WO1994011031A1 - Procede de production d'un compose d'encapsulation - Google Patents

Procede de production d'un compose d'encapsulation Download PDF

Info

Publication number
WO1994011031A1
WO1994011031A1 PCT/JP1993/001614 JP9301614W WO9411031A1 WO 1994011031 A1 WO1994011031 A1 WO 1994011031A1 JP 9301614 W JP9301614 W JP 9301614W WO 9411031 A1 WO9411031 A1 WO 9411031A1
Authority
WO
WIPO (PCT)
Prior art keywords
cyclodextrin
extruder
solubility
clathrate
inclusion compound
Prior art date
Application number
PCT/JP1993/001614
Other languages
English (en)
Japanese (ja)
Inventor
Kouichi Nakamichi
Shougo Izumi
Hiroshi Fukui
Original Assignee
Nippon Shinyaku Co., Ltd.
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 Nippon Shinyaku Co., Ltd. filed Critical Nippon Shinyaku Co., Ltd.
Priority to AU53769/94A priority Critical patent/AU5376994A/en
Publication of WO1994011031A1 publication Critical patent/WO1994011031A1/fr

Links

Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B82—NANOTECHNOLOGY
    • B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y5/00—Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
    • 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
    • A61K47/50—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/69—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
    • A61K47/6949—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes
    • A61K47/6951—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes using cyclodextrin

