Development and In Vitro Evaluation of Ketoprofen Extended Release Pellets Using Powder Layering Technique in a Rotary Centrifugal Granulator

Abstract

Powder layering technique was evaluated using laboratory scale centrifugal granulator instrument to prepare extended release pellet dosage form of ketoprofen. Ethyl cellulose and shellac polymers were used for drug layering and extended release coating in the same apparatus. Inert sugar spheres were intermittently treated with drug powder and binding solution. Combination of ethyl cellulose (45cps) and shellac was evaluated as binders at different levels (1:3 ratio, at 6%, 12%, 16% and 21%w/w polymer) for drug loading and for extended release coating (1:3 ratio at 2%, 4% and 7% w/w polymer). Pellets were evaluated for drug release study using paddle apparatus in pH 6.8 Phosphate buffer, 900ml at 100 rpm. Ethyl cellulose and shellac when used as binder during drug layering did not extend the ketoprofen release beyond 4h. However, coating of drug loaded pellets using ethyl cellulose and shellac resulted in extended release profile of ketoprofen for about 10h. Ethyl cellulose coating alone at a level of 3% w/w resulted in extended release profile. Coated pellets were evaluated for sphericity, Hardness-Friability Index and scanning electron microscopy. Scanning electron micrographs of the pellets showed a uniform coating of polymer on the core pellets substantiating the use of centrifugal granulator for extended release coating. Release pattern from the optimized batch was best explained by Higuchi's model. The drug release pattern from the pellets was found to be Non-Fickian anomalous type, involving both diffusion and erosion mechanism. Accelerated stability study of the coated pellets filled in hard gelatin capsule was conducted for 3-month period and observed for the effect on drug release profile.

Multiscale Shellac-Based Delivery Systems: From Macro- to Nanoscale

“…Notably, the introduction of additives, such as HPMC, into single-layer shellac-based coatings is another simple and efficient method of adjusting their performance . Pellets coated with ethyl cellulose and shellac could greatly prolong the release time of ketoprofen, compared with pellets using ethyl cellulose and shellac as a binder. , Shellac containing tartaric acid has been used as a plasticizer to coat ascorbic acid-loaded pellets; the release of ascorbic acid was controlled by the size and number of pores in the coating . As shown in Figure A, water-soluble polysaccharide HPMC incorporated in the shellac coating could improve the resistance of a dietary colonic delivery system, as demonstrated by the coated-acylated pectin bead with a drug release rate of <5% in simulated gastric juice .…”