Comparative study between pH, time and colonic bacterial enzyme triggered polymers for colonic delivery of coated ketoprofen multi-particulates.

Background: In this study, we aimed to prepare, evaluate, and compare drug-loaded pellets of ketoprofen coated with different triggering mechanisms for colonic delivery.

Objective: The purpose of this study was to compare Eudragit S100 and Eudragit L100 based pH-dependent, hydroxypropyl cellulose and ethyl cellulose-based time-dependent and high methoxylated pectin and ethyl cellulose-based colonic bacterial enzymatic degradation-dependent coatings over drug-loaded pellets for most efficient colon targeting.

Methods: Any possible drug-polymer interactions were analyzed using Fourier-transform infrared spectroscopy and differential scanning calorimetry. Drug-loaded pellets were prepared using powder layering technology. Different batches of coated pellets were prepared for in vitro evaluation, and optimized batches were selected. These optimized batches were investigated for surface topography by scanning electron microscopy and for colon targeting efficiency by in vivo X-ray roentgenography and gamma scintigraphy studies in white New Zealand rabbits.

Results: The drug and polymers were found to be compatible. The prepared coated multi-particulates exhibited favorable micrometric properties. In vitro dissolution studies showed that the polysaccharide pectin high methoxylated and ethyl cellulose-coated optimized batch limited drug release to 16.724 ± 1.124% in the upper gastrointestinal tract and released up to 91.556 ± 3.144% in the colon following zero-order Korsmeyer-peppas super case-II transport (mean dissolution time 36.1779 h). Scanning electron microscopy analysis confirmed the surface characteristics of the pellets before and after dissolution. In vivo studies in New Zealand white rabbits using X-ray roentgenography and gamma scintigraphy demonstrated the optimized batch's gastrointestinal transit and colon targeting efficiency.

Conclusion: Statistically, the polysaccharide-based formulation showed promising results for targeted drug release in the colon.