Influence of operational variables in multi-particulate delayed release systems for colon-targeted drug delivery of celecoxib using extrusion spheronization

Abstract

The present research was aimed to formulate and evaluate pH and time-dependent multiparticulate systems for colon-targeted drug delivery of celecoxib (CXB) with maximum drug absorption, reduced peak plasma fluctuations, and minimum potential side effects. Multiple unit delayed release systems of the drug in MCC (Avicel^® PH-102) grade were prepared using polymethacrylate polymers (Eudragit^® L-100 and RSPO) as a granulating binder by the extrusion-spheronization technique and characterized for their shape, size, size distribution, friability, density, and moisture content. In vitro release studies were performed in 0.1N HCl, for first 2 h then further performed in phosphate buffer (pH 6.8) for 24 h. The resulting pellets were prepared by extrusion spheronization using different grades of polymethacrylate polymers as a granulating binder, showing a substantial decrease in drug release in initial 5 h (16.28-16.7%) and releasing most of the drug in 12-24 h. The geometric and arithmetic mean diameter ranged from (490 to 780 ΅m) and (636 to 734 μm), respectively. The minimum to maximum range for circularity, elongation and rectangle were found to be (0.847±0.009 to 0.965±0.078), (1.036±0.057 to 1.185±0.023), and (0.724±0.041 to 0.791±0.047) respectively showing the proper shape and size of the pellets. The content of CXB in the prepared pellets was observed between 98.70 and 99.47% justifying the uniform drug distribution. The in vitro dissolution studies showed that the retardant effect in initial 5 h and most of the drug release in 24 h depended on the ratio and concentration of different grades of methacrylate polymers used in the formulation. CXB-loaded MUPS prepared by the extrusion-spheronization technique using polymethacrylate polymers showed immense potential for colon-specific drug delivery of the drug.