WO2000064414A2 - Solid pharmaceutical formulations of acid-sensitive proton-pump blockers - Google Patents
Solid pharmaceutical formulations of acid-sensitive proton-pump blockers Download PDFInfo
- Publication number
- WO2000064414A2 WO2000064414A2 PCT/EP2000/003232 EP0003232W WO0064414A2 WO 2000064414 A2 WO2000064414 A2 WO 2000064414A2 EP 0003232 W EP0003232 W EP 0003232W WO 0064414 A2 WO0064414 A2 WO 0064414A2
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- acid
- active substance
- omeprazole
- preparation
- matrix
- Prior art date
Links
Classifications
-
- 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
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4184—1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
-
- 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
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
-
- 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
- A61K9/1623—Sugars or sugar alcohols, e.g. lactose; Derivatives thereof; Homeopathic globules
-
- 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
- A61K9/1635—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
-
- 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
- A61K9/1658—Proteins, e.g. albumin, gelatin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Definitions
- the present invention relates to solid preparations of an acid-labile proton pump blocker as an active substance, in which the active substance is X-ray amorphous in the form of a solid solution.
- the invention further relates to a method for producing such preparations.
- Acid-labile proton pump blockers in the sense of this invention are, in particular, acid-labile benzimidazoles such as, for example, pantoprazole, lansoprazole, pariprazole, lemnoprazole and in particular omeprazole.
- Omeprazole belongs to the so-called proton pump blocker substance class. It directly and dose-dependently inhibits the enzyme H + / K + -ATPase ("proton pump"), which is responsible for the secretion of gastric acid in the parietal cell of the stomach.
- proton pump H + / K + -ATPase
- Omeprazole has proven itself in the treatment of duodenal ulcer, ventricular ulcer, reflux oesophagitis and Zollinger-Ellision syndrome. Parenteral and solid oral drugs are used.
- Omeprazole is absorbed in the upper duodenum, the maximum plasma concentrations being reached 1 to 3 hours after application.
- Omeprazole decomposes very quickly to ineffective compounds under acidic conditions and under thermal stress. This process is associated with a brown-violet coloration of the white omeprazole powder. To prevent the undesired acid-related degradation reactions, oral omeprazole formulations must be completely protected against gastric juice so that the active ingredient can penetrate undamaged to the absorption site in the duodenum.
- DE-A 1204363 describes a pharmaceutical form consisting of three different layers.
- the first layer is soluble in the stomach, but insoluble in the intestine.
- the second layer is water-soluble (regardless of pH) and the third (outer) protective layer is an enteric coating.
- a disadvantage of such a form is that it is only slowly dissolved in the intestine and therefore the active ingredient is also released only slowly becomes. In the case of omeprazole, however, a quick release formulation is needed.
- EP-A 240904 describes pharmaceutical forms in which the active ingredient is embedded in a molecularly disperse form in a polymer matrix with the aid of melt extrusion. Such dosage forms are able to release the WS very quickly.
- a disadvantage of this form, however, is that temperature loads occur during production, which lead to degradation in the case of omeprazole.
- EP-0 496 437 describes pellet cores or tablets which contain omeprazole or an alkali salt of omeprazole together with an alkaline compound and are coated with a layer of water-soluble, film-forming auxiliaries, which preferably react alkaline, and are coated with an enteric end film.
- EP-A 0 239 200 describes the use of basic magnesium salts and / or basic calcium salts for stabilizing benzimidazole derivatives.
- the acid-labile proton pump inhibitor is embedded in a molecular dispersion in a matrix consisting of one or more polymers.
- Suitable polymers are: gelatin such as bovine gelatin, pork gelatin or fish gelatin, starch, dextrin, pectin, gum arabic, lignin sulfonates, chitosan, polystyrene sulfonate, alginates, casein, caseinate, methyl cellulose, carboxymethyl cellulose, hydroxypropyl cellulose, milk powder or dextran milk, whole milk Mixtures of these protective colloids.
- Homo- and copolymers based on the following monomers are also suitable: ethylene oxide, propylene oxide, maleic anhydride, lactic acid, glycolic acid, oc- and ⁇ -aspartic acid, N-vinylpyrrolidone, vinyl acetate, in particular polyvinylpyrrolidone with K values according to Fikentscher from 12 to 100 and copolymers of N-vinylpyrrolidone and vinyl acetate such as VP / VAc-60/40.
