AR091707A1 - STABILIZED FORMULATIONS OF ETANERCEPT - Google Patents
STABILIZED FORMULATIONS OF ETANERCEPTInfo
- Publication number
- AR091707A1 AR091707A1 ARP130102430A AR091707A1 AR 091707 A1 AR091707 A1 AR 091707A1 AR P130102430 A ARP130102430 A AR P130102430A AR 091707 A1 AR091707 A1 AR 091707A1
- Authority
- AR
- Argentina
- Prior art keywords
- sodium chloride
- formulation
- meglumine
- etanercept
- combination
- Prior art date
Links
- 239000000203 mixture Substances 0.000 title abstract 12
- 108010008165 Etanercept Proteins 0.000 title abstract 6
- 229960000403 etanercept Drugs 0.000 title abstract 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 abstract 14
- 238000009472 formulation Methods 0.000 abstract 7
- 239000011780 sodium chloride Substances 0.000 abstract 7
- 239000004094 surface-active agent Substances 0.000 abstract 7
- 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 abstract 6
- 229960003194 meglumine Drugs 0.000 abstract 6
- 239000003381 stabilizer Substances 0.000 abstract 6
- 239000002245 particle Substances 0.000 abstract 5
- 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 abstract 4
- 229930006000 Sucrose Natural products 0.000 abstract 4
- 239000005720 sucrose Substances 0.000 abstract 4
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 abstract 3
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 abstract 3
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 abstract 3
- 239000000811 xylitol Substances 0.000 abstract 3
- 229960002675 xylitol Drugs 0.000 abstract 3
- 235000010447 xylitol Nutrition 0.000 abstract 3
- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 abstract 2
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 abstract 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 abstract 2
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 abstract 2
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 abstract 2
- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 abstract 2
- 229930195712 glutamate Natural products 0.000 abstract 2
- 238000000034 method Methods 0.000 abstract 2
- 229960000502 poloxamer Drugs 0.000 abstract 2
- 229920001983 poloxamer Polymers 0.000 abstract 2
- 229950008882 polysorbate Drugs 0.000 abstract 2
- 229920000136 polysorbate Polymers 0.000 abstract 2
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 abstract 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 abstract 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 abstract 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 abstract 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 abstract 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 abstract 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 abstract 1
- 150000001413 amino acids Chemical class 0.000 abstract 1
- 229910052791 calcium Inorganic materials 0.000 abstract 1
- 239000011575 calcium Substances 0.000 abstract 1
- 230000007774 longterm Effects 0.000 abstract 1
- 229910052749 magnesium Inorganic materials 0.000 abstract 1
- 239000011777 magnesium Substances 0.000 abstract 1
- 229910001629 magnesium chloride Inorganic materials 0.000 abstract 1
- 229910021645 metal ion Inorganic materials 0.000 abstract 1
- 239000008194 pharmaceutical composition Substances 0.000 abstract 1
- 229920005862 polyol Polymers 0.000 abstract 1
- 150000003077 polyols Chemical class 0.000 abstract 1
- 230000000087 stabilizing effect Effects 0.000 abstract 1
- 230000008646 thermal stress Effects 0.000 abstract 1
- 229910052725 zinc Inorganic materials 0.000 abstract 1
- 239000011701 zinc Substances 0.000 abstract 1
Landscapes
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
Abstract
Reivindicación 1: Una composición farmacéutica, caracterizada porque comprende etanercept y un estabilizante seleccionado del grupo que consiste en (i) un aminoácido seleccionado del grupo que consiste en serina, prolina y glutamato; (ii) un ión de metal seleccionado del grupo que consiste en calcio, magnesio y zinc; (iii) un estabilizante de xilitol seleccionado entre xilitol, solo, o una combinación de xilitol y meglumina; (iv) un estabilizante de cloruro de sodio seleccionado entre cloruro de sodio solo; cloruro de sodio en combinación con sacarosa o trehalosa, y la combinación de cloruro de sodio, sacarosa y trehalosa; (v) un estabilizante de meglumina seleccionado entre meglumina sola; meglumina en combinación con sacarosa; meglumina en combinación con cloruro de sodio; y meglumina con cloruro de sodio y sacarosa; y (vi) la combinación de un azúcar y un poliol, en donde el estabilizante mejora la estabilidad a largo plazo del etanercept. Reivindicación 2: La composición de la reivindicación 1, caracterizada porque además comprende un agente tensioactivo para prevenir, inhibir o reducir la aparición de partículas menores que las visibles en la composición, en donde el agente tensioactivo se selecciona del grupo que consiste en agentes tensioactivos de polisorbato y agentes