Purpose: First used as a pain killer, Aspirin also brings lesser known benefits that can be essential to prevent cardiovascular events. Further applications are also currently being developed to prevent certain forms of cancer as well as cognitive declines. Results obtained in this survey confirmed the potential of using hot melt extrusion as an enabling technology for such applications while smoothening some of Aspirin well known secondary effects for the digestive system. Aspirin formulation is very well documented but has not really been changed for decades. So we decided to investigate the possible improvement in bioavailability in order to foster both its known usages and its repurposing for cancer or cardio vascular applications. A recent survey done in Brazil with a similar model drug confirmed extrusion as a technology that can bring important benefits by obtaining formulations with improved characteristics, such as faster disintegration, higher drug solubilization, and better stability. In the case of Aspirin, extrusion could therefore help to smoothen some of its well-known secondary effects for the digestive system. In our survey we used control parameters on Rondol vertical extruder such as drug loading, screw configuration and process temperature to demonstrate that at 45% AcetylSalicylic Acid (ASA) – 55% water soluble polymer Soluplus® extruded at 130°C, the Aspirin is completely amorphous with no tendency to recrystallize after 6 weeks. Methods: All trials were done while using 2 ASA Novacyl grades varying only in particle size. ASA grades show endothermic melting peaks at 147.7 and 150.6°C for ASA 2020 and 2080 respectively. Pre-weighed powder formulation blends of BASF Soluplus® and ASA were mixed and two parameters, drug loading (20, 30 and 50% w/w) and HME barrel temperature (120 and 130°C) were varied to investigate their effect on the physical form. Extrusions were carried out at RONDOL using a 10mm co-rotating twin-screw ‘All in One’ Vertical (L/D 40:1, feed rate of 35 rpm). Results: The XRD patterns for 20 and 30% w/w ASA 2020-loaded Soluplus® blends respectively at temperatures ranging from 40 to 150°C demonstrate that above 120°C the ASA is completely amorphous and thus dissolved in the Soluplus®, which has a glass transition temperature (Tg) of 70°C. DSC analysis of the 20 and 30% w/w ASA-loaded pellets manufactured by HME at 120°C shows that the endothermic melting peaks at 147.7 and 150.6°C for 7 ASA in all samples has disappeared. This is due to the ASA being in its amorphous form within the Soluplus® polymer. XRD analysis of the 30% w/w ASA-loaded pellets produced diffraction patterns with a smooth halo pattern and no diffraction peaks associated with ASA. This would further suggest that the ASA is dispersed at the molecular level and its crystallinity completely removed. This is not surprising as the pellets were manufactured at 120°C and the XRD data demonstrated that at this temperature the ASA dissolves in the molten Soluplus®. Furthermore, the mixing and shear of the extruder screws adds further heat and energy to the extrudate, consequently melting the ASA into its amorphous form and mixing it into the Soluplus®. The subsequent cooling causes the Soluplus® to solidify holding the ASA in its amorphous form. XRD diffraction patterns for the 50% w/w ASA-loaded pellets indicates low-intensity diffraction peaks at 5, 15 and 23 2Thếta, similar to the ASA control. This demonstrates that the ASA within the 50% w/w ASA-loaded pellets has lost some of its crystalline content as a result of some ASA being dissolved within the Soluplus®, However, the Soluplus® does not have enough solvation energy to dissolve all of the ASA. Based on this data it is estimated that 45% w/w ASA in Soluplus® should result in solid dispersions that contain completely amorphous ASA. Finally XRD diffraction patterns for the 30% w/w ASA-loaded Soluplus® extruded pellets 6 weeks after manufacture show no diffraction peaks belonging to ASA and demonstrate that it is still in its amorphous form 6 weeks after manufacture. Conclusion: In vitro pharmacokinetic studies would now need to be performed to validate the impact of ASA amorphization and understand the interaction between ASA and Soluplus® and its impact on bioavailability and release profile. References: 1. https://www.seqens.com/en/white-paper-on-aspirin-1st-result-of-the-technology-cooperation-between-seqens-and-rondol-announced-in-march/ 2. Victoire de Margerie & Hans Maier “From Pharma Adapted Extrusion to brand new pharma fitted extrusion design” in Practical Guide to Hot Melt extrusion — Mohammed Maniruzzaman, Smither Rapra, 2015