- gelatin types mentioned is particularly preferably used, in particular acidic or basic degraded gelatin with Bloom numbers in the range from 0 to 250, very particularly preferably gelatin A 100, A 200, B 100 and B 200 as well as low molecular weight, enzymatically degraded gelatin types the Bloom number 0 and molecular weights from 15000 to 25000 D such as Collagel A and Gelitasol P (from Stoess, Eberbach) and mixtures of these types of gelatin.
- Gastric juice-resistant polymers based on the Eudragit ® type are also suitable.
- the preparations also contain low molecular weight surface-active compounds.
- amphiphilic compounds or mixtures of such compounds are particularly suitable. Basically, all surfactants with an HLB value of 5 to 20 can be used.
- suitable surface-active substances are: esters of long-chain fatty acids with ascorbic acid, mono- and diglycerides of fatty acids and their oxyethylation products, esters of monofatty acid glycerides with acetic acid, citric acid, lactic acid or diacetyl tartaric acid, polyglycerol fatty acid esters such as e.g.
- the amounts of the various components are chosen according to the invention so that the preparations 1 to 90% by weight, preferably 5 to 60% by weight, of active substance, 1 to 95% by weight, preferably 10 to 90% by weight , one or more polymers and 0 to 50 wt .-%, preferably 0 to 20 wt .-%, of one or more low molecular weight stabilizers.
- the percentages by weight relate to a dry powder.
- the preparations may also contain antioxidants and / or preservatives to protect the active ingredient.
- Suitable antioxidants or preservatives are, for example, ⁇ -tocopherol, t-butyl hydroxytoluene, t-butyl hydroxy anisole, lecithin, ethoxyquin, methyl paraben, propyl paraben, sorbic acid, sodium benzoate or ascorbyl palmitate.
- the antioxidants or preservatives can be present in amounts of 0 to 10% by weight, based on the total amount of the preparation.
- the preparations may also contain plasticizers to increase the stability of the end product.
- plasticizers are, for example, sugar and sugar alcohols such as sucrose, glucose, lactose, invert sugar, sorbitol, mannitol, xylitol or glycerol. Lactose is preferably used as the plasticizer.
- the plasticizers can be contained in amounts of 0 to 50% by weight.
- auxiliaries such as binders, disintegrants, flavors, vitamins, colorings, wetting agents, additives influencing the pH value 20 (cf. H. Sucker et al., Pharmaceutical Technology, Thieme-Verlag, Stuttgart 1978) can also be obtained via the organic solvent or the aqueous phase are introduced.
- a solution of the active substance, the polymer and, if appropriate, the further substances mentioned above is first prepared in a suitable solvent.
- the total solids content of the solution is between 0.5 and 40% by weight, particularly preferably between 1 and
- Suitable solvents are water, organic solvents and homogeneous mixtures of these components. Alcohols, esters, ketones 35 and acetals are preferably used for the organic solvents. In particular, methanol, ethanol, n-propanol, isopropanol or acetone are used.
- the pH is adjusted to a value> 7 before the active ingredient is dissolved
- the pH is adjusted with the aid of substances which have a pKa value of> 7.
- Metal hydroxides, metal carbonates, metal phosphates, metal acetates are preferably used.
- the pH is preferably adjusted with ammonia water.
- the ammonium content of the finished dry powder is below the detection limit of ammonia (detection limit 0.1% by weight).
- the solution thus prepared is transferred to a dry powder. This is e.g. possible with the help of a spraying process.
- the temperature at the spray head is between 70 and 130 ° C, preferably between 80 and 110 ° C.
- the solution can also be converted into a dry powder using freeze drying or in a fluidized bed.
- the solid omeprazole preparations according to the invention enable a faster release of active substance compared to a formulation in which the omeprazole is in crystalline form.
- the solid preparations according to the invention show good chemical stability. This also applies to preparations that do not contain any detectable basic substances. Such good stability was not to be expected according to the prior art.
- the solid preparations according to the invention can be produced from a liquid solution using a spray process. Temperatures occur in this process which normally lead to a degradation of the active substance. Surprisingly, such an active ingredient degradation does not occur here.
- the dry powders obtained according to the invention can be filled into enteric-resistant, small intestine-soluble hard gelatin capsules or, in conventional formulations, pressed into tablets.
