CA2503396C - Water-soluble meloxicam granules - Google Patents
Water-soluble meloxicam granules Download PDFInfo
- Publication number
- CA2503396C CA2503396C CA2503396A CA2503396A CA2503396C CA 2503396 C CA2503396 C CA 2503396C CA 2503396 A CA2503396 A CA 2503396A CA 2503396 A CA2503396 A CA 2503396A CA 2503396 C CA2503396 C CA 2503396C
- Authority
- CA
- Canada
- Prior art keywords
- meloxicam
- water soluble
- granules according
- meloxicam granules
- flavouring
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
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- ZRVUJXDFFKFLMG-UHFFFAOYSA-N Meloxicam Chemical compound OC=1C2=CC=CC=C2S(=O)(=O)N(C)C=1C(=O)NC1=NC=C(C)S1 ZRVUJXDFFKFLMG-UHFFFAOYSA-N 0.000 title claims abstract description 79
- 229960001929 meloxicam Drugs 0.000 title claims abstract description 76
- 239000008187 granular material Substances 0.000 title claims abstract description 55
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 30
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 claims abstract description 23
- 239000011230 binding agent Substances 0.000 claims abstract description 12
- 235000003599 food sweetener Nutrition 0.000 claims abstract description 12
- 239000003765 sweetening agent Substances 0.000 claims abstract description 12
- 238000000034 method Methods 0.000 claims abstract description 11
- 230000000241 respiratory effect Effects 0.000 claims abstract description 9
- 239000011734 sodium Substances 0.000 claims abstract description 8
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims abstract description 7
- 150000003839 salts Chemical class 0.000 claims abstract description 7
- 229910052708 sodium Inorganic materials 0.000 claims abstract description 7
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims abstract description 6
- 150000003863 ammonium salts Chemical class 0.000 claims abstract description 6
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 6
- 229910052700 potassium Inorganic materials 0.000 claims abstract description 6
- 239000011591 potassium Substances 0.000 claims abstract description 6
- 239000000546 pharmaceutical excipient Substances 0.000 claims abstract description 4
- 241001465754 Metazoa Species 0.000 claims description 12
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 claims description 11
- 229960001031 glucose Drugs 0.000 claims description 11
- 239000007788 liquid Substances 0.000 claims description 11
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 8
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 8
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 8
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 claims description 8
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 8
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 8
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 7
- 239000013543 active substance Substances 0.000 claims description 7
- 239000008103 glucose Substances 0.000 claims description 7
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 6
- 239000008101 lactose Substances 0.000 claims description 6
- 206010037660 Pyrexia Diseases 0.000 claims description 5
- 230000037396 body weight Effects 0.000 claims description 5
- 235000012907 honey Nutrition 0.000 claims description 5
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 claims description 4
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 claims description 4
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 claims description 4
- 206010061218 Inflammation Diseases 0.000 claims description 4
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 claims description 4
- 208000002193 Pain Diseases 0.000 claims description 4
- 235000009499 Vanilla fragrans Nutrition 0.000 claims description 4
- 244000263375 Vanilla tahitensis Species 0.000 claims description 4
- 235000012036 Vanilla tahitensis Nutrition 0.000 claims description 4
- 235000010358 acesulfame potassium Nutrition 0.000 claims description 4
- 230000004054 inflammatory process Effects 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 4
- 239000000600 sorbitol Substances 0.000 claims description 4
- 108010011485 Aspartame Proteins 0.000 claims description 3
- 239000000605 aspartame Substances 0.000 claims description 3
- 235000010357 aspartame Nutrition 0.000 claims description 3
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 claims description 3
- 229960003438 aspartame Drugs 0.000 claims description 3
- 238000000576 coating method Methods 0.000 claims description 3
- 238000010438 heat treatment Methods 0.000 claims description 3
- 229940069328 povidone Drugs 0.000 claims description 3
- 238000005507 spraying Methods 0.000 claims description 3
- 238000003756 stirring Methods 0.000 claims description 3
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims description 2
- 239000001828 Gelatine Substances 0.000 claims description 2
- 229930195725 Mannitol Natural products 0.000 claims description 2
- 229920002472 Starch Polymers 0.000 claims description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 claims description 2
- 229930006000 Sucrose Natural products 0.000 claims description 2
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 claims description 2
- 239000006052 feed supplement Substances 0.000 claims description 2
- 229920000159 gelatin Polymers 0.000 claims description 2
- 235000019322 gelatine Nutrition 0.000 claims description 2
- 235000001727 glucose Nutrition 0.000 claims description 2
- 230000007774 longterm Effects 0.000 claims description 2
- 239000000594 mannitol Substances 0.000 claims description 2
- 235000010355 mannitol Nutrition 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 claims description 2
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 claims description 2
- 239000008107 starch Substances 0.000 claims description 2
- 235000019698 starch Nutrition 0.000 claims description 2
- 239000005720 sucrose Substances 0.000 claims description 2
- 239000000811 xylitol Substances 0.000 claims description 2
- 235000010447 xylitol Nutrition 0.000 claims description 2
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 claims description 2
- 229960002675 xylitol Drugs 0.000 claims description 2
- 238000004806 packaging method and process Methods 0.000 claims 1
- 241000124008 Mammalia Species 0.000 abstract description 3
- 230000002757 inflammatory effect Effects 0.000 abstract description 2
