Alteration of crystallinity and thermal properties from incompatibility between ibuprofen and boundary lubricants

Abstract

Lubricant is an essential compound for pharmaceutical formulation since it is often required to ensure the success of pharmaceutical manufacturing especially tablet compression and capsule filling process. Most lubricants used in pharmaceutical industry are boundary lubricants. The most commonly used boundary lubricants are metallic salts of fatty acids such as magnesium stearate and stearic acid. However, other lubricants, including fatty acid esters, inorganic materials and polymers have been used in the cases when stearic acid and metallic salts of fatty acids do not meet the performance expectation. In this study, stearic acid, magnesium stearate, aluminium monostearate and glyceryl dibehenate were chosen as the boundary lubricants whereas ibuprofen (IBU) was employed as the model drug. The aims of this study are to investigate the incompatibility between IBU and these boundary lubricants and to observe the alteration of crystallinity and thermal properties with differential scanning calorimetry (DSC), hot stage microscopy (HSM) and powder X-ray diffraction (PXRD) techniques. The eutectic formation between IBU and all boundary lubricants was revealed with DSC, PXRD and HSM techniques. The thermal properties of individual substance and all physical mixture (PM) between IBU and lubricants from DSC analysis were confirmed with the HSM technique. The partial melting temperature (PMT) and complete melting temperature (CMT) observed from HSM were close to the thermal parameters obtained from DSC results. Moreover, FT-IR spectra indicated an interaction between IBU and boundary lubricants via hydrogen bonding since the vibrational frequency in the region 1700–1400 cm−1 shifted to lower value. This understanding of alteration of crystallinity and thermal properties from incompatibility between compounds is beneficial for pharmaceutical solid dosage form development.