- preparations according to the invention can also be used for combination pharmaceutical forms, for example in combination with nonsteroidal anti-inflammatory analgesics, antibiotics such as erythromycin or clarithromycin, or with motility improvers.
- nonsteroidal anti-inflammatory analgesics antibiotics such as erythromycin or clarithromycin
- motility improvers motility improvers
- FIG 1 the scatter curves of omeprazole (curve a) and dry powder (curve b) are shown according to la.
- the omeprazole starting material is crystalline, as evidenced by the X-ray diagram, which is distinguished by a series of sharp interferences.
- the scatter curve of the dry powder shows only diffuse, broad interference maxima, which are typical for an amorphous material.
- the active ingredient is therefore present in the dry powder produced according to la, X-ray amorphous. This also applies to the otherwise crystalline auxiliaries lactose and ascorbyl palmitate.
- FIG. 2 shows the high-resolution 13C solid-state NMR spectra of omeprazole (curve a) and of the dry powder (curve b) according to FIG.
- the pure active ingredient omeprazole shows sharp signals, as is typical for crystalline substances.
- the 13C NMR spectrum of the dry powder shows strongly broadened active signals, as is typical for an amorphous material with a large number of realized conformations and random packings of the molecules.
- Tlrho (H) measurements with 13C detection were carried out.
- the exchange of spin energy between 1H cores (“spin diffusion”) is used to say something about the spatial proximity of the individual components on a length scale of approx. 1 nm.
- FIG. 3 shows the Tlrho (H) behavior of omeprazole (curve a) and the matrix (curve b) from preparation example la.
- the signal for the omeprazole comes from a signal of 126.4 ppm, which is typical for the omeprazole and is not covered by a signal from the matrix (cf. FIG. 2).
- the signal for the matrix originates from a signal of 172.7 ppm, which is typical for the matrix and is not covered by a signal of the omeprazole (cf. FIG. 2). It is easy to see that both lines are parallel. This course indicates the presence of a molecular mixture of active ingredient and matrix.
- FIG. 3 shows the Tlrho (H) behavior of omeprazole (curve c) and the matrix (curve d) of a physical mixture of crystalline omeprazole and the same auxiliaries and the same composition as from preparation example la.
- the signal for the omeprazole comes from a signal of 125.3 ppm which is typical of the omeprazole and is not covered by a signal from the matrix (cf. FIG. 2).
- the signal for the matrix originates from a signal of 175.7 ppm which is typical of the matrix and is not covered by a signal of the omeprazole (cf. FIG. 2). It can be clearly seen that in this case the straight lines have a different gradient. This course shows that the active ingredient and matrix are not in the form of a molecular mixture.
- the scatter curves of omeprazole (curve a) and of the dry powder (curve c) according to FIG. 2a are shown in FIG.
- the omeprazole starting material is crystalline, as evidenced by the X-ray diagram, which is distinguished by a series of sharp interferences.
- the scatter curve of the dry powder shows only diffuse, broad interference maxima, which are typical for an amorphous material.
- the active substance is therefore present in the dry powder produced according to 2a in an X-ray amorphous manner. This also applies to the otherwise crystalline auxiliary ascorbyl palmitate.
- An amorphous dry powder with an omeprazole content (determined by chromatography) of 30.7% by weight was obtained by spray drying.
- the Aran ⁇ nium content in the sample was 140 ppm.
- the scatter curves of omeprazole (curve a) and of the dry powder (curve d) according to FIG. 3a are shown in FIG.
- the omeprazole starting material is crystalline, as evidenced by the X-ray diagram, which is distinguished by a series of sharp interferences.
- the scatter curve of the dry powder shows only diffuse, broad interference maxima, as are typical for an amorphous material.
- the active substance is therefore present in the dry powder produced according to 3a in an X-ray amorphous manner.
- the ammonium content in the sample was 120 ppm.
- the scatter curves of omeprazole (curve a) and of the dry powder (curve e) according to FIG. 4a are shown in FIG.
- the omeprazole starting material is crystalline, as evidenced by the X-ray diagram, which is distinguished by a series of sharp interferences.
- the scatter curve of the omeprazole starting material is crystalline, as evidenced by the X-ray diagram, which is distinguished by a series of sharp interferences.
- Dry powder only diffuse, broad interference maxima, as are typical for an amorphous material.