- 239000003651 drinking water Substances 0.000 description 5
- 235000020188 drinking water Nutrition 0.000 description 5
- 206010012735 Diarrhoea Diseases 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 208000030175 lameness Diseases 0.000 description 3
- 229960003511 macrogol Drugs 0.000 description 3
- 208000004396 mastitis Diseases 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 230000000007 visual effect Effects 0.000 description 3
- WBZFUFAFFUEMEI-UHFFFAOYSA-M Acesulfame k Chemical compound [K+].CC1=CC(=O)[N-]S(=O)(=O)O1 WBZFUFAFFUEMEI-UHFFFAOYSA-M 0.000 description 2
- 241000283086 Equidae Species 0.000 description 2
- -1 N-methyl-D-glucamine salt Chemical class 0.000 description 2
- WINXNKPZLFISPD-UHFFFAOYSA-M Saccharin sodium Chemical compound [Na+].C1=CC=C2C(=O)[N-]S(=O)(=O)C2=C1 WINXNKPZLFISPD-UHFFFAOYSA-M 0.000 description 2
- 241000282887 Suidae Species 0.000 description 2
- 239000000619 acesulfame-K Substances 0.000 description 2
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 2
- 229910052782 aluminium Inorganic materials 0.000 description 2
- 239000004411 aluminium Substances 0.000 description 2
- 235000015872 dietary supplement Nutrition 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 239000007921 spray Substances 0.000 description 2
- 239000011550 stock solution Substances 0.000 description 2
- LICPKMHUPOIPDE-WZTVWXICSA-N 4-hydroxy-2-methyl-n-(5-methyl-1,3-thiazol-2-yl)-1,1-dioxo-1$l^{6},2-benzothiazine-3-carboxamide;(2r,3r,4r,5s)-6-(methylamino)hexane-1,2,3,4,5-pentol Chemical class CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO.OC=1C2=CC=CC=C2S(=O)(=O)N(C)C=1C(=O)NC1=NC=C(C)S1 LICPKMHUPOIPDE-WZTVWXICSA-N 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 239000012612 commercial material Substances 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 239000000428 dust Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 239000006193 liquid solution Substances 0.000 description 1
- 229960003194 meglumine Drugs 0.000 description 1
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000005022 packaging material Substances 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
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
-
- 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
- A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
- A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
-
- 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
- A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
- A61K31/5415—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame ortho- or peri-condensed with carbocyclic ring systems, e.g. phenothiazine, chlorpromazine, piroxicam
-
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
Abstract
The present invention relates to meloxicam granules which dissolve rapidly in water, containing meloxicam, a salt forming agent which forms the meglumin, sodium, potassium or ammonium salts of meloxicam, a binder, a sugar or sweetener, a carrier, optionally a flavouring and optionally other excipients, processes for preparing them and their use for treating respiratory or inflammatory complaints in mammals.
Description
Case I/1405-FF cz~ 02503396 2005-04-22 Boehringer Ingelheim Vetmedica GmbH
Water-soluble Meloxicam Granules The present invention relates to meloxicam granules which dissolve rapidly in water, containing meloxicam, a salt forming agent which forms the meglumine, sodium, potassium or ammonium salt of meloxicam, binders, a sugar or sweetener, a carrier, optionally a flavouring and optionally other excipients, processes for preparing them and their use for treating respiratory or inflammatory complaints in mammals.
Background to the Invention to Meloxicam (4-hydroxy-2-methyl-N-(5-methyl-2-thiazolyl)-2H-1,2-benzothiazine-3-carboxamide-1,1-dioxide) is an active substance which belongs to the group of NSAID's (non-steroidal-antiinflammatory drugs). Meloxicam and the sodium and meglumine salt thereof (N-methyl-D-glucamine salt) are described in EP-A-0 002 482. EP-A-0 I5 discloses the pH-dependent solubility characteristics of meloxicam and its salts, i.e. the sodium salt, the ammonium salt and the meglumine salt, in aqueous solution.
According to this, meloxicam is an active substance which does not dissolve readily in water. The meloxicam salts, particularly the meglumine salt, exhibit improved solubility as the pH
increases between 4 and 10, as shown in Table 1 of EP-0 945 134.
It is known that administering medicaments to sick animals, particularly those suffering from fever, can be done particularly easily and successively through their drinking water.
Administering to their food can also make it easier to give the medicament to the animal. It is known from EP 0945134 that meloxicam and meglumin cannot easily be compressed.
The 2s aim of the present invention is therefore to develop a granulated form of meloxicam which can be administered to the animals by mixing it into their drinking water or as a food supplement.
Description of the Invention Surprisingly, meloxicam granules have been discovered which can easily be produced by a fluidised bed method and which, when dissolved in water, form a drinking water solution which is stable over at least 48 hours. It was also found that these granules can be added to the animals food.
The invention therefore relates to water soluble granules containing meloxicam, a salt s forming agent which forms the meglumin, sodium, potassium or ammonium salt of meloxicam, binders, a sugar or sweetener, a carrier, optionally a flavouring and optionally other excipients.
The meloxicam granules according to the invention have a number of advantages over existing preparations.
In sick animals an increased uptake of drinking water can be observed when a drink containing meloxicam is given. Suitable dilution of the dissolved granules allows a variable, precise dosing of the active substance meloxicam. Because of the good solubility of the 15 meloxicam granules according to the invention in water the effects of meloxicam in the body of the sick animal set in very rapidly. The good flavour of the meloxicam granules also makes it possible to administer them as a food supplement. In addition the granules according to the invention have very good flow properties, a uniform meloxicam content, they are virtually free from dust and have a narrow particle size distribution of 125 ~m to 500 pm.
