14.825 mg, and aerosil 0.500 mg. . Thereafter, the mixture was spray dried using a spray dryer of Buchi (Swiss) mini spray dryer (B-290) model to prepare a sustained release particulate composition. At this time, inlet temperature: 50-80 ° C., aspirater speed: 80-100%, and pump speed: 5-50% were maintained under the manufacturing conditions.
60 parts by weight of the sustained-release particulate composition prepared above was mixed with 50 parts by weight of spray-dried mannitol, and a mixture was prepared using distilled water. The association was granulated using No. 35 sieve and dried at 60 ° C. using a dryer.
110 parts by weight of the dried granules were mixed with 80 parts by weight of spray-dried mannitol, 50 parts by weight of crospovidone, 5 parts by weight of magnesium styrate, and 5 parts by weight of aerosil, and then a tablet was manufactured using a tablet press.
Example 2
A sustained-release particulate composition was prepared in the same manner as in Example 1 except that a composition having a composition of tamsulosin 0.200 mg, ethyl cellulose 41.889 mg, Eudragit L-100 17.411 mg, and aerosil 0.500 mg was used. The tablets were then prepared by granulation and tableting.
Example 3
The sustained-release particulate composition was prepared in the same manner as in Example 1 except that the composition having a composition of tamsulosin 0.200 mg, ethyl cellulose 35.580 mg, Eudragit L-100 23.720 mg, and aerosil 0.500 mg was used. After the preparation, the tablets were prepared by granulation and tableting.
compare Example 1 to 5
Each of the five compositions having the composition of Table 1 was mixed with 10 parts by weight of ethanol and 15 parts by weight of methyleneene chloride to prepare a mixture. Thereafter, the mixture was spray dried using a spray dryer (B-290) model to prepare a particulate composition. At this time, inlet temperature: 50-80 ° C., aspirater speed: 80-100%, and pump speed: 5-50% were maintained under the manufacturing conditions.
60 parts by weight of the prepared particulate composition was mixed with 50 parts by weight of spray-dried mannitol, and a coalition was prepared using distilled water. The association was granulated using No. 35 sieve and dried at 60 ° C. using a dryer.
110 parts by weight of the dried granules were mixed with 80 parts by weight of spray-dried mannitol, 50 parts by weight of crospovidone, 5 parts by weight of magnesium styrate, and 5 parts by weight of aerosil, and then a tablet was manufactured using a tablet press.
(Unit: mg)
Experimental Example 1: dissolution test
The dissolution test was carried out on the tablets prepared in Examples 1 to 3 and Comparative Examples 1 to 5 using the paddle method of the Korean Pharmacopoeia (9th Amendment) using a Vision Elite 8 (Hanson, USA) eluator. . At this time, the eluate was 500 mL of the first solution (pH1.2) and 500 mL of the second solution (pH 6.8). The temperature was 37 ± 0.5 ° C., and the rotation speed of the paddle was 100 rpm. 5 ml samples were taken from the eluate, which was immediately filtered using a PDVF syringe filter and then checked for concentration using HPLC and fluorescence detector. Based on the concentration, the tablet dissolution patterns of Examples 1 to 3 and Comparative Examples 1 to 5 were analyzed and shown in FIGS. 1 to 4.
1 and 2 are graphs showing the dissolution patterns in the first liquid and the second liquid of Comparative Examples 1 to 5; According to FIGS. 1 and 2, in Comparative Example 4, a total of 20% of the first liquid and the second liquid were not released, and in Comparative Example 2, both the first liquid and the second liquid were released at a high rate. When administered, it was confirmed that all of the stomach rapidly disintegrated and released, causing side effects of tamsulosin such as orthostatic hypotension. In Comparative Examples 1, 3, and 5, it is suitable as an enteric preparation because it shows a release pattern in the second liquid, but at least 70% of the drug is released at a rapid rate and 15 to 45 minutes before 30 minutes have passed in the second liquid. The release was completed in minutes, confirming that it is not suitable as a sustained release preparation.
