ES2548706T3 - Nanosuspensión farmacéutica - Google Patents
Nanosuspensión farmacéutica Download PDFInfo
- Publication number
- ES2548706T3 ES2548706T3 ES12779018.6T ES12779018T ES2548706T3 ES 2548706 T3 ES2548706 T3 ES 2548706T3 ES 12779018 T ES12779018 T ES 12779018T ES 2548706 T3 ES2548706 T3 ES 2548706T3
- Authority
- ES
- Spain
- Prior art keywords
- nanosuspension
- flubendazole
- hours
- particle size
- drinking water
- 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.)
- Active
Links
- 239000006070 nanosuspension Substances 0.000 title description 8
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 abstract description 3
- 239000004480 active ingredient Substances 0.000 abstract 1
- 239000013078 crystal Substances 0.000 abstract 1
- 239000007971 pharmaceutical suspension Substances 0.000 abstract 1
- 239000004094 surface-active agent Substances 0.000 abstract 1
- CPEUVMUXAHMANV-UHFFFAOYSA-N flubendazole Chemical compound C1=C2NC(NC(=O)OC)=NC2=CC=C1C(=O)C1=CC=C(F)C=C1 CPEUVMUXAHMANV-UHFFFAOYSA-N 0.000 description 9
- 229960004500 flubendazole Drugs 0.000 description 9
- WNLRTRBMVRJNCN-UHFFFAOYSA-N adipic acid Chemical compound OC(=O)CCCCC(O)=O WNLRTRBMVRJNCN-UHFFFAOYSA-N 0.000 description 6
- 239000003651 drinking water Substances 0.000 description 6
- 235000020188 drinking water Nutrition 0.000 description 6
- 239000002245 particle Substances 0.000 description 6
- 238000010790 dilution Methods 0.000 description 4
- 239000012895 dilution Substances 0.000 description 4
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 4
- 239000001361 adipic acid Substances 0.000 description 3
- 235000011037 adipic acid Nutrition 0.000 description 3
- 210000002445 nipple Anatomy 0.000 description 3
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 2
- QCWXUUIWCKQGHC-UHFFFAOYSA-N Zirconium Chemical compound [Zr] QCWXUUIWCKQGHC-UHFFFAOYSA-N 0.000 description 2
- 230000000507 anthelmentic effect Effects 0.000 description 2
- 239000011324 bead Substances 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000002105 nanoparticle Substances 0.000 description 2
- 239000002736 nonionic surfactant Substances 0.000 description 2
- 229920000136 polysorbate Polymers 0.000 description 2
- 239000001384 succinic acid Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 238000011287 therapeutic dose Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 229910052726 zirconium Inorganic materials 0.000 description 2
- 241000282887 Suidae Species 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 239000002159 nanocrystal Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—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
- 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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/12—Carboxylic acids; Salts or anhydrides thereof
-
- 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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
-
- 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
- A61K9/10—Dispersions; Emulsions
-
- 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
-
- 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
- A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
- A61K9/145—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
- A61P33/14—Ectoparasiticides, e.g. scabicides
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Dispersion Chemistry (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Organic Chemistry (AREA)
- Tropical Medicine & Parasitology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
Una suspensión farmacéutica que comprende un tensioactivo y cocristales de tamaño nanométrico de al menos un ingrediente activo y al menos un ácido dicarboxílico.
Description
E12779018
29-09-2015
citan varias publicaciones. La descripción de estas publicaciones se incorpora de este modo como referencia en esta solicitud para describir totalmente el estado de la técnica a la que pertenece esta invención.
5
Ejemplo 1: Formación del cocristal de ácido adípico y flubendazol
A. Preparación de la nanosuspensión
10 Primero:
0,25 g Flubendazol (antihelmíntico basado en bencimidazol), 0,4 g ácido adípico (un ácido dicarboxílico), y 0,0625 g Tween® 80 (un agente tensoactivo no iónico)
15 se dispersaron en 5 ml de agua desmineralizada Después, se añadieron 30 g de perlas de zirconio (diámetro 0,5 mm).
Posteriormente, la suspensión se molió en un molino de rodillo con una velocidad fijada a 150 RPM. Después de ± 60 horas se obtuvo una nanosuspensión acuosa, dichas nanopartículas con un tamaño de partícula medio de 304 ± 42 nm. Además, la nanosuspensión fue estable después de la dilución durante al menos 12 horas, como se evidencia en la
20 parte B de este ejemplo.
