Preliminary Preformulation Investigation of Tebufelone, A Novel Non-Steroidal Anti-Inflammatory Drug

Abstract

A preliminary preformulation investigation of tebufelone, a novel member of the di-tert-butyl phenol class of non-steroidal anti-inflammatory compounds was conducted. Radiolabeled tebufelone was found to be very poorly water soluble (∼1 μg/mL) with no significant pH effect upon solubility. It is considerably more soluble in both long and medium chain lipids and very soluble in polar solvents such as ethanol. The calculated apparent log P_{octanol/water} is approximately 5.5 Tebufelone has a melting point of 69°C and an enthalpy of fusion of 20 cal/g. No evidence of polymorphism was detected upon reheating or after precipitation from an ethanol solution. Dissolution of tebufelone in simulated intestinal fluid, USP (without pancreatin) with 2% bile salts (50% sodium cholate/50% sodium deoxycholate) failed to increase proportionally with calculated surface area at a mean particle size of 90 μm suggesting that the hydrophobicity of the drug precludes efficient wetting of the drug particle size is decreased to this level.