(233t) Continuous Manufacturing of Co-Crystals in Twin Screw Extruder: A Case Study

Co-crystals are crystalline materials, comprised of two or more components that are solids at room temperature and held together by noncovalent forces. A pharmaceutical co-crystal consists of an active pharmaceutical ingredient and a pharmaceutically acceptable co-former. Nowadays, pharmaceutical co-crystals are becoming an integral part in pharmaceutical strategies as they can improve the physicochemical properties of the API.Wet granulation is a widely used process in the pharmaceutical industry and its main goal is to produce granules from fine particles of active pharmaceutical ingredients (API) and excipients using a granulation liquid. In a twin screw extruder, the process is undergone under the high shear forces exerted by the screws on the particles.

The main aim of this study is to investigate and develop novel processes for continuous pharmaceutical processing of co-crystals. Wet granulation was chosen as a manufacturing method since it combined synthesis and granulation in a single continuous operation step. A 12 mm twin screw extruder (Three-Tec, Switzerland) with a length-to-diameter ratio of 40 was used for the manufacturing of the granules.A novel Theophylline-Aspirin (THP-ASP) model system was selected for the study. The effects of different process parameters (feed rate, screw speed, liquid-to-solid ratio) and formulation parameters (API and co-former ratio) on the final granules properties and the extent of conversion were investigated. Particle size distribution was analysed using Microtrac particle size analyser. The solid state form of the final granules was characterised with various techniques, including DSC, and PXRD.