Definitions

  • the present invention relates to a method for producing a cyclodextrin clathrate.
  • the extruder is a screw-type kneading extruder that is widely used in the processing of foods (cereals, proteins, livestock, fish, etc.) mainly in the food field.
  • clathrates Conventional methods for producing cyclodextrin clathrates (hereinafter simply referred to as “clathrates”) include the so-called saturated solution method (eg.
  • each of the above conventional methods has a disadvantage that it takes a long time to produce an inclusion compound.
  • time is mainly required for the precipitation of the clathrate
  • time is mainly required for removing water and organic solvents. This is because in the kneading method and the mixing and pulverizing method, kneading and the like must be sufficiently performed to obtain a homogeneous clathrate compound.
  • the kneading method and the mixing and pulverizing method do not require a large-scale apparatus as compared with the saturated solution method or the like, but it is difficult to perform kneading or mixing and pulverizing uniformly, and it is possible to obtain a high-quality inclusion compound with less unevenness. Have difficulty.
  • An object of the present invention is to provide a method for producing a high-quality inclusion compound in a large amount at a time simply and quickly.
  • the present inventors have found that the above object can be achieved by using an extruder that can continuously process a sample.
  • the present invention has been completed.
  • the gist of the present invention resides in that a multiaxial extruder is used in producing an inclusion compound.
  • the main part of the extruder is composed of a barrel called a barrel, a die corresponding to an exit, and a screw ( there is usually a plurality of barrels, through which the screw passes.
  • a barrel there is usually a plurality of barrels, through which the screw passes.
  • trapezoidal screw trapezoidal cut screw
  • trapezoidal river There are types such as a scuttle, ball screw, and knee paddle, and the combination can be arbitrarily performed.
  • the sample sent to the extruder moves in the barrel by a screw, and is subjected to processing such as shearing and mixing by the screw in the barrel, and is extruded as an object from the pores of the die.
  • each barrel and die have independent temperature control.
  • the extruder includes a single-screw extruder consisting of one screw and a multi-axle extruder consisting of two or more screws.
  • a multi-axis extruder In the multiaxial type, since multiple screws interfere with each other, the sample drug does not co-rotate with the screws, and physically generates high energy due to the entanglement of the multiple screws. It can be.
  • the above object can be sufficiently achieved by using a two-shaft extruder among multi-shaft types.
  • an extruder mainly used in the food field can be used as it is (JP-A-3-262461, JP-A-4-63567, etc.).
  • a mixed powder of cyclodextrin and a sample drug is put into a multi-axial extruder (hereinafter simply referred to as “extruder”) set at a predetermined temperature and processed.
  • extruder multi-axial extruder
  • the method for producing the clathrate compound can be exemplified by the above.
  • Methods for mixing cyclodextrin and sample drug before processing with an extruder include machines such as kneader mixers, V-type mixers, double cone mixers, cubic mixers, and ribbon mixers. By There are some ways to do this.
  • the powder which can be obtained by the raw material feeder equipped in the extruder to be used, at a constant speed
  • the powder which can be obtained by the raw material feeder equipped in the extruder to be used, at a constant speed
  • Examples of such an apparatus include a screw feeder, a table feeder, a belt conveyer-type quantitative feeder, and an electromagnetic feeder.
  • the cyclodextrin and the sample drug differ depending on the type of cyclodextrin, the type of sample drug, the type and model of the extruder to be used, etc .; It is possible to mix at a ratio of 1:10 (sample drug: cyclodextrin (molar ratio)), preferably 1: 1 to 1 ⁇ 4 (sample drug: cyclodextrin (molar ratio)). it can. Even outside this range, an inclusion compound may be produced by the method of the present invention, and such a case is also included in the present invention.
  • the amount of cyclodextrin is less than 0.5 for sample drug 1, the amount of sample drug that is not included in cyclodextrin increases, and the amount of cyclodextrin for sample drug 1 is more than 10 The amount of cyclodextrin not included is increased, neither of which is preferred.
  • the internal temperature inside the barrel can be set within a range that does not decompose the sample drug and cyclodextrin. There is no particular limitation. Specifically, it can be set within the range of 5 ° C to 300 ° C. Usually 15-120'C is sufficient. It is not always necessary to set the temperature of each barrel and die to the same value.
  • the screw rotation speed depends on the extruder used. Can be set within the allowable range. In general, an extruder with a longer barrel length can increase the rotation speed.
  • the shape and combination of the screws to be used can be selected without any particular limitation. It is preferable to use one or more paddles in the form of a kneading paddle having strong kneading action and shearing action.
  • the shape of the pores of the discharge die is not particularly limited, such as a circle, an ellipse, a square, and a hexagon. When the pores are circular, the diameter can be appropriately set. For example, 0.5 to 5 IM ⁇ can be mentioned.
  • cyclodextrin examples include ⁇ -cyclodextrin, / S-cyclodextrin, 7-cyclodextrin, and derivatives of these cyclodextrins (for example, Methylated cyclodextrins (eg, dimethyl-cyclodextrin, dimethyl- ⁇ -cyclodextrin, dimethyl-arcyclodextrin, trimethyl-cyclodextrin, trimethyl-
  • Hydroxyalkylated cyclodextrins for example, hydroxyshethyl-a-cyclodextrin, hydroxyshethyl / S-cyclodextrin, hydroxyshethyl-cyclodextrin, hydroxypropyl- ⁇ -cyclodextrin
  • Trin hydroxypropyl
  • Branched cyclodextrin eg For example, Darco Silou o: — Cyclodextrin, glucosisolate; 8 — Cyclodextrin, glucosyl 7 — Cyclodextrin, maltosyl-cyclodextrin, maltosyl yS — Cyclodextrin, maltosyl — Acyclodextrin, etc., ethylated cyclodextrin (eg, Jethyl- ⁇ -cyclodextrin, Dethyl-S / cyclodextrin, Jethyl-cyclodextrin, triethyl-cyclodextrin, triethyl-cyclodextrin) 7-cyclodextrin, carboxymethylethyl- ⁇ -cyclodextrin, carboxymethylethyl; 3-cyclodextrin, carboxymethylethyl- ⁇ -cyclodextr
  • the drug used in the present invention is not particularly limited as long as it is a drug that can be included in cyclodextrin.
