Cefuroxime axetil solid dispersion with polyglycolized glycerides for improved stability and bioavailability

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery Systems
• Prodrug Formulation

Background:

• Cefuroxime axetil (CA) is a broad-spectrum cephalosporin prodrug with poor aqueous solubility and variable oral bioavailability due to enzymatic hydrolysis before absorption.
• Developing stable amorphous solid dispersions is crucial for enhancing the solubility and therapeutic efficacy of poorly soluble drugs like CA.

Purpose of the Study:

• To formulate stable amorphous solid dispersions of cefuroxime axetil (CA) using hydrophilic carriers.
• To enhance the solubility, dissolution, and bioavailability of CA.
• To improve the stability of CA against enzymatic degradation.

Main Methods:

• Amorphous solid dispersions of CA were prepared using spray drying with Gelucire 50/13 (SDCAGA) and polyvinyl pyrrolidone (SDCAP).
• Characterization involved differential scanning calorimetry, X-ray powder diffraction, scanning electron microscopy, and Fourier transform infrared spectroscopy.
• Solubility, dissolution, and in vivo bioavailability in rats were evaluated.

Main Results:

• Both SDCAP and SDCAGA exhibited enhanced solubility and dissolution compared to amorphous CA (ACA) and crystalline CA, attributed to amorphization and solid dispersion formation.
• SDCAGA demonstrated superior bioavailability in rats compared to SDCAP, ACA, and CA.
• Physical stability was improved in solid dispersions due to hydrogen bonding interactions with carriers.

Conclusions:

• Amorphous solid dispersions, particularly with Gelucire 50/13, significantly enhance the oral bioavailability of cefuroxime axetil.
• Gelucire's lipolytic activity may protect the prodrug from premature enzymatic hydrolysis, contributing to improved in vivo performance.
• Hydrogen bonding interactions play a key role in stabilizing the amorphous solid dispersions.