Coated pelletized dosage form: Effect of compaction on drug release

Abstract

The goal of this study was to investigate the effect of compaction of a coated pelletized dosage form on drug release. Three sizes of microcrystalline cellulose and hydrous lactose pellets containing 4% chlorpheniramine maleate (CPM) were manufactured using a rotogranulator (Glatt GPCG-1). Pellets having mesh cuts of: 590–840 μm (20/30 mesh); 420–590 μm (30/40 mesh); and 250–420 μm (40/60 mesh) were then coated with an aqueous ethylcellulose pseudolatex dispersion plasticized with 24% dibutyl sebacate (DBS). Percent weight gains were 25, 30 and 35% for the 20/30, 30/40 and 40/60 mesh pellets, respectively. Coated pellets were blended with 39.3% by weight excipients, then mixtures lubricated and compacted using a Korsch PH106 instrumented rotary press set at 5 kN and 20 rpm (0.30 s contact time). Magnesium stearate was used as the lubricant at a 0.7% level. Excipients used were microcrystalline cellulose, spray dried lactose, pregelatinized starch, dicalcium phosphate, spray dried sorbitol, polyethylene glycol 8000 powder and compressible sugar. Results indicated this coating to be suitable for the controlled release of CPM from small pellets (250–840 μm). However, films did not have the appropriate mechanical properties to withstand compaction stress without rupturing, regardless of the pellets particle size and excipients used. After compaction, depending on pellet size, between 65–100% CPM was released after one hour as opposed to 10–30% for the non-compacted material. The controlled release properties of the pellets were therefore lost during the process.