B. Disponibilidad del sistema
Un volumen de la nanosuspensión obtenida en la parte A de este ejemplo, que corresponde con la dosis terapéutica de
25 flubendazol, se diluyó con agua potable en un reservorio de agua potable usada para los cerdos. Se tomaron muestras en el reservorio y en los pezones 0, 1, 2, 4, 6, 12 y 24 horas después de la adición de la suspensión al agua potable. La concentración de flubendazol en todas las muestras se determinó. La concentración de flubendazol en el reservorio de agua potable y los pezones sólo se redujo un 10% después de 12 horas. Después de 24 horas, la concentración de flubendazol disminuyó 15 y 45 % en el reservorio y los pezones, respectivamente.
30
Ejemplo 2: Formación del cocristal de flubendazol y ácido adípico
Más aun en este ejemplo, se repitió la preparación del ejemplo 1, rindiendo una nanosuspensión con nanopartículas que tienen un tamaño de partícula medio de 182 ± 4 nm.
35 La nanosuspensión se diluyó a la dosis terapéutica en el agua potable. Las muestras se tomaron inmediatamente después de la dilución y a las 2, 4, 6, 8, 10, 12 y 24 horas después de la dilución para medir el tamaño de partícula en función del tiempo. Un resumen de los resultados se da en la Tabla 2.
40 Tabla 2: Tamaño de la partícula en función del tiempo
45
50
55
- Intervalo de tiempo (h)
- Tamaño medio de partícula ± SD (nm)
- 0
- 182 ± 4
- 2
- 175 ± 5
- 4
- 190 ± 8
- 6
- 186 ± 5
- 8
- 193 ± 3
- 10
- 195 ± 2
- 12
- 199 ± 12
- 24
- 243 ± 8
Como se evidencia en la tabla 2, el tamaño medio de partícula de los nanocristales obtenidos permanece estable durante al menos 24 horas después de la dilución en el agua potable.
60
Ejemplo 3: Preparación de una nanosuspensión con ácido succínico y flubendazol
0,25 g flubendazol (antihelmíntico basado en bencimidazol), 0,4 g de ácido succínico (un ácido dicarboxílico) y 0,0625 g de Tween® 80 (un agente tensioactivo no iónico) se dispersa en 5 ml de agua desmineralizada. Después se añadieron 65 30 g de perlas de zirconio (diámetro 0,5 mm).
7
Claims (1)
-
imagen1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP11185803 | 2011-10-19 | ||
| EP11185803 | 2011-10-19 | ||
| PCT/EP2012/070617 WO2013057169A1 (en) | 2011-10-19 | 2012-10-18 | Pharmaceutical nanosuspension |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2548706T3 true ES2548706T3 (es) | 2015-10-20 |
Family
ID=47088845
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES12779018.6T Active ES2548706T3 (es) | 2011-10-19 | 2012-10-18 | Nanosuspensión farmacéutica |
Country Status (13)
| Country | Link |
|---|---|
| US (1) | US10251866B2 (es) |
| EP (1) | EP2768485B1 (es) |
| AU (1) | AU2012324911B2 (es) |
| BR (1) | BR112014009242A8 (es) |
| CA (1) | CA2852347C (es) |
| DK (1) | DK2768485T3 (es) |
| ES (1) | ES2548706T3 (es) |
| HR (1) | HRP20151004T1 (es) |
| HU (1) | HUE027923T2 (es) |
| PL (1) | PL2768485T3 (es) |
| SI (1) | SI2768485T1 (es) |
| TW (1) | TWI580442B (es) |
| WO (1) | WO2013057169A1 (es) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP6830058B2 (ja) * | 2015-03-02 | 2021-02-17 | 武田薬品工業株式会社 | ナノ共結晶を含有する懸濁液または組成物およびこれらの製造方法 |
| EP3170817A1 (en) * | 2015-11-20 | 2017-05-24 | Faes Farma, S.A. | Co-crystals of benzimidazole compounds |
| CN108403646B (zh) * | 2018-04-08 | 2021-04-20 | 新疆医科大学第一附属医院 | 阿苯达唑纳米微粉及其制备方法 |
| CN113318079B (zh) * | 2021-05-13 | 2024-01-09 | 江西博莱大药厂有限公司 | 一种提高三氯苯达唑颗粒溶出度的方法及其溶出度检测方法 |
| CN114224834B (zh) * | 2021-12-24 | 2022-11-11 | 沈阳伟嘉生物技术有限公司 | 一种具有较高生物利用度的阿苯达唑纳米混悬剂及其制备方法 |
