Systems biology approach to study permeability of paracetamol and its solid dispersion

Sheraz Khan, Amr Elshaer, Ayesha S Rahman, Peter Hanson, Yvonne Perrie, Afzal-Ur-Rahman Mohammed

Research output: Contribution to journalArticle

Abstract

Physiological changes that take place at cellular level are usually reflective of their level of gene expression. Different formulation excipients have an impact on physiological behavior of the exposed cells and in turn affect transporter genes, enterocyte-mediated metabolism and toxicity biomarkers. The aim of this study was to prepare solid dispersion of paracetamol and evaluate genetic changes that occur in Caco-2 cell lines during the permeability of paracetamol alone and paracetamol solid dispersion formulations. Paracetamol-PEG 8000 solid dispersion was prepared by melt fusion method and the formulation was characterised using differential scanning calorimetry (DSC), scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR). Formulation of solid dispersion resulted in the conversion of crystalline drug into an amorphous form. Permeability studies showed that paracetamol absorption was higher from the solid dispersion formulation. DNA microarrays analysis was carried out in order to investigate the involvement of any efflux/uptake transporters in paracetamol or its solid dispersion permeability. Neither transporter carriers nor efflux proteins were found to be involved in the absorption of paracetamol or its PEG solid dispersion. Gene expression analysis established that paracetamol toxicity was potentially reduced upon formulation into solid dispersion when ATP binding cassette (ABC) and solute carrier transporter (SLC) genes were analyzed.
LanguageEnglish
Pages272-279
Number of pages8
JournalInternational Journal of Pharmaceutics
Volume417
Issue number1-2
Early online date25 Dec 2010
DOIs
Publication statusPublished - 30 Sep 2011

Fingerprint

Systems Biology
Acetaminophen
Permeability
Gene Expression
Caco-2 Cells
Enterocytes
Excipients
Differential Scanning Calorimetry
Fourier Transform Infrared Spectroscopy
Microarray Analysis
Oligonucleotide Array Sequence Analysis
Electron Scanning Microscopy
Genes
Adenosine Triphosphate
Biomarkers
Cell Line

Keywords

  • acetaminophen
  • caco-2 cells
  • differential scanning calorimetry
  • tumor cell line
  • pharmaceutical chemistry
  • excipients
  • humans
  • scanning microscopy
  • oligonucleotide array sequence analysis
  • permeability
  • polyethylene glycols
  • Fourier transform infrared spectroscopy
  • systems biology

Cite this

Khan, Sheraz ; Elshaer, Amr ; Rahman, Ayesha S ; Hanson, Peter ; Perrie, Yvonne ; Mohammed, Afzal-Ur-Rahman. / Systems biology approach to study permeability of paracetamol and its solid dispersion. In: International Journal of Pharmaceutics. 2011 ; Vol. 417, No. 1-2. pp. 272-279.
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Systems biology approach to study permeability of paracetamol and its solid dispersion. / Khan, Sheraz; Elshaer, Amr; Rahman, Ayesha S; Hanson, Peter; Perrie, Yvonne; Mohammed, Afzal-Ur-Rahman.

In: International Journal of Pharmaceutics, Vol. 417, No. 1-2, 30.09.2011, p. 272-279.

Research output: Contribution to journalArticle

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AU - Rahman, Ayesha S

AU - Hanson, Peter

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AU - Mohammed, Afzal-Ur-Rahman

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