tensioactivos de poloxámeros, y permite lograr una reducción significativa de las partículas menores que las visibles en la composición en comparación con una composición de etanercept que no contiene un agente tensioactivo. Reivindicación 10: Un método para estabilizar una formulación de etanercept y reducir la cantidad de partículas menores que las visibles en dicha formulación, caracterizado porque dicho método comprende los pasos de: a) agregar un agente tensioactivo de un polisorbato o de un poloxámero a una formulación de etanercept en una cantidad que constituye entre aproximadamente 0,0001 y aproximadamente 0,5% p/v de la formulación de manera tal que la cantidad de partículas menores que las visibles por ml de la formulación de un tamaño de entre aproximadamente 1 y 10 mm, se reduce en al menos un 50%, y preferiblemente en al menos aproximadamente un 70%, en comparación con la misma formulación preparada en la ausencia de dicho agente tensioactivo; donde la cantidad de partículas menores que las visibles se mide mediante un análisis por FIowCAM conducido en el momento de preparar la formulación y antes de cualquier almacenamiento o estrés térmico apreciable de la misma; b) agregar un estabilizante seleccionado del grupo que consiste en glutamato, cloruro de magnesio y cloruro de sodio.Claim 1: A pharmaceutical composition, characterized in that it comprises etanercept and a stabilizer selected from the group consisting of (i) an amino acid selected from the group consisting of serine, proline and glutamate; (ii) a metal ion selected from the group consisting of calcium, magnesium and zinc; (iii) a xylitol stabilizer selected from xylitol, alone, or a combination of xylitol and meglumine; (iv) a sodium chloride stabilizer selected from sodium chloride alone; sodium chloride in combination with sucrose or trehalose, and the combination of sodium chloride, sucrose and trehalose; (v) a meglumine stabilizer selected from meglumine alone; meglumine in combination with sucrose; meglumine in combination with sodium chloride; and meglumine with sodium chloride and sucrose; and (vi) the combination of a sugar and a polyol, wherein the stabilizer improves the long-term stability of etanercept. Claim 2: The composition of claim 1, characterized in that it further comprises a surfactant to prevent, inhibit or reduce the appearance of particles smaller than those visible in the composition, wherein the surfactant is selected from the group consisting of surfactants of polysorbate and poloxamer surfactants, and allows to achieve a significant reduction in particles smaller than those visible in the composition compared to an etanercept composition that does not contain a surfactant. Claim 10: A method for stabilizing a etanercept formulation and reducing the amount of particles smaller than those visible in said formulation, characterized in that said method comprises the steps of: a) adding a surfactant of a polysorbate or a poloxamer to a formulation of etanercept in an amount that constitutes between about 0.0001 and about 0.5% w / v of the formulation such that the amount of particles smaller than those visible per ml of the formulation of a size between about 1 and 10 mm, is reduced by at least 50%, and preferably by at least about 70%, compared to the same formulation prepared in the absence of said surfactant; where the amount of particles smaller than the visible ones is measured by an analysis by FIowCAM conducted at the time of preparing the formulation and before any appreciable storage or thermal stress thereof; b) add a stabilizer selected from the group consisting of glutamate, magnesium chloride and sodium chloride.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201261669480P | 2012-07-09 | 2012-07-09 | |
| US201361770429P | 2013-02-28 | 2013-02-28 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AR091707A1 true AR091707A1 (en) | 2015-02-25 |
Family
ID=50691535
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ARP130102430 AR091707A1 (en) | 2012-07-09 | 2013-07-08 | STABILIZED FORMULATIONS OF ETANERCEPT |
Country Status (2)
| Country | Link |
|---|---|
| AR (1) | AR091707A1 (en) |
| UY (1) | UY34895A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114929233A (en) * | 2019-11-12 | 2022-08-19 | 美国瑞根特有限公司 | Phosphodiesterase type V inhibitor compositions, methods of making them, and methods of using them |
-
2013
- 2013-07-08 AR ARP130102430 patent/AR091707A1/en unknown
- 2013-07-08 UY UY34895A patent/UY34895A/en not_active Application Discontinuation
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114929233A (en) * | 2019-11-12 | 2022-08-19 | 美国瑞根特有限公司 | Phosphodiesterase type V inhibitor compositions, methods of making them, and methods of using them |
Also Published As
| Publication number | Publication date |
|---|---|
| UY34895A (en) | 2014-02-28 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FB | Suspension of granting procedure |