3 and 4 are graphs showing the dissolution patterns in the first liquid and the second liquid of Examples 1 to 3 and Comparative Examples 4 and 5. FIG. According to FIGS. 3 and 4, in the case of Examples 1 to 3, the release rate is suppressed very low so that the amount of drug released in the first liquid is almost low, and the second liquid is continuously released for 3 hours as a measurement time with a gentle slope. Sustained release was confirmed. In addition, it was confirmed that the release pattern can be effectively controlled according to the composition (weight ratio of enteric polymer and ethyl cellulose).
Experimental Example 2: Sue castle Particulate SEM observe
As a result of observing the sustained release fine particle composition prepared in Example 3 using Scanning Electron Microscopy, it was confirmed that the sustained release fine particles having an average particle diameter of 100 μm or less were produced.
Claims (8)
Dissolving the mixture in a solvent comprising ethanol and methylene chloride and then spray-drying to prepare a sustained release particulate composition.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR1020110065045A KR20130003602A (en) | 2011-06-30 | 2011-06-30 | Sustained release microparticle composition and methods for the production thereof |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR1020110065045A KR20130003602A (en) | 2011-06-30 | 2011-06-30 | Sustained release microparticle composition and methods for the production thereof |
Publications (1)
Publication Number | Publication Date |
---|---|
KR20130003602A true KR20130003602A (en) | 2013-01-09 |
Family
ID=47835775
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
KR1020110065045A KR20130003602A (en) | 2011-06-30 | 2011-06-30 | Sustained release microparticle composition and methods for the production thereof |
Country Status (1)
Country | Link |
---|---|
KR (1) | KR20130003602A (en) |
-
2011
- 2011-06-30 KR KR1020110065045A patent/KR20130003602A/en not_active Application Discontinuation
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP5285913B2 (en) | Solid release modified pharmaceutical dosage form for oral administration | |
CA2539982C (en) | Pantoprazole multiparticulate formulations | |
CN101977593B (en) | Drug delivery systems comprising weakly basic drugs and organic acids | |
US20060115525A1 (en) | Pharmaceutical compositions | |
JP2001172201A (en) | Use of film coating for masking the taste for oral administration, oral administration form and production thereof | |
JP6148252B2 (en) | New formulation | |
US20090042914A1 (en) | Delayed release formulations of 6-mercaptopurine | |
KR101122447B1 (en) | Novel preparation | |
JP2002526437A (en) | AGITATION-INDEPENDENT PHARMACEUTICAL MULTI-UNIT RELEASE FORMULATION AND PROCESS FOR PRODUCING THE SAME | |
KR20090122344A (en) | Controlled release preparation containing cilostazol and process for the preparation thereof | |
JP2006512358A (en) | Tamsulosin controlled release pharmaceutical composition | |
JP5685641B2 (en) | Oral pharmaceutical composition comprising fenofibric acid and alkalizing agent | |
WO2005009416A1 (en) | Modified release compositions for minocycline | |
AU2008365126A1 (en) | Tamsulosin pellets for fixed dose combination | |
US8821936B2 (en) | Solid pharmaceutical formulation | |
JP6147711B2 (en) | Pharmaceutical composition and method for producing the same, orally disintegrating tablet and method for producing the same | |
EP3796908B1 (en) | Controlled release propiverine formulations | |
CA2547586C (en) | Controlled-release pharmaceutical formulation | |
KR20130003602A (en) | Sustained release microparticle composition and methods for the production thereof | |
KR20030076634A (en) | Medicinal composition | |
WO2020048449A1 (en) | Solid pharmaceutical composition containing 1,3,5-triazine derivative or salt thereof | |
KR100396443B1 (en) | Solubilized Felodipine Containing Sustained Release Preparations and it's Manufacturing Process | |
AU2016374382A1 (en) | Pulsatile release pharmaceutical composition comprising naftazone or one of its salts | |
KR20020031421A (en) | Oral dosage forms |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
WITN | Withdrawal due to no request for examination |