Evidence map›Paper›PMID 40649731›Full record

ArticleInternational journal of molecular sciences2025

Development of a Cyclodextrin-Based Drug Delivery System to Improve the Physicochemical Properties of Ceftobiprole as a Model Antibiotic.

Dariusz Boczar, Wojciech Bocian, Jerzy Sitkowski, Karolina Pioruńska, Katarzyna Michalska

Abstract read
In one paragraph

Article in International journal of molecular sciences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors.

Dariusz BoczarDepartment of Synthetic Drugs, National Medicines Institute, Chełmska 30/34, 00-725 Warsaw, Poland.ORCID 0000-0002-1881-7356
Wojciech BocianLaboratory for Analysis of Bioactive Compounds, Institute of Organic Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, 01-224 Warsaw, Poland.ORCID 0000-0003-3862-8656
Jerzy SitkowskiFalsified Medicines and Medical Devices Department, National Medicines Institute, Chełmska 30/34, 00-725 Warsaw, Poland.ORCID 0000-0002-9962-6024
Karolina PioruńskaFalsified Medicines and Medical Devices Department, National Medicines Institute, Chełmska 30/34, 00-725 Warsaw, Poland.ORCID 0000-0002-4720-0494
Katarzyna MichalskaDepartment of Synthetic Drugs, National Medicines Institute, Chełmska 30/34, 00-725 Warsaw, Poland.ORCID 0000-0002-7329-3081

Funding

Ministry of Science and Higher Education 1/2024, 1/2025
6 · The paper itself

Abstract

This study presents a methodology for developing a cyclodextrin-based delivery system for ceftobiprole, a poorly water-soluble and amphoteric drug, chemically stable in acidic conditions. Ceftobiprole is a broad-spectrum cephalosporin antibiotic administered clinically as its water-soluble prodrug, ceftobiprole medocaril, due to limited aqueous solubility of the parent compound. Solubility enhancement was achieved through complexation with anionic sulfobutylether-β-cyclodextrin (SBE-β-CD). At a pH below 3, ceftobiprole is protonated and cationic, which facilitates electrostatic interactions with the anionic cyclodextrin. An optimised high-performance liquid chromatography (HPLC) method was used to assess solubility, the impurity profile, and long-term chemical stability. X-ray powder diffraction (XRPD) confirmed the amorphous nature of the system and the absence of recrystallization. Nuclear magnetic resonance (NMR) and attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy supported the formation of a host-guest complex. The freeze-dried system prepared from 0.1 M formic acid solution contained negligible residual acid due to nearly complete sublimation. The most promising formulation was a ternary system of ceftobiprole, maleic acid, and SBE-β-CD (1:25:4 molar ratio), showing ~300-fold solubility improvement, low levels of degradation products, and stability after eight months at -20 °C. After pH adjustment to a parenterally acceptable level, the formulation demonstrated solubility and a pH comparable to the marketed drug product.

Indexed as

Anti-Bacterial Agentsbeta-CyclodextrinsCephalosporinsCyclodextrinsDrug Delivery SystemsDrug StabilityHydrogen-Ion ConcentrationSolubilitySpectroscopy, Fourier Transform InfraredX-Ray DiffractionAnti-Bacterial Agentsbeta-CyclodextrinsceftobiproleCephalosporinsCyclodextrinsSBE4-beta-cyclodextrinceftobiprolecyclodextrindrug deliverylyophilisationSBE-β-CDternary system

Identifiers

PMID40649731
PMCPMC12249915

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.