Development of Co-amorphous Systems of Cefdinir by Using Spray Drying Technique: Preparation, Characterization, and In Vitro Evaluation

Abstract

Backgrond & Aim: The aim of the present study is to develop co-amorphous systems of cefdinir (a broad- spectrum antibiotic that belongs to the third generation of oral cephalosporins), in order to improve its dissolution rate, and subsequently its bioavailability, and to increase its physical stability.

Materials and Methods: Co-amorphous systems have been prepared using spray-drying technique starting from aqueous solutions by using different amino acids with various molar ratios.

Prepared co-amorphous systems were characterized for their solid state using Fourier- Transform Infrared Spectroscopy (FTIR), Scanning Electron Microscope (SEM), Differential Scanning Calorimetry (DSC), and X-ray Diffractometry (PXRD). The prepared systems have been evaluated for their drug release in media with different pH. Also, accelerated stability studies were carried out on the optimized co-amorphous system using various conditions of temperature and relative humidity (25⁰ C/ RH= 0%, 40⁰ C/ RH= 0%, and 40⁰ C/ RH= 75%).

Results: All the prepared systems showed a significant improvement in drug release at different pH compared with the pure crystalline drug, but the best performance was seen with arginine-based systems. SEM results showed a disappearance of the acicular shape of cefdinir particles in arginine-based systems only. DSC and PXRD results showed a transformation from the crystalline form of cefdinir into co-amorphous form only in the arginine-based systems. The optimized co-amorphous system was stable for at least 2 months under wet conditions, and remained stable for 6 months under dry conditions. The improved stability for this system was attributed to the intermolecular ionic interactions (salt formation) between the drug and arginine which were studied by FTIR analysis.

Conclusion: Co-amorphous systems technology using arginine as a co-former can be used as a promising method to improve the aqueous solubility of weakly acidic drugs such as cefdinir.