Development and characterization of lyophilized cefpodoxime proxetil-Pluronic^® F127/polyvinylpyrrolidone K30 solid dispersions with improved dissolution and enhanced antibacterial activity

Abstract

The aim of this study was the development of hard-cellulose capsules containing cefpodoxime proxetil (CEF) (BCS Class II) loaded novel Pluronic^® F127 (P127)/Polyvinylpyrrolidone K30 (PVP) solid dispersions (SDs) using ultrasonic probe induced solvent-lyophilization method for effective antibacterial treatment by means of improved saturated aqueous solubility, dissolution rate, reduced particle size, and wettability. SDs were evaluated for physical and solid-state analyses. The solubility of pure CEF was calculated as 0.269 ± 0.005 mg/mL, SDs formulated with P127/PVP exhibited increased solubility from 3.5- to 8-fold. Molecular distribution of CEF in SDs and formation of CEF loaded amorphous polymeric network were confirmed with morphological study, thermal analysis, Fourier-transform infrared spectroscopy (FT-IR), and ¹H-NMR studies. Staphylococcus aureus (ATCC 29213), Escherichia coli (ATCC 25922), and Klebsiella pneumoniae (ATCC 700603) were used to investigate the antibacterial effectiveness of the SDs. The minimum inhibitory concentration (MIC) values of the P127/PVP SDs were found 2–8 times lower than the pure CEF. All SDs from hard-cellulose capsules exhibited significantly faster release than unprocessed CEF. The profiles of SDs and reference were detected to be dissimilar according to difference (f₁) and similarity factor (f₂). Hard-cellulose capsules containing CEF loaded P127/PVP SDs appear to be feasible alternative to commercially available CEF tablets for effective antibacterial therapy at lowest dose.

Graphical Abstract

Keywords:

• Cefpodoxime proxetil
• Pluronic^® F127
• polyvinylpyrrolidone
• solid dispersion
• dissolution rate
• antibacterial activity

Acknowledgements

The authors thank Neutec Pharma (İstanbul, Turkey) for supplying a gift sample of Cefpodoxime proxetil and antibacterial activity studies and Exp.Chem. Serkan Levent for his assistance in FT-IR and ¹H-NMR analyses.

Disclosure statement

The authors declare no potential conflicts of interest to disclose the current research.