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Preparation and characterization of amino acids-based trimethoprim salts

Amr Elshaer1, Peter Hanson, Tony Worthington

  • 1Aston Pharmacy School, Aston University, Aston Triangle, Birmingham B4 7ET, UK. a.u.r.mohammed@aston.ac.uk.

Pharmaceutics
|December 5, 2013
PubMed

Insights

Novel trimethoprim (TMP) salts with amino acids significantly improved solubility and antibacterial activity. These findings could lead to faster-acting antibiotics with potentially lower therapeutic doses.

Area of Science:

  • Pharmaceutical Chemistry
  • Microbiology
  • Drug Delivery

Background:

  • Trimethoprim (TMP) is a dihydrofolate reductase (DHFR) inhibitor crucial for bacterial death.
  • Poor oral bioavailability of TMP is attributed to its low solubility and permeability.
  • Developing strategies to enhance TMP's physicochemical properties is essential for improved therapeutic efficacy.

Purpose of the Study:

  • To prepare novel salts of trimethoprim (TMP) using anionic amino acids (aspartic and glutamic acid) as counterions.
  • To enhance the solubility and dissolution rate of TMP.
  • To evaluate the impact of salt formation on TMP's antibacterial activity.

Main Methods:

  • Salt preparation via lyophilisation.
  • Characterization using FT-IR spectroscopy, 1HNMR, DSC, and TGA.
  • Assessment of microbiological activity against TMP-sensitive Escherichia coli.

Main Results:

  • Successful formation of TMP salts with aspartic and glutamic acid in a 1:1 molar ratio.
  • Achieved a remarkable 280-fold improvement in TMP solubility.
  • The novel salts retained antibacterial activity and demonstrated a larger zone of inhibition compared to native TMP.

Conclusions:

  • Amino acid salt formation significantly enhances TMP's solubility and dissolution.
  • The new TMP salts exhibit potent antibacterial activity, potentially offering faster onset and reduced dosage.
  • Further research into ion-pairing effects on drug permeability is warranted.

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