Rapid Development of an Accelerated In Vitro Release Method for a Novel Antibiotic-Eluting Biologic Envelope

Introduction:A novel antibiotic-eluting biologic envelope has been developed to secure implantable devices, such as cardiac implantable electronic devices (CIEDs), while minimizing infection risk through the extended release of rifampin and minocycline.This envelope leverages the regenerative properties of an intact extracellular matrix to support tissue integration and healing.To advance clinical applications, product development, and manufacturing processes, a rapid and reliable method for assessing in vitro elution of antibiotics from the biologic envelope is essential.Methods: A rabbit subcutaneous dorsal implant model was used to evaluate in vivo drug elution.Initial in vitro studies identified optimal parameters for a final accelerated in vitro elution method.Tested conditions included dissolution media volume, pH, temperature, agitation speed, and surfactant additions.An accelerated elution method was optimized based on the tested parameters.Results: In vivo studies demonstrated rapid, immediate elution followed by gradual elution over 14 days, reaching at least 85% of total antibiotic content.Based on exploratory studies testing various parameters, an accelerated in vitro elution method was developed.This accelerated method produced 90% elution of both minocycline and rifampin by the final timepoints (6 and 30 hours, respectively), with minimal variability (relative standard deviation < 10%).Model fitting suggested that the in vitro method mimics the in vivo elution kinetics of the biologic envelope, with a strong linear correlation between dissolution methods for rifampin and minocycline.Conclusion: This study demonstrated the feasibility of a rapid process to develop an accelerated in vitro elution method.The accelerated in vitro method was validated and demonstrated a strong correlation with the in vivo elution kinetics of both antibiotics.