Preparation and characterisation of amino acids based trimethoprim salts

Amr ElShaer, Peter Hanson, Tony Worthington, Peter Lambert, Afzal R. Mohammed

Research output: Contribution to journalArticle

Abstract

Trimethoprim (TMP) is a dihydrofolate reductase (DHFR) inhibitor which prevents the conversion of dihydrofolic acid into tetrahydrofolic acid, resulting in the depletion of the latter and leading to bacterial death. Oral bioavailability of TMP is hindered by both its low solubility and low permeability. This study aims to prepare novel salts of TMP using anionic amino acids; aspartic and glutamic acid as counter ions in order to improve solubility and dissolution. TMP salts were prepared by lyophilisation and characterized using FT-IR spectroscopy, proton nuclear magnetic resonance (1HNMR), Differential Scanning Calorimetry (DSC) and Thermogravimetric analysis (TGA). Both the amino acids formed salts with TMP in a 1:1 molar ratio and showed a 280 fold improvement in solubility. Investigation of the microbiological activity of the prepared salts against TMP sensitive Escherichia coli showed that the new salts not only retained antibacterial activity but also exhibited higher zone of inhibition which was attributed to improved physicochemical characters such as higher solubility and dissolution. The results are an important finding that could potentially impact on faster onset of antibacterial activity and reduced therapeutic dose when administered to patients. Studies are underway investigating the effect of ion-pairing TMP with amino acids on the permeability profile of the drug.

LanguageEnglish
Article number4
Pages179-196
Number of pages17
JournalPharmaceutics
Volume4
Issue number1
DOIs
Publication statusPublished - 16 Feb 2012

Fingerprint

Trimethoprim
Salts
Amino Acids
Solubility
Permeability
Ions
Folic Acid Antagonists
Freeze Drying
Differential Scanning Calorimetry
Biological Availability
Glutamic Acid
Magnetic Resonance Spectroscopy
Escherichia coli
Acids
Pharmaceutical Preparations

Bibliographical note

© 2012 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).

Keywords

  • trimethoprim
  • salt formation
  • fourier transform infrared
  • 1H nuclear magnetic resonance
  • thermogrametric analysis
  • Pseudomonas aeruginosa
  • minimum inhibitory concentration studies

Cite this

@article{7082464087ea47688215702bc04e58ad,
title = "Preparation and characterisation of amino acids based trimethoprim salts",
abstract = "Trimethoprim (TMP) is a dihydrofolate reductase (DHFR) inhibitor which prevents the conversion of dihydrofolic acid into tetrahydrofolic acid, resulting in the depletion of the latter and leading to bacterial death. Oral bioavailability of TMP is hindered by both its low solubility and low permeability. This study aims to prepare novel salts of TMP using anionic amino acids; aspartic and glutamic acid as counter ions in order to improve solubility and dissolution. TMP salts were prepared by lyophilisation and characterized using FT-IR spectroscopy, proton nuclear magnetic resonance (1HNMR), Differential Scanning Calorimetry (DSC) and Thermogravimetric analysis (TGA). Both the amino acids formed salts with TMP in a 1:1 molar ratio and showed a 280 fold improvement in solubility. Investigation of the microbiological activity of the prepared salts against TMP sensitive Escherichia coli showed that the new salts not only retained antibacterial activity but also exhibited higher zone of inhibition which was attributed to improved physicochemical characters such as higher solubility and dissolution. The results are an important finding that could potentially impact on faster onset of antibacterial activity and reduced therapeutic dose when administered to patients. Studies are underway investigating the effect of ion-pairing TMP with amino acids on the permeability profile of the drug.",
keywords = "trimethoprim, salt formation, fourier transform infrared, 1H nuclear magnetic resonance, thermogrametric analysis, Pseudomonas aeruginosa, minimum inhibitory concentration studies",
author = "Amr ElShaer and Peter Hanson and Tony Worthington and Peter Lambert and Mohammed, {Afzal R.}",
note = "{\circledC} 2012 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).",
year = "2012",
month = "2",
day = "16",
doi = "10.3390/pharmaceutics4010179",
language = "English",
volume = "4",
pages = "179--196",
journal = "Pharmaceutics",
issn = "1999-4923",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "1",

}

Preparation and characterisation of amino acids based trimethoprim salts. / ElShaer, Amr; Hanson, Peter; Worthington, Tony; Lambert, Peter; Mohammed, Afzal R.