| SI4389116T1 (sl) * | 2022-12-23 | 2025-12-31 | Dechra Ltd | Farmacevtska vodna flubendazol suspenzija |
| CN117462491B (zh) * | 2023-11-26 | 2024-08-27 | 江西省保灵动物保健品有限公司 | 一种阿苯达唑混悬液及其制备方法 |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5145684A (en) * | 1991-01-25 | 1992-09-08 | Sterling Drug Inc. | Surface modified drug nanoparticles |
| US5932544A (en) | 1994-05-31 | 1999-08-03 | Xoma Corporation | Bactericidal/permeability-increasing protein (BPI) compositions |
| ITMI20021074A1 (it) | 2002-05-20 | 2003-11-20 | Actimex S R L | Composizione ternaria comprendente una sostanza attiva e processo di comacinazione per la sua preparazione |
| CA2514733A1 (en) * | 2003-02-28 | 2004-09-16 | Transform Pharmaceuticals, Inc. | Pharmaceutical co-crystal compositions of drugs such as carbamazepine, celecoxib, olanzapine, itraconazole, topiramate, modafinil, 5-fluorouracil, hydrochlorothiazide, acetaminophen, aspirin, flurbiprofen, phenytoin and ibuprofen |
| WO2005118577A1 (en) * | 2004-04-22 | 2005-12-15 | Transform Pharmaceuticals, Inc. | Novel saperconazole crystalline forms and related processes, pharmaceutical compositions and methods |
| CA2621800A1 (en) | 2005-09-06 | 2007-03-15 | Astellas Pharma Inc. | Fine particles of poorly soluble drug having enteric base material adsorbed on the surface thereof |
| CN101568330A (zh) * | 2006-06-30 | 2009-10-28 | 伊休蒂卡有限公司 | 用于制备纳米粒形式的生物活性化合物的方法 |
| PL2118055T3 (pl) * | 2007-02-09 | 2014-01-31 | Zoetis Uk Ltd | Środki przeciwpasożytnicze |
| EP2167043A4 (en) * | 2007-06-06 | 2013-05-01 | Univ South Florida | NEW USE CO-CRYSTAL COMPOSITIONS |
| WO2010080754A2 (en) | 2009-01-06 | 2010-07-15 | Pharmanova, Inc. | Nanoparticle pharmaceutical formulations |
| WO2011036676A2 (en) | 2009-09-23 | 2011-03-31 | Ashwini Nangia | Stable cocrystals of temozolomide |
-
2012
- 2012-10-16 TW TW101138015A patent/TWI580442B/zh active
- 2012-10-18 HR HRP20151004TT patent/HRP20151004T1/hr unknown
- 2012-10-18 US US14/352,154 patent/US10251866B2/en active Active
- 2012-10-18 SI SI201230316T patent/SI2768485T1/sl unknown
- 2012-10-18 AU AU2012324911A patent/AU2012324911B2/en active Active
- 2012-10-18 HU HUE12779018A patent/HUE027923T2/en unknown
- 2012-10-18 BR BR112014009242A patent/BR112014009242A8/pt not_active Application Discontinuation
- 2012-10-18 CA CA2852347A patent/CA2852347C/en active Active
- 2012-10-18 DK DK12779018.6T patent/DK2768485T3/en active
- 2012-10-18 ES ES12779018.6T patent/ES2548706T3/es active Active
- 2012-10-18 EP EP12779018.6A patent/EP2768485B1/en active Active
- 2012-10-18 PL PL12779018T patent/PL2768485T3/pl unknown
- 2012-10-18 WO PCT/EP2012/070617 patent/WO2013057169A1/en not_active Ceased
Also Published As
| Publication number | Publication date |
|---|---|
| US10251866B2 (en) | 2019-04-09 |
| US20140255498A1 (en) | 2014-09-11 |
| TWI580442B (zh) | 2017-05-01 |
| WO2013057169A1 (en) | 2013-04-25 |
| HRP20151004T1 (hr) | 2015-11-20 |
| CA2852347C (en) | 2020-06-30 |
| SI2768485T1 (sl) | 2015-12-31 |
| DK2768485T3 (en) | 2015-10-05 |
| EP2768485A1 (en) | 2014-08-27 |
| TW201323013A (zh) | 2013-06-16 |
| AU2012324911B2 (en) | 2016-09-15 |
| PL2768485T3 (pl) | 2015-12-31 |
| CA2852347A1 (en) | 2013-04-25 |
| BR112014009242A2 (pt) | 2017-06-13 |
| AU2012324911A1 (en) | 2014-05-22 |
| EP2768485B1 (en) | 2015-07-22 |
| HUE027923T2 (en) | 2016-11-28 |
| BR112014009242A8 (pt) | 2017-06-20 |
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