Effect of process and formulation variables on formation of diclofenac sodium pellets prepared by melt technique

Abstract

A melt pelletization process was investigated in a planetary mixer with heat from heating jacket. The effect of process variables, i.e. mixing speed (100 rpm and 200 rpm), temperature (58°C and 78°C) and time (5 min and 15 min), and formulation variable, i.e. types of filler (lactose and dibasic calcium phosphate), on formation of diclofenac sodium pellets, were investigated by mean of factorially designed experiments using glyceryl monostearate as a binder. The effect of binder melting point and viscosity was also investigated through the formulation containing lactose and glyceryl monostearate, Precirol® AT05, Compritol 888 ATO®, Gelucire 50/02 or Tristearin®. The amounts of binder required to form pellets were dependent on types of binders and fillers. Mixing speed and types of filler were the most important variables affecting the physical properties of pellets. Increased mixing speed produced larger pellets with narrow size distribution. Pellets with dibasic calcium phosphate were smoother and rounder than pellets with lactose. True density of pellets depended on true density of filler. The binder of lower melting point gave rounder pellets. The binder of lower viscosity produced narrow size distribution of pellets. All the pellets possessed good flowability. Drug content of pellets prepared with lactose complied with USP 27 and the pellets were stable after storage at 45°C and 75% relative humidity for 4 mouths. Drug degradation could occur in pellets prepared with dibasic calcium phosphate. However, diclofenac related compound A was not presented. The 80 % drug release was obtained for most formulations. The results obtained from this study proved that the process and formulation variables affecting quality of pellets prepared by planetary mixer.