Mechanical Properties Improvement of Dexibuprofen through Dexibuprofen-Caffeine Co-crystal Formation by Ultrasound assisted Solution Co-crystallization Method

Abstract

The ability of an active pharmaceutical ingredient to be compressed is directly affected by its mechanical properties, such as flowability and tabletability. Dexibuprofen (DXI) with poor mechanical properties has improved its flowability and tabletability by co-crystal formation with caffeine (CAF) using ultrasound assisted co-crystallization (USSC) method in chloroform solvent. The characterization of the co-crystal formation included crystal morphology, powder X-ray diffractogram, and thermal behavior. The mechanical properties testing including flowability (compressibility index) and tabletability (tensile strength and elastic recovery) were conducted on DXI-CAF co-crystal and pure DXI. The tabletability test was conducted at 10 to 60 kg/cm2 of compression force. The characterization results show that the USSC result has a unique crystal habit, diffractogram, melting point that is different from pure DXI, and this indicates the formation of DXI-CAF co-crystal. The DXI-CAF co-crystal compressibility index was in the good category, while pure DXI was in the poor category. The maximum tensile strength value of the DXI-CAF co-crystal was 1.526 MPa achieved at a compression force of 50 kg/cm2, whilst the maximum tensile strength value of pure DXI was only 0.853 MPa achieved at a compression force of 20 kg/cm2. The elastic recovery curve showed the percentage of elastic recovery of DXI-CAF co-crystal was better than pure DXI. It can be concluded that the co-crystal formation of DXI-CAF by the USSC method was able to improve the mechanical properties (flowability and tabletability) of dexibuprofen.Keywords: dexibuprofen, caffeine, ultrasound assisted co-crystallization, tensile strength, elastic recovery