2o The total solubility of the granules in water ensures optical control of a totally dissolved active substance which is only available for therapeutic use in this form when administered in drinking water. In a preferred embodiment of the invention the salt forming agent is meglumin. In another preferred embodiment of the invention the binder may be selected from among hydroxypropyl-methylcellulose, polyvinylpyrrolidone, gelatine, starch and 2s polyethyleneglycolether, preferably hydroxypropyl-methylcellulose, polyvinylpyrrolidone and polyethyleneglycolether, most preferably hydroxypropyl-methylcellulose and polyvinylpyrrolidone.
In another preferred embodiment of the invention the sugar or sweetener may be selected 3o from among sodium saccharine, aspartame and Sunett~, preferably sodium saccharine or aspartame.
Particularly preferred according to the invention are meloxicam granules in which the flavouring is selected from among vanilla, honey flavouring, apple flavouring and contramarum, preferably honey flavouring and apple flavouring. Also particularly preferred are meloxicam granules in which the carrier is selected from among lactose, glucose, mannitol, xylitol, sucrose and sorbitol, preferably glucose, lactose or sorbitol, more preferably glucose orlactose, most preferably glucose.
Particularly preferred are meloxicam granules in which the content of meloxicam is between 0.05 % and 4 %, preferably between 0.1 and 2 %, preferably between 0.3 % and 1.5 %, more preferably between 0.4 % and 1 %, most preferably 0.6 %. Also particularly preferred are meloxicam granules which contain meglumin and meloxicam in a molar ratio of about 9:8 to 12:8, preferably 10:8.
The invention further relates to process for preparing the meloxicam granules according to the invention in which the steps a) to c) are carried out successively:
a) Preparing an aqueous granulating liquid containing binder, optionally a sugar or sweetener, meloxicam, meglumin and/or a flavouring.
b) Spraying the granulating liquid on to a carrier in a topspray fluidised bed method with an air current supplied at a constsnt temperature from 50 to 80 °C, preferably 65 °C.
c) A subsequent coating process with an aqueous granulating liquid by the topspray fluidised bed method containing a binder, a sugar or sweetener and/or a flavouring.
In a preferred process according to the invention the granulating liquid is prepared by stirring and heating the components to 70 to 100 °C, preferably about 90 °C.
A particular feature of the meloxicam granules according to he invention is that they have a long term stability of 24 months or more when stored in their original package at room temperature.
A particularly preferred granulated meloxicam preparation contains meloxicam, meglumin, hydroxypropylmethylcellulose, povidone and glucose monohydrate.
The present invention further relates to the use of meloxicam granules for preparing a pharmaceutical composition for treating pain, inflammation, fever, acute mastitis, diarrhoea, lameness, problems of mobility and respiratory complaints in animals, preferably acute mastitis, diarrhoea, lameness, mobility problems and respiratory complaints, preferably acute mastitis, diarrhoea, lameness, mobility problems and respiratory complaints, most preferably mobility problems or respiratory complaints. The treatment may be given in conjunction with antibiotic treatment.
The formulation according to the invention is suitable for treating animals, preferably mammals, particularly domestic pets or farm animals, such as pigs, horses, cattle, dogs or cats, preferably pigs or horses.
t o The meloxicam granules according to the invention are preferably used in amounts corresponing to a dosage range from 0.2 to 1.0 mg of active substance per kg of bodyweight, preferably 0.4 to 0.8 mg/kg of bodyweight, preferably 0.5 to 0.7 mg/kg of bodyweight, more preferably 0.6 mg/kg of bodyweight.
It is also preferable to use the meloxicam granules according to the invention to prepare a pharmaceutical composition which can be administered both in drink and also as a feed supplement.
The formulation according to the invention may contain, as the meloxicam salt, the 2o meglumin, sodium, potassium or ammonium salt, preferably the meloxicam meglumin salt.
The proportion of meglumin is between 0.035 and 2.8 %, preferably 0.07 to 1.4%, preferably 0.21-1.05 %, more preferably 0.28-0.7 % mg/g, particularly about 0.42 % in the meloxicam granules. The possible concentrations of sodium, potassium and ammonium may be calculated accordingly.
The concentration of the binder may be in the range from 20-80 mg/g, preferably 30-70 mg/g, preferably 40-60 mg/g, most preferably 50 mg/g of granules.
3o The concentration of the sugar may be in the range from 50-150 mg/g, preferably 75-125 mg/g, more preferably about 100 mg/g of granules.
The concentration of the sweetener may be in the range from 1-10 mg/g, preferably 2-5 mg/g, more preferably about 3 mg/g of granules.
The ceoncentration of the carrier may be in the range from 800-985 mglg, preferably 900-960 5 mg/g, more preferably about 930 mg/g of granules.
The concentration of the flavouring may be in the range from 0.1-10 mg/g, preferably 0.2-1.0 mg/g, more preferably about 0.5 mg/g of granules.
The packaging material used for the formulation according to the invention may be any of a number of standard commercial materials for granules. These include for example plastic containers, e.g. made of HPPE (High pressure polyethylene), aluminium bags or paper bags with an aluminium lining.
t 5 The meloxicam granules are produced by the top spray fluidised bed method.