- the active substance is therefore present in the dry powder produced according to 4a, X-ray amorphous. This also applies to the otherwise crystalline auxiliary substances lactose and ascorbyl palmitate.
- 70 mg spray embedding with omeprazole was carried out with 70 mg D-mannitol in a capsule size. 1 filled.
- the hard gelatin capsules filled in this way were coated gastro-resistant:
- Air volume controller position 6 - 7 pump (Watson Marlow): position 5 - 9
Abstract
Description
Claims
Priority Applications (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP00925201A EP1173152A2 (en) | 1999-04-23 | 2000-04-11 | Solid pharmaceutical formulations of acid-sensitive proton-pump blockers |
BR0012735-3A BR0012735A (en) | 1999-04-23 | 2000-04-11 | Solid preparation and process for producing preparations |
JP2000613405A JP2002542275A (en) | 1999-04-23 | 2000-04-11 | Solid pharmaceutical formulations of acid-labile proton pump inhibitors. |
CA002369951A CA2369951A1 (en) | 1999-04-23 | 2000-04-11 | Solid pharmaceutical formulations of acid-sensitive proton-pump blockers |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE19918434A DE19918434A1 (en) | 1999-04-23 | 1999-04-23 | Storage-stable solid proton pump inhibitor formulation useful e.g. for treating duodenal ulcers, comprises amorphous active agent embedded in auxiliary matrix |
DE19918434.8 | 1999-04-23 |
Publications (2)
Publication Number | Publication Date |
---|---|
WO2000064414A2 true WO2000064414A2 (en) | 2000-11-02 |
WO2000064414A3 WO2000064414A3 (en) | 2001-05-31 |
Family
ID=7905597
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/EP2000/003232 WO2000064414A2 (en) | 1999-04-23 | 2000-04-11 | Solid pharmaceutical formulations of acid-sensitive proton-pump blockers |
Country Status (6)
Country | Link |
---|---|
EP (1) | EP1173152A2 (en) |
JP (1) | JP2002542275A (en) |
BR (1) | BR0012735A (en) |
CA (1) | CA2369951A1 (en) |
DE (1) | DE19918434A1 (en) |
WO (1) | WO2000064414A2 (en) |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2003000292A1 (en) * | 2001-06-22 | 2003-01-03 | Pfizer Products Inc. | Pharmaceutical compositions comprising low-solubility and/or acid-sensitive drugs and neutralized acidic polymers |
WO2003000235A1 (en) * | 2001-06-22 | 2003-01-03 | Pfizer Products Inc. | Pharmaceutical compositions of dispersions of drugs and neutral polymers |
EP1827429A2 (en) * | 2004-12-20 | 2007-09-05 | Dr. Reddy's Laboratories Ltd. | Pharmaceutical compositions comprising amorphous benzimidazole compounds |
DE102017008656A1 (en) | 2017-09-15 | 2019-03-21 | Glatt Maschinen- Und Apparatebau Ag | Method for controlling the mass or volume flow of the atomizing gas of a nozzle; Apparatus for controlling the mass or volume flow of the atomizing gas of a nozzle; Use of a method or a device for controlling the mass or volume flow of the atomizing gas |
Families Citing this family (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU2001211213A1 (en) * | 2000-10-20 | 2002-04-29 | Galephar M/F | Stable oral formulation containing benzimidazole derivative |
EP1401399A2 (en) * | 2001-06-22 | 2004-03-31 | Pfizer Products Inc. | Pharmaceutical compositions containing polymer and drug assemblies |
WO2006066932A1 (en) * | 2004-12-24 | 2006-06-29 | Lek Pharmaceuticals D.D. | Stable pharmaceutical composition comprising an active substance in the form of solid solution |
GB2447572B (en) * | 2005-11-17 | 2011-06-01 | Jon Pty Ltd | Pharmacologically active disulfide compounds |
CN103126998A (en) * | 2007-09-28 | 2013-06-05 | 西梯茜生命工学股份有限公司 | Solid dispersion and pharmaceutical composition containing esomeprazole |
US8722636B2 (en) | 2011-01-31 | 2014-05-13 | New Market Pharmaceuticals, LLC | Animal treatments |
