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Trimethoprim-Based multicomponent solid Systems: Mechanochemical Screening, characterization and antibacterial

Giusi Piccirillo1, Rafael Aroso1, João A Baptista1

  • 1University of Coimbra, Coimbra Chemistry Centre, Department of Chemistry, Rua Larga, 3004-535, Coimbra, Portugal.

International Journal of Pharmaceutics
|July 4, 2024
PubMed
Summary
This summary is machine-generated.

Mechanochemistry created novel trimethoprim solid systems. These systems enhanced trimethoprim

Keywords:
Antibacterial activityDissolution rateE. coliMechanochemistryS. aureusTrimethoprim

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Area of Science:

  • Pharmaceutical Sciences
  • Solid-State Chemistry
  • Medicinal Chemistry

Background:

  • Trimethoprim (TMP) is a vital antibiotic with limitations in solubility and activity.
  • Developing new formulations can improve drug efficacy and patient outcomes.
  • Mechanochemistry offers a solvent-free approach for creating advanced pharmaceutical solids.

Purpose of the Study:

  • To develop multicomponent solid systems of trimethoprim (TMP) using mechanochemistry.
  • To enhance TMP's aqueous solubility, dissolution rate, and antibacterial activity through coformer selection.
  • To identify novel salt and eutectic mixtures of TMP with improved pharmaceutical properties.

Main Methods:

  • Mechanochemical synthesis of binary and equimolar systems using GRAS coformers and other APIs.
  • Characterization using thermal analysis, powder X-ray diffraction (PXRD), and Fourier-transform infrared spectroscopy (FTIR).
  • Assessment of intrinsic dissolution rate and antibacterial activity against Gram-positive and Gram-negative bacteria.

Main Results:

  • Identified 3 equimolar systems as salts and 4 as eutectic mixtures.
  • Achieved a 25% increase in TMP dissolution rate with nicotinic acid (salt) and 5% with paracetamol (eutectic).
  • Observed enhanced antibacterial activity for several TMP-coformer systems, notably against E. coli with curcumin and ciprofloxacin.

Conclusions:

  • Mechanochemically prepared multicomponent TMP systems offer improved dissolution rates and enhanced antibacterial efficacy.
  • Coformer selection is crucial for optimizing TMP's pharmaceutical and antimicrobial properties.
  • These findings present a promising alternative to conventional trimethoprim formulations.