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  • Title: Spray dried nanospheres for inclusion complexes of cefpodoxime proxetil with β-cyclodextrin, 2-hydroxypropyl-β-cyclodextrin and methyl-β-cyclodextrin: improved dissolution and enhanced antibacterial activity.
    Author: Yurtdaş-Kırımlıoğlu G.
    Journal: Drug Dev Ind Pharm; 2021 Aug; 47(8):1261-1278. PubMed ID: 34606394.
    Abstract:
    OBJECTIVE: The aim of the current research was the development hard cellulose capsules containing cefpodoxime proxetil (CEF) (BCS-Class II) encapsulated nanospheres of inclusion complexes with β-CD, HP-β-CD and M-β-CD for efficient antibacterial therapy. SIGNIFICANCE: The reason for this phenomenon is to bring an innovative approach to effective oral antimicrobial therapy with hard cellulose capsules containing spray dried nanospheres of CEF with β-CD, HP-β-CD and M-β-CD by means of increased solubility, dissolution rate and improved antibacterial efficiency with lower oral dose. METHODS: Phase solubility analyses was performed to evaluate the drug/CD interaction, involving the stoichiometry and apparent stability constant. Following the preparation of inclusion complexes by spray-drying method, complexes were characterized for physical, solid-state and microbiological analyses. In vitro dissolution from hard cellulose capsules containing CEF and CEF/β-CD, CEF/HP-β-CD and CEF/M-β-CD complexes were performed. RESULTS: According to AL type phase solubility curves, complexes were formulated as 1:1 molar ratio. The solubility of pure CEF was determined as 0.241 ± 0.002 mg mL-1, the solubility of inclusion complexes increased solubility from 3 to 5 times. The strong host-guest interaction was confirmed for CEF/HP-β-CD and CEF/M-β-CD complexes with SEM, DSC, FT-IR and 1H-NMR analyses. Inclusion complexes were more efficient on bacterial cells (2-4 fold) than pure CEF both Staphylococcus aureus, Escherichia coli and Klebsiella pneumoniae. Hard-cellulose capsules filled with inclusion complexes exhibited significantly faster release than unprocessed CEF. CONCLUSION: Hard-cellulose capsules containing CEF/HP-β-CD and CEF/M-β-CD complexes appear to be superior alternative to commercially available CEF tablets for effective antibacterial therapy.
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