In this, first of all an aqueous granulating liquid solution consisting of about 50 to 70 g/kg of binder, such as PVP 25000, hydroxypropylmethyl-cellulose or Macrogol 6000, preferably hydroxypropylmethyl-cellulose and/or about 1 to 5 g/kg of sweeteners such as Sunett~ or Na saccharine, preferably Sunett~, and/or about 0.5 to 2.5 g of flavouring, such as vanilla, honey, 2o flavouring 203180 or contramarum, preferably honey, about 10 to 15 g of meloxicam (peg milled) and about 7 to 11 g of meglumin is produced with stirring by heating to about 70 to 100 °C.
The granulating liquid is then sprayed on to a carrier such as lactose, glucose or sorbitol, 25 preferably glucose, by a counter flow process (Top Spray). This is done, for example, using a two-component nozzle, spraying at a constant air pressure at about 50 to 80 °C , preferably at about 65 °C. The coating process may then be carried out using a second aqueous granulating liquid. In order to prepare a solution ready for use a stock solution should be dissolved completely in water. Then the stock solution may be adjusted to the desired concentration for 3o use by mixing with water. To increase safety in use, the granules may have water soluble colour markings.
Water-soluble Meloxicam Granules The present invention relates to meloxicam granules which dissolve rapidly in water, containing meloxicam, a salt forming agent which forms the meglumine, sodium, potassium or ammonium salt of meloxicam, binders, a sugar or sweetener, a carrier, optionally a flavouring and optionally other excipients, processes for preparing them and their use for treating respiratory or inflammatory complaints in mammals.
Background to the Invention to Meloxicam (4-hydroxy-2-methyl-N-(5-methyl-2-thiazolyl)-2H-1,2-benzothiazine-3-carboxamide-1,1-dioxide) is an active substance which belongs to the group of NSAID's (non-steroidal-antiinflammatory drugs). Meloxicam and the sodium and meglumine salt thereof (N-methyl-D-glucamine salt) are described in EP-A-0 002 482. EP-A-0 I5 discloses the pH-dependent solubility characteristics of meloxicam and its salts, i.e. the sodium salt, the ammonium salt and the meglumine salt, in aqueous solution.
According to this, meloxicam is an active substance which does not dissolve readily in water. The meloxicam salts, particularly the meglumine salt, exhibit improved solubility as the pH
increases between 4 and 10, as shown in Table 1 of EP-0 945 134.
It is known that administering medicaments to sick animals, particularly those suffering from fever, can be done particularly easily and successively through their drinking water.
Administering to their food can also make it easier to give the medicament to the animal. It is known from EP 0945134 that meloxicam and meglumin cannot easily be compressed.
The 2s aim of the present invention is therefore to develop a granulated form of meloxicam which can be administered to the animals by mixing it into their drinking water or as a food supplement.
Description of the Invention Surprisingly, meloxicam granules have been discovered which can easily be produced by a fluidised bed method and which, when dissolved in water, form a drinking water solution which is stable over at least 48 hours. It was also found that these granules can be added to the animals food.
The invention therefore relates to water soluble granules containing meloxicam, a salt s forming agent which forms the meglumin, sodium, potassium or ammonium salt of meloxicam, binders, a sugar or sweetener, a carrier, optionally a flavouring and optionally other excipients.
The meloxicam granules according to the invention have a number of advantages over existing preparations.
In sick animals an increased uptake of drinking water can be observed when a drink containing meloxicam is given. Suitable dilution of the dissolved granules allows a variable, precise dosing of the active substance meloxicam. Because of the good solubility of the 15 meloxicam granules according to the invention in water the effects of meloxicam in the body of the sick animal set in very rapidly. The good flavour of the meloxicam granules also makes it possible to administer them as a food supplement. In addition the granules according to the invention have very good flow properties, a uniform meloxicam content, they are virtually free from dust and have a narrow particle size distribution of 125 ~m to 500 pm.
2o The total solubility of the granules in water ensures optical control of a totally dissolved active substance which is only available for therapeutic use in this form when administered in drinking water. In a preferred embodiment of the invention the salt forming agent is meglumin. In another preferred embodiment of the invention the binder may be selected from among hydroxypropyl-methylcellulose, polyvinylpyrrolidone, gelatine, starch and 2s polyethyleneglycolether, preferably hydroxypropyl-methylcellulose, polyvinylpyrrolidone and polyethyleneglycolether, most preferably hydroxypropyl-methylcellulose and polyvinylpyrrolidone.
In another preferred embodiment of the invention the sugar or sweetener may be selected 3o from among sodium saccharine, aspartame and Sunett~, preferably sodium saccharine or aspartame.
Particularly preferred according to the invention are meloxicam granules in which the flavouring is selected from among vanilla, honey flavouring, apple flavouring and contramarum, preferably honey flavouring and apple flavouring. Also particularly preferred are meloxicam granules in which the carrier is selected from among lactose, glucose, mannitol, xylitol, sucrose and sorbitol, preferably glucose, lactose or sorbitol, more preferably glucose orlactose, most preferably glucose.
Particularly preferred are meloxicam granules in which the content of meloxicam is between 0.05 % and 4 %, preferably between 0.1 and 2 %, preferably between 0.3 % and 1.5 %, more preferably between 0.4 % and 1 %, most preferably 0.6 %. Also particularly preferred are meloxicam granules which contain meglumin and meloxicam in a molar ratio of about 9:8 to 12:8, preferably 10:8.
