Preparation and evaluation of azithromycin binary solid dispersions using various polyethylene glycols for the improvement of the drug solubility and dissolution rate

Ehsan Adeli

doi:10.1590/s1984-82502016000100002

Abstract

ABSTRACT Azithromycin is a water-insoluble drug, with a very low bioavailability. In order to increase the solubility and dissolution rate, and consequently increase the bioavailability of poorly-soluble drugs (such as azithromycin), various techniques can be applied. One of such techniques is "solid dispersion". This technique is frequently used to improve the dissolution rate of poorly water-soluble compounds. Owing to its low solubility and dissolution rate, azithromycin does not have a suitable bioavailability. Therefore, the main purpose of this investigation was to increase the solubility and dissolution rate of azithromycin by preparing its solid dispersion, using different Polyethylene glycols (PEG). Preparations of solid dispersions and physical mixtures of azithromycin were made using PEG 4000, 6000, 8000, 12000 and 20000 in various ratios, based on the solvent evaporation method. From the studied drug release profile, it was discovered that the dissolution rate of the physical mixture, as the well as the solid dispersions, were higher than those of the drug alone. There was no chemical incompatibility between the drug and polymer from the observed Infrared (IR) spectra. Drug-polymer interactions were also investigated using Differential Scanning Calorimetry (DSC), Powder X-Ray Diffraction (PXRD) and Scanning Election Microscopy (SEM). In conclusion, the dissolution rate and solubility of azithromycin were found to improve significantly, using hydrophilic carriers, especially PEG 6000.

Highlights

Azithromycin (Figure 1) is a semi-synthetic antibiotic obtained from erythromycin
The calculated percentage of drug content for drug-Polyethylene glycols (PEG) 6000 was between the ranges of 97.50% to 99.62%, the drug content of the drug-PEG 4000SDs was in the range of 97.57% to 99.64%
The solvent evaporation approach was used for the preparation of Azithromycin solid dispersions

Summary

Introduction

Azithromycin (Figure 1) is a semi-synthetic antibiotic obtained from erythromycin. It is a Macrolide antibiotic. This drug is a nitrogen-containing macrolide (Azalide), with indications and usage similar to Erythromycin All macrolides, such as azithromycin inhibit RNA dependent protein synthesis by binding reversibly to the 50S ribosomal subunits of susceptible microorganisms (Patil et al, 2011; Montejo-Bernardo et al, 2005; Beckers et al, 1995; Champney, Burdine, 1998). Azithromycin can be used for prophylaxis, and act as a component of drug regimen in the treatment of Mycobacterium avium complex (MAC) infections It has activity against gram-positive organisms and offers an increased gram-negative coverage over erythromycin and clarithromycin (Moffat et al, 2011; Sweetman, 2009; Palanisamy, Khanam, 2011)

Methods

Results

Conclusion