Bioassay-guided optimization of lipid-based erythromycin microparticles

Purpose: To optimize erythromycin microparticles by in vitro bioassay methods based on its antibacterial activity. Methods: The microparticles were produced by high shear homogenization. The effects of different lipid-to-surfactant ratios were studied. The hydrodynamic size of the different batches was evaluated using dynamic light scattering while bioactive drug load per batch was assessed in agar using bioassay methods. The antimicrobial activities of selected batches were tested ex vivo by determination of reduction in bacteraemia following administration of the microparticles to infected animals. Results: All batches had particles with hydrodynamic sizes < 8.5 microns. Batch 7 with a 2: 5: 2.5 (drug: surfactant: stearic acid) ratio, represents the optimized batch with a hydrodynamic size of 2281 nm, a bioactive drug loading capacity (BLC) of 4.67 ± 0.70 % and bioactive drug entrapment efficiency (BEE) of 10.51 %. The “microparticle MIC” against Staphylococcus aureus was 1.74 x 10-3 μg/ml. Despite containing lower amounts of erythromycin than the pure sample, the microparticles achieved comparable reduction in bacteraemia, with the optimized batch exhibiting lower variation in bacteraemia than the pure drug. Conclusion: Erythromycin microparticles have been successfully optimized with the aid of bioassay methods which has the advantage that only the bioactive drug concentration is factored in. This method eliminates problems posed by inadequate or non-discriminating chemical assay methods. Keywords: Microparticles, Erythromycin, Gastrointestinal, Bioavailability Antimicrobial, Bioactivity, Encapsulation