The invention further relates to process for preparing the meloxicam granules according to the invention in which the steps a) to c) are carried out successively:
a) Preparing an aqueous granulating liquid containing binder, optionally a sugar or sweetener, meloxicam, meglumin and/or a flavouring.
b) Spraying the granulating liquid on to a carrier in a topspray fluidised bed method with an air current supplied at a constsnt temperature from 50 to 80 °C, preferably 65 °C.
c) A subsequent coating process with an aqueous granulating liquid by the topspray fluidised bed method containing a binder, a sugar or sweetener and/or a flavouring.
In a preferred process according to the invention the granulating liquid is prepared by stirring and heating the components to 70 to 100 °C, preferably about 90 °C.
A particular feature of the meloxicam granules according to he invention is that they have a long term stability of 24 months or more when stored in their original package at room temperature.
A particularly preferred granulated meloxicam preparation contains meloxicam, meglumin, hydroxypropylmethylcellulose, povidone and glucose monohydrate.
The present invention further relates to the use of meloxicam granules for preparing a pharmaceutical composition for treating pain, inflammation, fever, acute mastitis, diarrhoea, lameness, problems of mobility and respiratory complaints in animals, preferably acute mastitis, diarrhoea, lameness, mobility problems and respiratory complaints, preferably acute mastitis, diarrhoea, lameness, mobility problems and respiratory complaints, most preferably mobility problems or respiratory complaints. The treatment may be given in conjunction with antibiotic treatment.
The formulation according to the invention is suitable for treating animals, preferably mammals, particularly domestic pets or farm animals, such as pigs, horses, cattle, dogs or cats, preferably pigs or horses.
t o The meloxicam granules according to the invention are preferably used in amounts corresponing to a dosage range from 0.2 to 1.0 mg of active substance per kg of bodyweight, preferably 0.4 to 0.8 mg/kg of bodyweight, preferably 0.5 to 0.7 mg/kg of bodyweight, more preferably 0.6 mg/kg of bodyweight.
It is also preferable to use the meloxicam granules according to the invention to prepare a pharmaceutical composition which can be administered both in drink and also as a feed supplement.
The formulation according to the invention may contain, as the meloxicam salt, the 2o meglumin, sodium, potassium or ammonium salt, preferably the meloxicam meglumin salt.
The proportion of meglumin is between 0.035 and 2.8 %, preferably 0.07 to 1.4%, preferably 0.21-1.05 %, more preferably 0.28-0.7 % mg/g, particularly about 0.42 % in the meloxicam granules. The possible concentrations of sodium, potassium and ammonium may be calculated accordingly.
The concentration of the binder may be in the range from 20-80 mg/g, preferably 30-70 mg/g, preferably 40-60 mg/g, most preferably 50 mg/g of granules.
3o The concentration of the sugar may be in the range from 50-150 mg/g, preferably 75-125 mg/g, more preferably about 100 mg/g of granules.
The concentration of the sweetener may be in the range from 1-10 mg/g, preferably 2-5 mg/g, more preferably about 3 mg/g of granules.
The ceoncentration of the carrier may be in the range from 800-985 mglg, preferably 900-960 5 mg/g, more preferably about 930 mg/g of granules.
The concentration of the flavouring may be in the range from 0.1-10 mg/g, preferably 0.2-1.0 mg/g, more preferably about 0.5 mg/g of granules.
The packaging material used for the formulation according to the invention may be any of a number of standard commercial materials for granules. These include for example plastic containers, e.g. made of HPPE (High pressure polyethylene), aluminium bags or paper bags with an aluminium lining.
t 5 The meloxicam granules are produced by the top spray fluidised bed method.
In this, first of all an aqueous granulating liquid solution consisting of about 50 to 70 g/kg of binder, such as PVP 25000, hydroxypropylmethyl-cellulose or Macrogol 6000, preferably hydroxypropylmethyl-cellulose and/or about 1 to 5 g/kg of sweeteners such as Sunett~ or Na saccharine, preferably Sunett~, and/or about 0.5 to 2.5 g of flavouring, such as vanilla, honey, 2o flavouring 203180 or contramarum, preferably honey, about 10 to 15 g of meloxicam (peg milled) and about 7 to 11 g of meglumin is produced with stirring by heating to about 70 to 100 °C.
The granulating liquid is then sprayed on to a carrier such as lactose, glucose or sorbitol, 25 preferably glucose, by a counter flow process (Top Spray). This is done, for example, using a two-component nozzle, spraying at a constant air pressure at about 50 to 80 °C , preferably at about 65 °C. The coating process may then be carried out using a second aqueous granulating liquid. In order to prepare a solution ready for use a stock solution should be dissolved completely in water. Then the stock solution may be adjusted to the desired concentration for 3o use by mixing with water. To increase safety in use, the granules may have water soluble colour markings.
The meloxicam granules according to the invention will be illustrated by the examples that follows. The skilled man will be aware that this example is intended solely as an illustration and should not be regarded as limiting.
