Improved pharmaceutical stability of a boronphenylalanine mannitol formulation for boron neutron capture therapy

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Abstract

Boron neutron capture therapy (BNCT) is a radiotherapy based cancer treatment requiring the availability of a low energy thermal neutron beam and a boron containing drug.These requirements limit BNCT availability with the latter pharmaceutical issue related to the extremely short shelf-life and clinical acceptability of the current fructose based L-boronpheylalanine (BPA) formulation.Resolution of the formulation issues would remove this factor and therefore the stability of an alternative mannitol BPA formulation has been investigated. A mannitol BPA solution formulation was prepared and either lyophilised or stored as a solution at varying temperatures. After suitable periods the formulation was analysed by HPLC for BPA and degradation products. Lyophilised and solution mannitol BPA formulations exhibited a temperature and time dependent loss of BPA with concomitant increases in degradation products. Autoclaving the solution induced and accelerated degradation. A solution or lyophilised mannitol BPA formulation has a shelf-life of between one and four years respectively, a marked improvement over the current fructose formulation.Due to temperature dependent degradation the formulation cannot be terminally sterilised by autoclaving.The enhanced stability of the mannitol formulation removes the requirement for extemporaneous aseptic preparation of BPA just prior to treatment and eliminates one of the issues complicating the delivery of BNCT.
LanguageEnglish
Pages735-739
Number of pages5
JournalEuropean Journal of Pharmaceutical Sciences
Volume48
Early online date23 Jan 2013
DOIs
Publication statusPublished - 2013

Fingerprint

Boron Neutron Capture Therapy
Mannitol
Pharmaceutical Preparations
Fructose
Temperature
Boron
Neutrons
Radiotherapy
Hot Temperature
High Pressure Liquid Chromatography
Therapeutics
Neoplasms

Keywords

  • boronphenylalanine
  • boron neutron capture therapy
  • formulation
  • stability
  • mannitol
  • fructose
  • pharmaceutical stability
  • boronphenyl alanine mannitol form

Cite this

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title = "Improved pharmaceutical stability of a boronphenylalanine mannitol formulation for boron neutron capture therapy",
abstract = "Boron neutron capture therapy (BNCT) is a radiotherapy based cancer treatment requiring the availability of a low energy thermal neutron beam and a boron containing drug.These requirements limit BNCT availability with the latter pharmaceutical issue related to the extremely short shelf-life and clinical acceptability of the current fructose based L-boronpheylalanine (BPA) formulation.Resolution of the formulation issues would remove this factor and therefore the stability of an alternative mannitol BPA formulation has been investigated. A mannitol BPA solution formulation was prepared and either lyophilised or stored as a solution at varying temperatures. After suitable periods the formulation was analysed by HPLC for BPA and degradation products. Lyophilised and solution mannitol BPA formulations exhibited a temperature and time dependent loss of BPA with concomitant increases in degradation products. Autoclaving the solution induced and accelerated degradation. A solution or lyophilised mannitol BPA formulation has a shelf-life of between one and four years respectively, a marked improvement over the current fructose formulation.Due to temperature dependent degradation the formulation cannot be terminally sterilised by autoclaving.The enhanced stability of the mannitol formulation removes the requirement for extemporaneous aseptic preparation of BPA just prior to treatment and eliminates one of the issues complicating the delivery of BNCT.",
keywords = "boronphenylalanine, boron neutron capture therapy, formulation, stability, mannitol, fructose, pharmaceutical stability, boronphenyl alanine mannitol form",
author = "Gavin Halbert and Moira Elliott and Steven Ford and Lindsay Dick and Elke Schmidt",
year = "2013",
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language = "English",
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AU - Schmidt, Elke

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AB - Boron neutron capture therapy (BNCT) is a radiotherapy based cancer treatment requiring the availability of a low energy thermal neutron beam and a boron containing drug.These requirements limit BNCT availability with the latter pharmaceutical issue related to the extremely short shelf-life and clinical acceptability of the current fructose based L-boronpheylalanine (BPA) formulation.Resolution of the formulation issues would remove this factor and therefore the stability of an alternative mannitol BPA formulation has been investigated. A mannitol BPA solution formulation was prepared and either lyophilised or stored as a solution at varying temperatures. After suitable periods the formulation was analysed by HPLC for BPA and degradation products. Lyophilised and solution mannitol BPA formulations exhibited a temperature and time dependent loss of BPA with concomitant increases in degradation products. Autoclaving the solution induced and accelerated degradation. A solution or lyophilised mannitol BPA formulation has a shelf-life of between one and four years respectively, a marked improvement over the current fructose formulation.Due to temperature dependent degradation the formulation cannot be terminally sterilised by autoclaving.The enhanced stability of the mannitol formulation removes the requirement for extemporaneous aseptic preparation of BPA just prior to treatment and eliminates one of the issues complicating the delivery of BNCT.

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