  • indomethacin, ketoprofen, ibuprofen, virprofen Non-steroidal anti-inflammatory agents such as fusolefenanic acid, fenilbutazone, arobrinol, bifurnylacetic acid, antirheumatic agents, progesterone, testosterone, dexamethasone, betamethasone, predniblon, hydrocotylisone , Cortisone, triamcinolone, fluocinolone, steroids such as beclomethasone, medroxyprogesterone acetic acid, coughing agents such as codeine and arimemazine, diazepam, nitrazepam, te Derivatives of phenothiazines such as mazepam, oxazepam, triimibramin, chlorpromazine, psychotropic drugs such
  • Antiepileptic drugs such as vasodilators, antihypertensives, Hypoglycemic agents such as torptamide, cerebral function improvers such as nicergoline, essential oil components such as benzaldehyde, cahialdehyde, P-anisaldehyde, 1-menthol, d-hintflu, etc. Can be.
  • the extruder can be treated in a wet or suspended state by adding an appropriate amount of water or an appropriate amount of an organic solvent to a mixture of cyclodextrin and a sample drug in advance.
  • the extruder process can be performed while continuously supplying an appropriate amount of water or an appropriate amount of an organic solvent from a supply hole (connected to the inside of the cylinder) generally provided in the extruder.
  • a supply hole connected to the inside of the cylinder
  • the supply of water or an organic solvent can reduce the load on the screw rotating shaft, thereby facilitating the extruder treatment, and the supply of water can provide a high-quality clathrate.
  • the water or organic solvent varies depending on the type of cyclodextrin, the type of sample drug, the type of water or organic solvent to be added, the processing speed, the type and type of extruder, but the mixed powder (cyclodextrin) 5 to 300% (V / W), preferably 10 to 200% (V / W), based on the total amount of the drug and the sample drug.
  • the organic solvent examples include methanol, ethanol, getyl ether, methylene chloride, benzene, n-hexane, acetone, cyclohexane, chloroform, acetonitrile, and the like.
  • water not only water but also isotonic water such as physiological saline, neutral or acidic or basic buffer, ammonia water, or the like can be used.
  • the sample treated by the extruder becomes an inclusion compound and is continuously extruded from the pores of the die in a solid, solid melt or liquid state.
  • the shape of the clathrate it is possible to directly obtain an inclusion compound in a form that is easy to mold into a final dosage form. It can also be dried or pulverized as needed to form granules, capsules, tablets and the like.
  • Whether the product produced by the method of the present invention is an clathrate compound can be confirmed by nuclear magnetic resonance (NMR) spectrum, infrared (IR) absorption spectrum, differential scanning calorimetry (DSC), In addition to instrumental analysis such as powder X-ray diffraction, measurement of solubility and dissolution rate showing the special effects of clathrate compounds, Bioavailability tests and photostability tests can also be used.
  • NMR nuclear magnetic resonance
  • IR infrared
  • DSC differential scanning calorimetry
  • an inclusion compound of any shape can be obtained. Therefore, it is possible to produce a clathrate compound of small diameter columnar shape and flake shape, which is difficult by the conventional method.
  • an inclusion compound can be produced at a relatively low temperature, and thus the method of the present invention is particularly effective when a drug that is easily decomposed by heat is used as an inclusion compound.
  • the extruder Since the extruder has a self-cleaning mechanism, the inside of the barrel of the extruder is less susceptible to dirt, and cleaning is easier than the conventional method. Therefore, the use of a chlorine-based cleaning solvent or the like is not required, or even if used, only a small amount is required, and problems such as wastewater treatment can be reduced.
  • the method of the present invention is an advantageous method for industrial use.
  • Example 1 A mixture of 150 g of indomethacin and 560 g of ⁇ -six dextrin (hereafter referred to as “/ 3-CyD”) has a first barrel temperature of 25 and a second, third, fourth, and fifth barrel temperature of 60 eC. 40 g / mi in the barrel of a 2-axis extruder (Kurimoto Iron Works, KEXN-30S-20, the same applies hereinafter) set at a temperature of 60, a die (5 caliber, 1 hole), a temperature of 60, and an extrusion speed of 80 rpni.
  • the molding process is performed by continuously supplying water at a supply speed of 10 ml / min while simultaneously supplying water at a supply speed of 10 ml / min through the supply holes provided in the extruder. An inclusion compound was obtained.
  • Example 2 Treatment was performed in the same manner as in Example 1 except that the water supply rate was set to 20 ral / min to obtain an inclusion compound.
  • the treatment was performed in the same manner as in Example 1 except that the water supply rate was 30 ml / min, to obtain an inclusion compound.
  • a supply speed of 45 g / min into the barrel of a twin-screw extruder set at 80 rpm simultaneously supplying water at a rate of 10 ml / min through the supply holes provided in the extruder
  • the molding process was carried out by continuously supplying the compound, and an inclusion compound was obtained.
  • the treatment was carried out in the same manner as in Example 4 except that the water supply rate was 30 ml / min, to obtain an inclusion compound.
  • compound AJ N- [2- (2 (1H-tetrazol-5-yl) phenylthio) -phenyl] -4-1-hexoxybenzamide (hereinafter referred to as “compound AJ”) 80 and ⁇ -cyclodextrin emissions (hereinafter " ⁇ - that C y Dj) a powder mixture of 165g at the first barrel temperature 25, second barrel temperature 70 e C, at a third barrels temperature 90, Te fourth barrel temperature 100, the fifth barrel At a temperature of 100, a die (flat type, 5 strikes x 40 thighs), a temperature of 80 ° C, and a continuous feed rate of 70 g / min into the barrel of a twin-screw extruder set at an extrusion speed of 150 rpm, at the same time
  • the molding process was performed by continuously supplying water at a supply rate of 70 ml / min from the supply hole provided in the extruder, and an inclusion compound was obtained.
  • a mixed powder of 80 g of compound A and 195 g of / S—CyD was treated in the same manner as in Example 7 to obtain an inclusion compound.
  • a mixture of 100 g of felinetoin and 450 g of ⁇ -CyD was mixed at a first temperature of 25 barrels, a second, third, fourth and fifth barrel temperature of 40 and a die (caliber 1 ⁇ , 5 hole) temperature 35 ' C, Extrusion speed While continuously feeding at a supply speed of 10 g / min into the barrel of a twin-screw extruder set at lOOrpm, water is simultaneously discharged from the supply hole provided in the extruder at 10ml / min. min supply The molding process was performed by continuously supplying at a constant speed to obtain an inclusion compound.