In: Pharmaceutics, Vol. 4, No. 1, 4, 16.02.2012, p. 179-196.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Preparation and characterisation of amino acids based trimethoprim salts

AU - ElShaer, Amr

AU - Hanson, Peter

AU - Worthington, Tony

AU - Lambert, Peter

AU - Mohammed, Afzal R.

N1 - © 2012 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).

PY - 2012/2/16

Y1 - 2012/2/16

N2 - Trimethoprim (TMP) is a dihydrofolate reductase (DHFR) inhibitor which prevents the conversion of dihydrofolic acid into tetrahydrofolic acid, resulting in the depletion of the latter and leading to bacterial death. Oral bioavailability of TMP is hindered by both its low solubility and low permeability. This study aims to prepare novel salts of TMP using anionic amino acids; aspartic and glutamic acid as counter ions in order to improve solubility and dissolution. TMP salts were prepared by lyophilisation and characterized using FT-IR spectroscopy, proton nuclear magnetic resonance (1HNMR), Differential Scanning Calorimetry (DSC) and Thermogravimetric analysis (TGA). Both the amino acids formed salts with TMP in a 1:1 molar ratio and showed a 280 fold improvement in solubility. Investigation of the microbiological activity of the prepared salts against TMP sensitive Escherichia coli showed that the new salts not only retained antibacterial activity but also exhibited higher zone of inhibition which was attributed to improved physicochemical characters such as higher solubility and dissolution. The results are an important finding that could potentially impact on faster onset of antibacterial activity and reduced therapeutic dose when administered to patients. Studies are underway investigating the effect of ion-pairing TMP with amino acids on the permeability profile of the drug.

AB - Trimethoprim (TMP) is a dihydrofolate reductase (DHFR) inhibitor which prevents the conversion of dihydrofolic acid into tetrahydrofolic acid, resulting in the depletion of the latter and leading to bacterial death. Oral bioavailability of TMP is hindered by both its low solubility and low permeability. This study aims to prepare novel salts of TMP using anionic amino acids; aspartic and glutamic acid as counter ions in order to improve solubility and dissolution. TMP salts were prepared by lyophilisation and characterized using FT-IR spectroscopy, proton nuclear magnetic resonance (1HNMR), Differential Scanning Calorimetry (DSC) and Thermogravimetric analysis (TGA). Both the amino acids formed salts with TMP in a 1:1 molar ratio and showed a 280 fold improvement in solubility. Investigation of the microbiological activity of the prepared salts against TMP sensitive Escherichia coli showed that the new salts not only retained antibacterial activity but also exhibited higher zone of inhibition which was attributed to improved physicochemical characters such as higher solubility and dissolution. The results are an important finding that could potentially impact on faster onset of antibacterial activity and reduced therapeutic dose when administered to patients. Studies are underway investigating the effect of ion-pairing TMP with amino acids on the permeability profile of the drug.

KW - trimethoprim

KW - salt formation

KW - fourier transform infrared

KW - 1H nuclear magnetic resonance

KW - thermogrametric analysis

KW - Pseudomonas aeruginosa

KW - minimum inhibitory concentration studies

UR - http://www.scopus.com/inward/record.url?scp=84858813306&partnerID=8YFLogxK

U2 - 10.3390/pharmaceutics4010179

DO - 10.3390/pharmaceutics4010179

M3 - Article

VL - 4

SP - 179

EP - 196

JO - Pharmaceutics

T2 - Pharmaceutics

JF - Pharmaceutics

SN - 1999-4923

IS - 1

M1 - 4

ER -