WO2014090889A1 - Solutions à usage oral comprenant de l'acide folique - Google Patents

Solutions à usage oral comprenant de l'acide folique Download PDF

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Publication number
WO2014090889A1
WO2014090889A1 PCT/EP2013/076255 EP2013076255W WO2014090889A1 WO 2014090889 A1 WO2014090889 A1 WO 2014090889A1 EP 2013076255 W EP2013076255 W EP 2013076255W WO 2014090889 A1 WO2014090889 A1 WO 2014090889A1
Authority
WO
WIPO (PCT)
Prior art keywords
folic acid
solution
oral
solutions
propylene glycol
Prior art date
Application number
PCT/EP2013/076255
Other languages
English (en)
Inventor
Angelos Karatzas
Original Assignee
Lamda Laboratories S.A.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Lamda Laboratories S.A. filed Critical Lamda Laboratories S.A.
Priority to EP13821079.4A priority Critical patent/EP2903596A1/fr
Publication of WO2014090889A1 publication Critical patent/WO2014090889A1/fr

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
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • 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
    • A61K9/08—Solutions
    • 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
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • 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

Definitions

  • the commercially available pharmaceutical aqueous Lexpec® 2.5mg/5ml Oral Solution which is marketed in the United Kingdom by Rosemont Laboratories Inc., contains 0.5 mg/ml folic acid.
  • this product also comprises as excipients mannitol, glycerin, disodium edetate, methyl-p- hydroxybenzoic acid, propyl-p-hydroxybenzoic acid, ethyl-p-hydroxybenzoic acid, dihydrogen phosphate sodium, disodium phosphate, strawberry flavour (containing propylene glycol) and water.
  • the quantitative composition of the product was approached by a set of laboratory studies, including inter alia a study of the rheological behavior of the solution for assessing the concentration of mannitol and glycerol, a pH measurement for assessing the concentration of phosphates and organoleptic tests for the assessment of the concentration of the flavouring agent.
  • This approach resulted in the following concentration values for the excipients of the product Lexpec ® 2.5mg/5ml Oral Solution: approximately 100 mg/ml for mannitol, about 200 mg/ml for glycerin, about 2.5 mg/ml for sodium dihydrogen phosphate, about 2.5 mg/ml for disodium phosphate and about 5 mg/ml for the strawberry flavour (which contains propylene glycol).
  • the concentration of folic acid in the solutions of the present invention is up to 30 mg/ml.
  • the concentration of folic acid is from 5 mg/ml to 25 mg/ml.
  • Natural sweetening agents that can be used in the present invention comprise mannitol, maltitol, sorbitol and mixtures thereof.
  • flavouring agents may comprise any of the many non-toxic natural or artificial flavouring agents known in the daily practice.
  • the flavouring agents used may comprise one or more of a variety of natural or artificial fruit flavours.
  • the flavouring agents may comprise one or more of natural or artificial vanilla, chocolate, and caramel flavourings, amongst others.
  • the present invention also provides stable folic acid solutions at concentrations much higher than those of the corresponding prior art solutions.
  • the volume is adjusted to the desired batch volume by adding water.
  • the pH of the solution is adjusted, if needed, to the range of 7.5 to 9.5 by adding sodium hydroxide solution.
  • Table 4 Compositions with increasing concentration of folic acid
  • Table 5 shows preferred oral solution compositions according to the present invention.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Nutrition Science (AREA)
  • Physiology (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Non-Alcoholic Beverages (AREA)

Abstract

L'invention porte sur des solutions à usage oral comprenant de l'acide folique en tant que principe actif et un véhicule liquide comprenant du propylèneglycol, du glycérol et de l'eau. Le pH de la solution est réglé dans la plage de 7,5 à 9,5. Les solutions de la présente invention présentent une excellente stabilité même sans la présence d'autres agents antimicrobiens et/ou antioxydants, en plus du propylèneglycol et du glycérol.
PCT/EP2013/076255 2012-12-12 2013-12-11 Solutions à usage oral comprenant de l'acide folique WO2014090889A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EP13821079.4A EP2903596A1 (fr) 2012-12-12 2013-12-11 Solutions à usage oral comprenant de l'acide folique

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GR20120100628A GR1008101B (el) 2012-12-12 2012-12-12 Ποσιμα διαλυματα φυλλικου οξεος
GR20120100628 2012-12-12

Publications (1)

Publication Number Publication Date
WO2014090889A1 true WO2014090889A1 (fr) 2014-06-19

Family

ID=49956130

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2013/076255 WO2014090889A1 (fr) 2012-12-12 2013-12-11 Solutions à usage oral comprenant de l'acide folique

Country Status (3)

Country Link
EP (1) EP2903596A1 (fr)
GR (1) GR1008101B (fr)
WO (1) WO2014090889A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2020221592A1 (fr) * 2019-05-01 2020-11-05 Unilever N.V. Composition de fortifiant

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115959944B (zh) * 2023-01-13 2024-02-13 天津市汉邦植物保护剂有限责任公司 植酸钙悬浮肥及其制备方法

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20090232943A1 (en) * 2008-03-12 2009-09-17 Aly Gamay Stabilized vitamin solutions; use thereof; process for their production; and formulations comprising the same

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20090232943A1 (en) * 2008-03-12 2009-09-17 Aly Gamay Stabilized vitamin solutions; use thereof; process for their production; and formulations comprising the same

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
ALFRED R BIAMONTE ET AL: "A Study of Folic Acid Stability in Solutions of the B Complex Vitamins*J", JOURNAL OF THE AMERICAN PHARMACEUTICAL ASSOCIATION, 31 January 1951 (1951-01-31), pages 313 - 320, XP055104247, Retrieved from the Internet <URL:http://onlinelibrary.wiley.com/store/10.1002/jps.3030400704/asset/3030400704_ftp.pdf?v=1&t=hs37bfs4&s=5123e2f45d7ba08a3e582afaa3e8feddbb650f44> [retrieved on 20140225] *
M VIGNESH ET AL: "Stabilization of folic acid in liquid dosage form: Formulation development, method validation and comparative analysis", INTERNATIONAL JOURNAL OF PHARMACEUTICAL AND CHEMICAL SCIENCES, 31 March 2012 (2012-03-31), pages 332 - 338, XP055104243, Retrieved from the Internet <URL:http://ijpcsonline.com/files/39.pdf> [retrieved on 20140225] *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2020221592A1 (fr) * 2019-05-01 2020-11-05 Unilever N.V. Composition de fortifiant

Also Published As

Publication number Publication date
GR1008101B (el) 2014-02-04
EP2903596A1 (fr) 2015-08-12

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