  • a mixed powder of 20 g of benzaldehyde and 215 g of 9 CyD was treated in the same manner as in Example 10 to obtain an inclusion compound.
  • a mixed powder of 20 g of benzaldehyde and 245 g of arcyclodextrin (hereinafter referred to as “ ⁇ -CyD”) was treated in the same manner as in Example 10 to obtain an inclusion compound.
  • a mixed powder of 50 g of diphdinapine and 165 g of / S-CyD was put into a mill (Ishikawa-type stirring crusher, model 16) together with 215 ml of water and kneaded. Then, 10 minutes, 30 minutes and 1 hour after starting the mill, remove the kneading solution, dry the mixture in a dryer at 60 ° C, and stop the mill after 3 hours. Then, the whole container was dried in the same manner, and the kneaded material on the bottom and side surfaces of the container was used as a sample for solubility measurement.
  • Test example 1 Prototypes of the clathrate obtained in Example 1 were crushed in a mortar, and those obtained by dissolving powdered Indian powder in sodium borate buffer 0.1M (pH 9.3, D20). down one NMR spectrum (unit: Varian Inc. XL- 2000 type, internal standard: Te Toramechirushira down, 12 e C) was measured. Confirmation of inclusion by 1-NMR
  • Example 1 As shown in Table 1, the 'H-NMR of the inclusion compound indomethacin obtained in Example 1 was shifted to a lower magnetic field side than that of the original powdered indomesin. This confirmed that the cyclodextrin clathrate was formed by the method of the present invention.
  • the clathrate compounds obtained in Examples 1, 2 and 3 were dried and crushed using a mortar, and then their solubility was measured. As a comparison, the solubility was also measured for powdered powder of India and the powder mixture (physical mixture) of India and 3-CyD used in Examples 1, 2 and 3. The solubility was determined by placing a fixed amount of each sample in a stoppered test tube, adding purified water, shaking at 25 ° C for 24 hours, filtering through a 0.45 £ in filter, and filtering the filtrate. It was measured by measuring the absorbance at 320 nm. Table 2 Solubility of insulin
  • a dissolution test was also performed on bulk indomethacin powder and a powder mixture of indomethacin and 1CyD used in Example 1.
  • the dissolution test was performed by weighing out 20 mg of indomethacin from each sample, putting it into 900 ml of purified water, and performing the paddle method (paddle rotation speed 100 rpm, measurement wavelength 320 mn, 37 ° C).
  • the paddle method paddle rotation speed 100 rpm, measurement wavelength 320 mn, 37 ° C.
  • the clathrate obtained in Example 1 showed a quicker elution property than bulk powder of indomestic acid or a physical mixture. Therefore, it was confirmed that the cyclodextrin inclusion compound of indomethacin was sufficiently formed by the method of the present invention.
  • Test example 4 The clathrates obtained in Examples 4, 5, 6 and Comparative Example 1 were dried and crushed using a mortar, and then their solubility was measured. The solubility was also measured for the raw powder of difedipin and the powder mixture (physical mixture) of difundipine and / 3-CyD used in Examples 4, 5, and 6 and Comparative Example 1. The solubility was measured in the same manner as in Test Example 2 by measuring the absorbance at 237 mn.
  • Dissolution test weighed two full et adipic 9 mg equivalent weight from each sample, which was put into purified water 900 meters l, paddle method (paddle rotation speed 100 rpm, measurement wavelength 237 nm, 37 e C) by a row ivy.
  • the clathrate compounds obtained in Examples 4, 5, and 6 showed a quicker elution property than the raw powder of edipin or the physical mixture. Therefore, it was confirmed that the cyclodextrin inclusion compound of diphedipine was sufficiently formed by the method of the present invention.
  • the clathrate obtained in Example 4 was dried for 40 minutes at an intake air temperature of 50 using a fluidized bed granulation dryer, and crushed using a fuser mill to obtain a 30 mesh (500 11 to 83 Mesh (180 111) range and the mixed powder of diphdipine and / 3-CyD used in Example 4 were filled into hard gelatin capsules (size 2) and weighed 1 weight. 0 to: 1 1 kg of male beagles are orally administered to 20 mg diphdipine per animal, and the concentration of difedipin in plasma is measured by high-performance liquid mouth chromatography.
  • Example 9 After the inclusion compound obtained in Example 9 was dried and pulverized using a mortar, its solubility was measured. For comparison, the solubility was also measured for the raw powder of fine powder and the mixed powder (physical mixture) used in Example 9. The solubility was measured in the same manner as in Test Example 2, except that the absorbance at 230 nm was measured after appropriately diluting with a phosphate buffer of pH II before measuring the absorbance. Table 6 Solubility of phenytoin
  • Example 9 As shown in Table 6, the solubility of the clathrate obtained in Example 9 was larger than that of the bulk powder, and it was confirmed that the clathrate of phenytoin was sufficiently formed.
  • FIG. 1 shows the results of the dissolution test.
  • the horizontal axis represents the time (minutes), and the vertical axis represents the elution rate (%.)---The elution curve of the inclusion compound obtained in Example 1--Hataichi is indomethacin 20rag and ⁇ -C y * 75 mg shows the elution curve of a physical mixture simply mixed with 75 mg, and 1 * 1 shows the elution curve of the bulk powder of indomethacin Figure 2 shows the results of the elution test The horizontal axis shows the time (minutes) The vertical axis represents the dissolution rate ⁇ %).
  • elution curves are as follows: -Hin-ichi represents the elution curve of a physical mixture obtained by simply mixing 9 fudipine 9rag and 3 -CyD 30 mg, and 1 *-represents the elution curve of the raw powder of 2Fudipine.
  • FIG. 3 shows the time course of plasma concentration of diflupine in beagle dogs.
  • the horizontal axis represents time (hours), and the vertical axis represents the plasma concentration (ng / ml) of difendipine.
  • - ⁇ - indicates the concentration of difludipine in plasma when the clathrate compound obtained in Example 4 was orally administered, and 1 *-indicates the oral administration of a physical mixture obtained by simply mixing 9 mg of diphdipine and 30 tng of -CyD. The values represent the concentration of diphdipine in the plasma in each case.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Nanotechnology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Health & Medical Sciences (AREA)
  • Biophysics (AREA)
  • Medical Informatics (AREA)
  • Molecular Biology (AREA)
  • General Engineering & Computer Science (AREA)
  • Crystallography & Structural Chemistry (AREA)
  • Biotechnology (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Polysaccharides And Polysaccharide Derivatives (AREA)
  • Medicinal Preparation (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