US10064849B2 (en) * | 2012-05-02 | 2018-09-04 | New Market Pharmaceuticals | Pharmaceutical compositions for direct systemic introduction |
AU2012379005B2 (en) | 2012-05-02 | 2017-12-21 | Newmarket Pharmaceuticals Llc | Pharmaceutical compositions for direct systemic introduction |
CA3081358A1 (en) * | 2017-11-10 | 2019-05-16 | Dispersol Technologies, Llc | Improved drug formulations |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0864324A1 (en) * | 1997-03-12 | 1998-09-16 | Basf Aktiengesellschaft | Method to produce solid combined pharmaceutical forms |
WO1998050019A1 (en) * | 1997-05-09 | 1998-11-12 | Sage Pharmaceuticals, Inc. | Stable oral pharmaceutical dosage forms |
-
1999
- 1999-04-23 DE DE19918434A patent/DE19918434A1/en not_active Withdrawn
-
2000
- 2000-04-11 EP EP00925201A patent/EP1173152A2/en not_active Withdrawn
- 2000-04-11 JP JP2000613405A patent/JP2002542275A/en not_active Withdrawn
- 2000-04-11 WO PCT/EP2000/003232 patent/WO2000064414A2/en not_active Application Discontinuation
- 2000-04-11 BR BR0012735-3A patent/BR0012735A/en active Pending
- 2000-04-11 CA CA002369951A patent/CA2369951A1/en not_active Abandoned
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0864324A1 (en) * | 1997-03-12 | 1998-09-16 | Basf Aktiengesellschaft | Method to produce solid combined pharmaceutical forms |
WO1998050019A1 (en) * | 1997-05-09 | 1998-11-12 | Sage Pharmaceuticals, Inc. | Stable oral pharmaceutical dosage forms |
Non-Patent Citations (1)
Title |
---|
SARISUTA N ET AL: "CRYSTALLINITY OF OMEPRAZOLE IN VARIOUS FILM POLYMERS" PHARMACY AND PHARMACOLOGY COMMUNICATIONS,LONDON,GB, Bd. 6, Januar 2000 (2000-01), Seiten 7-11, XP000946034 ISSN: 1460-8081 * |
Cited By (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2003000292A1 (en) * | 2001-06-22 | 2003-01-03 | Pfizer Products Inc. | Pharmaceutical compositions comprising low-solubility and/or acid-sensitive drugs and neutralized acidic polymers |
WO2003000235A1 (en) * | 2001-06-22 | 2003-01-03 | Pfizer Products Inc. | Pharmaceutical compositions of dispersions of drugs and neutral polymers |
US8147872B2 (en) | 2001-06-22 | 2012-04-03 | Bend Reseach, Inc. | Pharmaceutical compositions of drugs and neutralized acidic polymers |
US8173142B2 (en) | 2001-06-22 | 2012-05-08 | Bend Research, Inc. | Pharmaceutical compositions of drugs and neutralized acidic polymers |
US9468604B2 (en) | 2001-06-22 | 2016-10-18 | Bend Research, Inc. | Pharmaceutical compositions of dispersions of drug and neutral polymers |
EP1827429A2 (en) * | 2004-12-20 | 2007-09-05 | Dr. Reddy's Laboratories Ltd. | Pharmaceutical compositions comprising amorphous benzimidazole compounds |
EP1827429A4 (en) * | 2004-12-20 | 2009-08-05 | Reddys Lab Ltd Dr | Pharmaceutical compositions comprising amorphous benzimidazole compounds |
DE102017008656A1 (en) | 2017-09-15 | 2019-03-21 | Glatt Maschinen- Und Apparatebau Ag | Method for controlling the mass or volume flow of the atomizing gas of a nozzle; Apparatus for controlling the mass or volume flow of the atomizing gas of a nozzle; Use of a method or a device for controlling the mass or volume flow of the atomizing gas |
DE102017008656B4 (en) * | 2017-09-15 | 2020-12-03 | Glatt Maschinen- Und Apparatebau Ag | Method for controlling the mass or volume flow of the atomizing gas of a nozzle; Device for regulating the mass or volume flow of the atomizing gas of a nozzle; Use of a method or a device for regulating the mass or volume flow of the atomizer gas |
Also Published As
Publication number | Publication date |
---|---|
CA2369951A1 (en) | 2000-11-02 |
JP2002542275A (en) | 2002-12-10 |
DE19918434A1 (en) | 2000-10-26 |
BR0012735A (en) | 2005-02-22 |
WO2000064414A3 (en) | 2001-05-31 |
EP1173152A2 (en) | 2002-01-23 |
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