Example 1 0.6% meloxicam granules Recipe:
g/ 100 g to Meloxicam 0.6 Meglumin 0.42 Hydroxypropylmethylcellulose3.00 Povidone 2.00 Glucose monohydrate 93.98 Example 2 1.2% meloxicam granules Meloxicam 1.2 Meglumin 0.84 2o Hydroxypropylmethylcellulose3.00 Collidone 25 2.0 Glucose Monohydrate 92.96 Example 3 0.6% meloxicam ranules Meloxicam 0.6 Meglumin 0.42 Pharmacoat 606 4.0 Macrogol 6000 1.0 3o Acesulfame K 0.3 Lactose 93.68 Example 4 0.6% meloxicam granules Meloxicam 0.6 Meglumin 0.42 s Pharmacoat 606 4.75 Macrogol 6000 0.25 Acesulfame K 0.3 Liquid vanilla flavouring0.05 Lactose 93.63 Bright yellow free flowing meloxicam granules corresponding to Examples 1 to 4 may be prepared as follows:
~ 5 The granules are stored for 3 months at 25 °C at a relative humidity of 60 %. No significant changes were observed in terms of the active substance content, the water content (according to Karl-Fischer), the visual solubility characteristics, the pH in demineralised water and the visual wettability. In order to determine the visual solubility characteristics, 5 g of the granules were dissolved in 100 ml of demineralised water at ambient temperature. After 2o about 1 min a clear yellowish solution was obtained.
Example 1 0.6% meloxicam granules Recipe:
g/ 100 g to Meloxicam 0.6 Meglumin 0.42 Hydroxypropylmethylcellulose3.00 Povidone 2.00 Glucose monohydrate 93.98 Example 2 1.2% meloxicam granules Meloxicam 1.2 Meglumin 0.84 2o Hydroxypropylmethylcellulose3.00 Collidone 25 2.0 Glucose Monohydrate 92.96 Example 3 0.6% meloxicam ranules Meloxicam 0.6 Meglumin 0.42 Pharmacoat 606 4.0 Macrogol 6000 1.0 3o Acesulfame K 0.3 Lactose 93.68 Example 4 0.6% meloxicam granules Meloxicam 0.6 Meglumin 0.42 s Pharmacoat 606 4.75 Macrogol 6000 0.25 Acesulfame K 0.3 Liquid vanilla flavouring0.05 Lactose 93.63 Bright yellow free flowing meloxicam granules corresponding to Examples 1 to 4 may be prepared as follows:
~ 5 The granules are stored for 3 months at 25 °C at a relative humidity of 60 %. No significant changes were observed in terms of the active substance content, the water content (according to Karl-Fischer), the visual solubility characteristics, the pH in demineralised water and the visual wettability. In order to determine the visual solubility characteristics, 5 g of the granules were dissolved in 100 ml of demineralised water at ambient temperature. After 2o about 1 min a clear yellowish solution was obtained.
Claims (18)
1. Water soluble meloxicam granules containing meloxicam, a binder, a sugar or sweetener, a carrier, a salt forming agent which forms the meglumin, sodium, potassium or ammonium salt of meloxicam, optionally a flavouring and optionally other excipients.
2. Water soluble meloxicam granules according to claims 1, wherein the salt forming agent is meglumin.
3. Water soluble meloxicam granules according to claim 1 or 2, wherein the binder is selected from among hydroxypropyl-methylcellulose, polyvinylpyrrolidone, gelatine, starch and polyethyleneglycolether.
4. Water soluble meloxicam granules according to any one of claims 1 to 3, wherein the sugar or sweetener is selected from among sodium saccharine, aspartame and Sunett®.
5. Water soluble meloxicam granules according to any one of claims 1 to 4, wherein the flavouring is selected from among vanilla, honey flavouring, apple flavouring and contramarum.
6. Water soluble meloxicam granules according to any one of claims 1 to 5, wherein the carrier is selected from among lactose, glucose, mannitol, xylitol, sucrose and sorbitol.
7. Water soluble meloxicam granules according to any one of claims 1 to 6, wherein the proportion of meloxicam is between 0.05% and 4%.
8. Water soluble meloxicam granules according to any one of claims 1 to 7, which contain meglumin and meloxicam in a molar ratio of 9:8 to 12:8.
9. Water soluble meloxicam granules according to any one of claims 1 to 8, which contain meglumin and meloxicam in a molar ratio of 10:8.
10. Process for preparing the water soluble meloxicam granules according to any one of claims 1 to 9, comprising the steps a) to c) which are carried out successively:
a) preparing an aqueous granulating liquid containing a binder, a sugar or sweetener, meloxicam, megiumin and/or a flavouring;
b) spraying the granuiating liquid on to a carrier in a topspray fluidised bed method with a supply of air at a constant temperature of 50 to 80°C; and c) a subsequent coating process with an aqueous granulating liquid by the topspray fluidised bed method containing a binder, a sugar or sweetener and/or a flavouring.
a) preparing an aqueous granulating liquid containing a binder, a sugar or sweetener, meloxicam, megiumin and/or a flavouring;
b) spraying the granuiating liquid on to a carrier in a topspray fluidised bed method with a supply of air at a constant temperature of 50 to 80°C; and c) a subsequent coating process with an aqueous granulating liquid by the topspray fluidised bed method containing a binder, a sugar or sweetener and/or a flavouring.
11. Process according to claim 10, wherein the granulating liquid is prepared by stirring and heating the components to 70 to 100°C.
12. Water soluble meloxicam granules according to any one of claims 1-9, which have a long term stability of 24 months or longer when stored at ambient temperature in their original packaging.
13. Water soluble meloxicam granules according to any one of claims 1-9 or claim 12, containing meloxicam, meglumin, hydroxypropylmethylcellulose, povidone and glucose monohydrate.
14. Use of water soluble meloxicam granules according to any one of claims 1 to 9 or claim 12 for preparing a pharmaceutical composition for the treatment of pain, inflammation, fever or a respiratory complaint in an animal.
15. Use of water soluble meloxicam granules according to claim 13, which corresponds to a dosage range of from 0.2 to 1.0 mg of active substance per kg of bodyweight.