Procédé de production simple, rapide et en grandes quantités à la fois d'un composé d'encapsulation de haute qualité. Le procédé consiste à utiliser une extrudeuse à plusieurs vis, en particulier à deux vis.
PCT/JP1993/001614 1992-11-10 1993-11-08 Procede de production d'un compose d'encapsulation WO1994011031A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU53769/94A AU5376994A (en) 1992-11-10 1993-11-08 Enclosure compound manufacturing method

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP32610292 1992-11-10
JP4/326102 1992-11-10

Publications (1)

Publication Number Publication Date
WO1994011031A1 true WO1994011031A1 (fr) 1994-05-26

Family

ID=18184123

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP1993/001614 WO1994011031A1 (fr) 1992-11-10 1993-11-08 Procede de production d'un compose d'encapsulation

Country Status (2)

Country Link
AU (1) AU5376994A (fr)
WO (1) WO1994011031A1 (fr)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997018839A1 (fr) * 1995-11-23 1997-05-29 Janssen Pharmaceutica N.V. Melanges solides de cyclodextrines prepares par fusion-extrusion
DE19828881A1 (de) * 1998-06-22 1999-12-23 Schering Ag Oxidationsinhibitor bei Prostan-Derivaten
EA001456B1 (ru) * 1995-11-23 2001-04-23 Жансен Фармасетика Н.В. Твердые смеси циклодекстринов, полученные путем экструзии в расплаве

