Use of amino acids as counterions improves the solubility of the BCS II model drug, indomethacin

Amr Elshaer, Sheraz Khan, Dhaya Perumal, Peter Hanson, Afzal-Ur-Rahman Mohammed

Research output: Contribution to journalArticle

Abstract

The number of new chemical entities (NCE) is increasing every day after the introduction of combinatorial chemistry and high throughput screening to the drug discovery cycle. One third of these new compounds have aqueous solubility less than 20µg/mL [1]. Therefore, a great deal of interest has been forwarded to the salt formation technique to overcome solubility limitations. This study aims to improve the drug solubility of a Biopharmaceutical Classification System class II (BCS II) model drug (Indomethacin; IND) using basic amino acids (L-arginine, L-lysine and L-histidine) as counterions. Three new salts were prepared using freeze drying method and characterised by FT-IR spectroscopy, proton nuclear magnetic resonance ((1)HNMR), Differential Scanning Calorimetry (DSC) and Thermogravimetric analysis (TGA). The effect of pH on IND solubility was also investigated using pH-solubility profile. Both arginine and lysine formed novel salts with IND, while histidine failed to dissociate the free acid and in turn no salt was formed. Arginine and lysine increased IND solubility by 10,000 and 2296 fold, respectively. An increase in dissolution rate was also observed for the novel salts. Since these new salts have improved IND solubility to that similar to BCS class I drugs, IND salts could be considered for possible waivers of bioequivalence.
LanguageEnglish
Pages363-372
Number of pages10
JournalCurrent Drug Delivery
Volume8
Issue number4
Publication statusPublished - Jul 2011

Fingerprint

Indomethacin
Solubility
Salts
Amino Acids
Pharmaceutical Preparations
Lysine
Arginine
Histidine
Basic Amino Acids
Therapeutic Equivalency
Freeze Drying
Differential Scanning Calorimetry
Drug Discovery
Magnetic Resonance Spectroscopy
Acids

Keywords

  • amino acids
  • biopharmaceutics
  • differential scanning calorimetry
  • pharmaceutical chemistry
  • hydrogen-ion concentration
  • indomethacin
  • magnetic resonance spectroscopy
  • solubility
  • Fourier transform infrared spectroscopy
  • tablets
  • therapeutic equivalency

Cite this

Elshaer, Amr ; Khan, Sheraz ; Perumal, Dhaya ; Hanson, Peter ; Mohammed, Afzal-Ur-Rahman. / Use of amino acids as counterions improves the solubility of the BCS II model drug, indomethacin. In: Current Drug Delivery. 2011 ; Vol. 8, No. 4. pp. 363-372.
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Use of amino acids as counterions improves the solubility of the BCS II model drug, indomethacin. / Elshaer, Amr; Khan, Sheraz; Perumal, Dhaya; Hanson, Peter; Mohammed, Afzal-Ur-Rahman.

In: Current Drug Delivery, Vol. 8, No. 4, 07.2011, p. 363-372.

Research output: Contribution to journalArticle

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