16. Use of water soluble meloxicam granules according to claim 12 or 13 for prepraring a pharmaceutical composition which can be administered both in drink and feed supplements.
17. Water soluble meloxicam granules according to any one of claims 1 to 9 or claim 12 or 13, for use in the treatment of pain, inflammation, fever or a respiratory complaint in an animal.
18. Use of meloxicam in water soluble meloxicam granules as defined in claim 1, 2, 3, 4, 5, 6, 7, 8, 9, 12 or 13 for the treatment of pain, inflammation, fever or a respiratory complaint in an animal.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE10250081A DE10250081A1 (en) | 2002-10-25 | 2002-10-25 | Water-soluble meloxicam granules |
| DE10250081.9 | 2002-10-25 | ||
| PCT/EP2003/011802 WO2004037264A1 (en) | 2002-10-25 | 2003-10-24 | Water-soluble meloxicam granulates |
Publications (2)
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|---|---|
| CA2503396A1 CA2503396A1 (en) | 2004-05-06 |
| CA2503396C true CA2503396C (en) | 2011-12-13 |
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|---|---|---|---|
| CA2503396A Expired - Lifetime CA2503396C (en) | 2002-10-25 | 2003-10-24 | Water-soluble meloxicam granules |
Country Status (28)
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| US (1) | US20130005714A1 (en) |
| EP (1) | EP1558262B1 (en) |
| JP (2) | JP4856377B2 (en) |
| KR (1) | KR101152689B1 (en) |
| CN (1) | CN1708307B (en) |
| AR (1) | AR041717A1 (en) |
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| AU (1) | AU2003276170B2 (en) |
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| CA (1) | CA2503396C (en) |
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| HR (1) | HRP20050366B1 (en) |
| MX (1) | MXPA05004211A (en) |
| MY (1) | MY136901A (en) |
| PE (1) | PE20040495A1 (en) |
| PL (1) | PL212425B1 (en) |
| PT (1) | PT1558262E (en) |
| RU (1) | RU2333744C2 (en) |
| TW (1) | TWI336622B (en) |
| UA (1) | UA81785C2 (en) |
| UY (1) | UY28039A1 (en) |
| WO (1) | WO2004037264A1 (en) |
| ZA (1) | ZA200502702B (en) |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20020035107A1 (en) | 2000-06-20 | 2002-03-21 | Stefan Henke | Highly concentrated stable meloxicam solutions |
| DE10161077A1 (en) | 2001-12-12 | 2003-06-18 | Boehringer Ingelheim Vetmed | Highly concentrated stable meloxicam solutions for needleless injection |
| DE10250081A1 (en) * | 2002-10-25 | 2004-05-13 | Boehringer Ingelheim Vetmedica Gmbh | Water-soluble meloxicam granules |
| US8992980B2 (en) | 2002-10-25 | 2015-03-31 | Boehringer Ingelheim Vetmedica Gmbh | Water-soluble meloxicam granules |
| EP1568369A1 (en) * | 2004-02-23 | 2005-08-31 | Boehringer Ingelheim Vetmedica Gmbh | Use of meloxicam for the treatment of respiratory diseases in pigs |
| DE102004030409A1 (en) * | 2004-06-23 | 2006-01-26 | Boehringer Ingelheim Vetmedica Gmbh | New use of meloxicam in veterinary medicine |
| CN1680427B (en) * | 2005-02-01 | 2010-08-11 | 杨喜鸿 | Water soluble piduomode composite salt and its preparation |
| WO2007011349A1 (en) * | 2005-07-15 | 2007-01-25 | Teva Pharmaceutical Industries Ltd. | Novel granulation process and granulate produced therefrom |
| BRPI0617208A2 (en) * | 2005-09-30 | 2011-07-19 | Boehringer Ingelheim Vetmed | pharmaceutical preparation containing meloxicam |
| US7572641B2 (en) | 2005-11-22 | 2009-08-11 | Teva Pharmaceutical Industries Ltd. | Pharmaceutical compositions comprising meloxicam and methods of their preparation |
| US7772255B2 (en) * | 2005-12-13 | 2010-08-10 | Supratek Pharma, Inc. | Method of treating tumors with azaxanthones |
| KR100791160B1 (en) * | 2006-05-30 | 2008-01-02 | 조선대학교산학협력단 | Ethanolamine salt of meloxicam and its pharmaceutical compositions |
| JP2010083826A (en) * | 2008-10-01 | 2010-04-15 | Nihon Generic Co Ltd | Method for producing solid preparation containing oxicam-based compound |
| TR200809200A1 (en) * | 2008-12-01 | 2009-12-21 | Sanovel �La� Sanay� Ve T�Caret Anon�M ��Rket� | Pharmaceutical formulations containing meloxicam |
| WO2011046853A1 (en) | 2009-10-12 | 2011-04-21 | Boehringer Ingelheim Vetmedica Gmbh | Containers for compositions comprising meloxicam |
| SG183846A1 (en) | 2010-03-03 | 2012-10-30 | Boehringer Ingelheim Vetmed | Use of meloxicam for the long-term treatment of musculoskeletal disorders in cats |
| US9795568B2 (en) | 2010-05-05 | 2017-10-24 | Boehringer Ingelheim Vetmedica Gmbh | Low concentration meloxicam tablets |
