Abstract
A novel approach for drug design based on the oral carbapenem analog tebipenem pivoxil (TP) has been proposed. The formation of the tebipenem pivoxil-β-cyclodextrin (TP-β-CD) complex resulted in changes concerning physicochemical properties of TP, which is significant for planning the development of an innovative pharmaceutical formulation as well as in the modifications of biological activity profile of the studied delivery system. The inclusion of TP into β-cyclodextrin (β-CD) was confirmed by spectral (infrared and Raman spectroscopies) and thermal method (differential scanning calorimetry). Precise indications of TP domains responsible for interaction with β-CD were possible through a theoretical approach. The most important physicochemical modifications obtained as an effect of TP inclusion were changes in solubility and its rate depending on acceptor fluids, and an increase in chemical stability in the solid state. Biologically essential effects of TP and β-CD interactions were decreased TP permeability through Caco–2 cell monolayers with the use of efflux effect inhibition and increased antibacterial activity. The proposed approach is an opportunity for development of the treatment in resistant bacterial infections, in which along with physicochemical modifications induced by a drug carrier impact, a carrier synergy with a pharmacological potential of an active pharmaceutical substance could be used.
Highlights
The carbapenems, which belong to the β-lactam antibiotics, are unique because of the broad spectrum of bacteriostatic activity due to the relative resistance to hydrolysis by most β-lactamases [1]
The work focused on preparing the tebipenem pivoxil (TP)-β-CD complex via a dry mixing technique [20]
In order to identify the tebipenem pivoxil-β-cyclodextrin (TP-β-CD) complex, spectroscopic (FT-IR and Raman spectra coupled with Density Functional Theory (DFT) calculations as supporting methods) and thermal (DSC) methods were used
Summary
The carbapenems, which belong to the β-lactam antibiotics, are unique because of the broad spectrum of bacteriostatic activity due to the relative resistance to hydrolysis by most β-lactamases [1]. Influence of inclusion into β-cyclodextrin on physicochemical and biological properties of tebipenem pivoxil and analysis, decision to publish, or preparation of the manuscript
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