We developed alginate-based floating microbeads of clarithromycin with therapeutic oils for the possible eradication of Helicobacter pylori (H. pylori) infections by enhancing the residence time of the carrier at the site of infection. In pursuit of this endeavor, the alginate was blended with hydroxy propyl methyl cellulose (HPMC) as an interpenetrating polymer to develop beads by ionotropic gelation using calcium carbonate as a gas generating agent. The developed microbeads remained buoyant under gastric conditions for 24 h. These microbeads initially swelled and afterwards decreased in size, possibly due to the erosion of the polymer. Furthermore, swelling was also affected by the type of encapsulated oil, i.e., swelling decreased with increasing concentrations of eucalyptus oil and increased with increasing concentrations of oleic acid. Antibacterial assays of the formulations showed significant antibacterial activity against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli); these assays also showed synergistic activity between clarithromycin and therapeutic oils as evident from the higher zone of inhibition of the microbeads as compared to the pure drug and oils. Scanning electron microscopy (SEM) images revealed a smoother surface for oleic acid containing the formulation as compared to eucalyptus oil containing the formulation. Differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) revealed the development of a stable formulation, while Fourier transform infrared spectrophotometry (FTIR) studies did not reveal any interaction between the polymers and the active ingredients. Optimized formulations (CLM3 and CLM6) were designed to release the drug in a controlled manner in gastric media by Fickian diffusion. Conclusively, the developed microbeads are a promising carrier to overcome the narrow therapeutic index and low bioavailability of clarithromycin, while the presence of therapeutic oils will produce synergistic effects with the drug to eradicate infection effectively.
Keywords: clarithromycin; eucalyptus oil; floating microbeads; oleic acid; sodium alginate.