| RU2465892C1 (en) * | 2011-09-21 | 2012-11-10 | Федеральное государственное бюджетное образовательное учреждение высшего профессионального образования "Новосибирский национальный исследовательский государственный университет (НГУ)" | Method of obtaining highly dispersed meloxicame |
| CN103705479B (en) * | 2012-09-29 | 2017-11-28 | 瑞普（天津）生物药业有限公司 | A kind of pet Meloxicam sustained release tablets and preparation method thereof |
| RU2559000C1 (en) * | 2014-02-25 | 2015-08-10 | Вячеслав Михайлович Спиридонов | Bfk fodder additive |
| US9526734B2 (en) * | 2014-06-09 | 2016-12-27 | Iceutica Pty Ltd. | Formulation of meloxicam |
| WO2016086114A1 (en) * | 2014-11-25 | 2016-06-02 | Artdem, Llc | Sports drink formulation |
| US20170281640A1 (en) * | 2016-04-04 | 2017-10-05 | Productos Maver, S.A. De C.V. | Pharmaceutical Compositions Containing a Muscle Relaxant and a Nonsteroidal Anti-Inflammatory Drugs (NSAID) |
| CN109983013A (en) * | 2016-11-18 | 2019-07-05 | 帕西拉制药有限公司 | Meloxicam zinc complexes particle multivesicular liposome preparation and preparation method thereof |
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|---|---|---|---|---|
| JPS52102416A (en) * | 1976-02-19 | 1977-08-27 | Okawara Mfg | Granule making method of herb medicine and like |
| DE3218150C2 (en) * | 1982-05-14 | 1986-09-25 | Akzo Gmbh, 5600 Wuppertal | Active substance-containing body for long-term release and process for its production |
| JPH0753663B2 (en) * | 1984-10-09 | 1995-06-07 | 武田薬品工業株式会社 | Thiamine salt granules, their production and tablets |
| US5654003A (en) * | 1992-03-05 | 1997-08-05 | Fuisz Technologies Ltd. | Process and apparatus for making tablets and tablets made therefrom |
| JPH0912426A (en) * | 1995-06-29 | 1997-01-14 | Asahi Chem Ind Co Ltd | Hygroscopic material composition |
| EP0945134A1 (en) * | 1998-03-27 | 1999-09-29 | Boehringer Ingelheim Pharma KG | New galenic formulations of meloxicam for oral administration |
| US6106862A (en) * | 1998-08-13 | 2000-08-22 | Andrx Corporation | Once daily analgesic tablet |
| DE19859636A1 (en) * | 1998-12-23 | 2000-06-29 | Hexal Ag | Controlled release pharmaceutical composition with tilidine mesylate as active ingredient |
| US6685928B2 (en) * | 1999-12-07 | 2004-02-03 | Rutgers, The State University Of New Jersey | Therapeutic compositions and methods |
| AU2001262731A1 (en) * | 2000-06-20 | 2002-01-02 | Fujisawa Pharmaceutical Co. Ltd. | Tetracyclic compounds-containing pharmaceutical preparations |
| DE10030345A1 (en) * | 2000-06-20 | 2002-01-10 | Boehringer Ingelheim Vetmed | Highly concentrated stable meloxicam solutions |
| DE10250081A1 (en) * | 2002-10-25 | 2004-05-13 | Boehringer Ingelheim Vetmedica Gmbh | Water-soluble meloxicam granules |
-
2002
- 2002-10-25 DE DE10250081A patent/DE10250081A1/en not_active Withdrawn
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2003
- 2003-10-23 PE PE2003001075A patent/PE20040495A1/en not_active Application Discontinuation
- 2003-10-24 DE DE50308863T patent/DE50308863D1/en not_active Expired - Lifetime
- 2003-10-24 WO PCT/EP2003/011802 patent/WO2004037264A1/en active IP Right Grant
- 2003-10-24 PL PL375479A patent/PL212425B1/en unknown
- 2003-10-24 MX MXPA05004211A patent/MXPA05004211A/en active IP Right Grant
- 2003-10-24 JP JP2004545974A patent/JP4856377B2/en not_active Expired - Lifetime
- 2003-10-24 EP EP03809321A patent/EP1558262B1/en not_active Expired - Lifetime
- 2003-10-24 BR BR0315639-7A patent/BR0315639A/en active Pending
- 2003-10-24 DK DK03809321T patent/DK1558262T3/en active
- 2003-10-24 RU RU2005115955/15A patent/RU2333744C2/en active
- 2003-10-24 PT PT03809321T patent/PT1558262E/en unknown
- 2003-10-24 KR KR1020057006998A patent/KR101152689B1/en active IP Right Grant
- 2003-10-24 TW TW092129614A patent/TWI336622B/en not_active IP Right Cessation
- 2003-10-24 UY UY28039A patent/UY28039A1/en not_active Application Discontinuation
- 2003-10-24 CN CN2003801019791A patent/CN1708307B/en not_active Expired - Lifetime
- 2003-10-24 AU AU2003276170A patent/AU2003276170B2/en not_active Expired
- 2003-10-24 AT AT03809321T patent/ATE381337T1/en active
- 2003-10-24 AR ARP030103888A patent/AR041717A1/en not_active Application Discontinuation
- 2003-10-24 UA UAA200504878A patent/UA81785C2/en unknown
- 2003-10-24 ES ES03809321T patent/ES2298619T3/en not_active Expired - Lifetime
- 2003-10-24 CA CA2503396A patent/CA2503396C/en not_active Expired - Lifetime
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- 2005-04-22 HR HRP20050366AA patent/HRP20050366B1/en not_active IP Right Cessation
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2006
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