The Influence of Excipients on the Physicochemical and Biological Properties of a Bactericidal, Labile Ester Prodrug in a Salt Form – A Case Study of Cefetamet Pivoxil Hydrochloride

  • Jakub Dzitko University of Medical Sciences, Swiecickiego
  • Przemyslaw Zalewski University of Medical Sciences, Swiecickiego
  • Daria Szymanowska University of Life Sciences, Wojska Polskiego
  • Piotr Garbacki University of Medical Sciences
  • Magdalena Paczkowska University of Medical Sciences, Swiecickiego
  • Judyta Cielecka Piontek University of Medical Sciences, Swiecickiego
Keywords: Cefetamet Pivoxyl, pharmaceutical formulations, bactericidal activity, drug carriers

Abstract

The article presents an innovative approach to a bactericidal drug design based on a cephem prodrug analogue – cefetamet pivoxil hydrochloride. The emergence of cefetamet pivoxil hydrochloride excipient systems (mannitol, hydroxypropyl methyl cellulose, pregelatinised starch, lactose monohydrate, magnesium stearate, polyvinylpyrrolidone) caused changes in the physicochemical properties of cefetamet pivoxil hydrochloride. They are significant for planning the development of an innovative pharmaceutical formulation. The biological activity profile of the prodrug was also modified. FTIR spectra were used to study interactions between cefetamet pivoxil hydrochloride and the excipients. The theoretical approach to the analysis of experimental spectra enabled precise indication of cefetamet pivoxil hydrochloride domains responsible for interaction with the excipients. The interactions between cefetamet pivoxil hydrochloride and the excipients resulted in some  important physicochemical modifications: acceptor fluid-dependent changes in solubility and the dissolving rate as well as a decrease in the chemical stability of cefetamet pivoxil hydrochloride in the solid state, especially during thermolysis. The interactions between cefetamet pivoxil hydrochloride and the excipients also had biologically essential effects. There were changes in its permeability through artificial biological membranes simulating the gastrointestinal tract, which depended on the pH value of the acceptor solution. Cefetamet pivoxil hydrochloride combined with the excipient systems exhibited greater bactericidal potential against Staphylococcus aureus. Its bactericidal potential against Enterococcus faecalis, Pseudomonas aeruginosa and Proteus mirabilis doubled. The new approach provides an opportunity to develop treatment of resistant bacterial infections. It will enable synergy between the excipient and the pharmacological potential of an active pharmaceutical substance with modified physicochemical properties induced by the drug carrier.

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Author Biographies

Jakub Dzitko, University of Medical Sciences, Swiecickiego

Department of Pharmacognosy, Pozna? University of Medical Sciences, Swiecickiego 4, 60-781 Poznan, Poland

Przemyslaw Zalewski, University of Medical Sciences, Swiecickiego

Department of Pharmacognosy, Pozna University of Medical Sciences, Swiecickiego 4, 60-781 Poznan, Poland

Daria Szymanowska, University of Life Sciences, Wojska Polskiego

Department of Biotechnology and Food Microbiology, Pozna University of Life Sciences, Wojska Polskiego 48, 60-627 Pozna?, Poland

Piotr Garbacki, University of Medical Sciences

Department of Pharmacognosy, Pozna? University of Medical Sciences

Magdalena Paczkowska, University of Medical Sciences, Swiecickiego

Department of Pharmacognosy, Pozna University of Medical Sciences, Swiecickiego 4, 60-781 Poznan, Poland

Judyta Cielecka Piontek, University of Medical Sciences, Swiecickiego

Department of Pharmacognosy, Pozna University of Medical Sciences, Swiecickiego 4, 60-781 Poznan, Poland

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Published
2018-08-23
How to Cite
Dzitko, J., Zalewski, P., Szymanowska, D., Garbacki, P., Paczkowska, M., & Piontek, J. (2018). The Influence of Excipients on the Physicochemical and Biological Properties of a Bactericidal, Labile Ester Prodrug in a Salt Form – A Case Study of Cefetamet Pivoxil Hydrochloride. JOURNAL OF ADVANCES IN CHEMISTRY, 15(2), 6218-6234. https://doi.org/10.24297/jac.v15i2.7560
Section
Articles