Mechanistic Evaluation of the Effect of Sintering on Compritol® 888 ATO Matrices

Abstract

The present research studied the effect of sintering technique in the development of a controlled release formulation for ketorolac tromethamine. The method consisted of mixing drug and wax powder (Compritol 888 ATO) along with lactose as diluent and talc as lubricant followed by direct compression at room temperature. The compressed fluffy matrices were kept at 80 degrees C for 1, 2, and 3 h for sintering. The sintered tablets were characterized by their physical parameters and in vitro dissolution profile. The sintering time markedly affected the drug release properties of Compritol 888 ATO matrices. It is notable that the release rate of ketorolac tromethamine from matrices was inversely related to the time of sintering. This may be due to the increase in the extent and firmness of sintering which further compacts the mass so that drug release is affected. Contact angle measurement and scanning electron microscopy analysis indicated that heat treatment caused the wax to melt and redistribute. This redistributed wax formed a network-like structure in which the drug along with lactose is entrapped. This particular formed matrix is responsible for retarding the drug release. Fourier transform infrared spectroscopy results did not show any drug-wax interaction due to sintering. Differential scanning calorimetric and powder X-ray diffraction studies ruled out the occurrence of solid solution and polymorphic changes of the drug. Drug release from the wax tablets with or without sintering was best described by the Higuchi equation.