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH03290158A (ja) * 1990-04-06 1991-12-19 Meiji Milk Prod Co Ltd 食物繊維含有澱粉加工食品及びその製造法

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH03290158A (ja) * 1990-04-06 1991-12-19 Meiji Milk Prod Co Ltd 食物繊維含有澱粉加工食品及びその製造法

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997018839A1 (fr) * 1995-11-23 1997-05-29 Janssen Pharmaceutica N.V. Melanges solides de cyclodextrines prepares par fusion-extrusion
AU725204B2 (en) * 1995-11-23 2000-10-05 Janssen Pharmaceutica N.V. Solid mixtures of cyclodextrins prepared via melt-extrusion
EA001456B1 (ru) * 1995-11-23 2001-04-23 Жансен Фармасетика Н.В. Твердые смеси циклодекстринов, полученные путем экструзии в расплаве
DE19828881A1 (de) * 1998-06-22 1999-12-23 Schering Ag Oxidationsinhibitor bei Prostan-Derivaten

Also Published As

Publication number Publication date
AU5376994A (en) 1994-06-08

Similar Documents

Publication Publication Date Title
Mendonsa et al. Manufacturing strategies to develop amorphous solid dispersions: An overview
Patil et al. Hot-melt extrusion: from theory to application in pharmaceutical formulation
Bandari et al. Continuous twin screw granulation–An advanced alternative granulation technology for use in the pharmaceutical industry
Shah et al. Melt extrusion with poorly soluble drugs
Dumpa et al. Chronotherapeutic drug delivery of ketoprofen and ibuprofen for improved treatment of early morning stiffness in arthritis using hot-melt extrusion technology
JP5977331B2 (ja) 高い嵩密度と良好な流動性を有するセルロース誘導体の製造方法
ZA200209283B (en) Continuous production of pharmaceutical granulation.
Singhal et al. Hot melt extrusion technique
SK67298A3 (en) Solid mixtures of cyclodextrins prepared via melt-extrusion
KR102089112B1 (ko) 가열 용융 압출 담체용 히프로멜로오스 아세트산 에스테르 숙신산 에스테르, 가열 용융 압출용 조성물 및 가열 용융 압출 성형물의 제조 방법
WO1998035666A1 (fr) Preparation de pastilles de naproxene nanoparticulaire
PL208133B1 (pl) Kompozycja farmaceutyczna w postaci granulek oraz ciągły sposób wytwarzania kompozycji farmaceutycznej w postaci granulek
Shah et al. Melt extrusion in drug delivery: three decades of progress
Repka et al. Hot-melt extrusion technology
BR112014020718B1 (pt) composição polimérica extrusada sob fusão, processo para produzir uma composição polimérica extrusada sob fusão e uso de pelo menos um éter de celulose
Xue et al. A combined utilization of Plasdone-S630 and HPMCAS-HF in ziprasidone hydrochloride solid dispersion by hot-melt extrusion to enhance the oral bioavailability and no food effect
JP6751491B1 (ja) セルロース粉末、その使用および錠剤
WO2003077827A1 (fr) Procede de production de medicament solide en dispersion
CN100506234C (zh) 用于治疗溃疡性结肠炎和克罗恩病的含有5-氨基水杨酸的药物组合物的制备方法
de Assis et al. Hot-melt extrudability of amorphous solid dispersions of flubendazole-copovidone: An exploratory study of the effect of drug loading and the balance of adjuvants on extrudability and dissolution
Rajadhyax et al. Hot melt extrusion in engineering of drug cocrystals: a review
WO1994011031A1 (fr) Procede de production d'un compose d'encapsulation
WO2020072008A1 (fr) Nouvelles dispersions solides de sélinexor
JP2616253B2 (ja) 包接化合物の製法
Crowley et al. Hot melt extrusion of amorphous solid dispersions

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AU BR CA FI HU JP KR NO NZ RU US

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): AT BE CH DE DK ES FR GB GR IE IT LU MC NL PT SE

DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
121 Ep: the epo has been informed by wipo that ep was designated in this application
122 Ep: pct application non-entry in european phase
NENP Non-entry into the national phase

Ref country code: CA