Application of Twin Screw Extrusion in the Manufacture of Cocrystals, Part I: Four Case Studies

Abstract

The application of twin screw extrusion (TSE) as a scalable and green process for the manufacture of cocrystals was investigated. Four model cocrystal forming systems, Caffeine-Oxalic acid, Nicotinamide-trans cinnamic acid, Carbamazepine-Saccharin, and Theophylline-Citric acid, were selected for the study. The parameters of the extrusion process that influenced cocrystal formation were examined. TSE was found to be an effective method to make cocrystals for all four systems studied. It was demonstrated that temperature and extent of mixing in the extruder were the primary process parameters that influenced extent of conversion to the cocrystal in neat TSE experiments. In addition to neat extrusion, liquid-assisted TSE was also demonstrated for the first time as a viable process for making cocrystals. Notably, the use of catalytic amount of benign solvents led to a lowering of processing temperatures required to form the cocrystal in the extruder. TSE should be considered as an efficient, scalable, and environmentally friendly process for the manufacture of cocrystals with little to no solvent requirements.

Synthesis and characterization of copper-caffeine complex for anti-bacterial studies using MIC method

“…5) is well aligned to the literature and fits for the same 11 . The major peaks (R1) located at 2θ values correspond to the characteristic of monoclinic phase of CuO (JCPDS NO80-1268) due to low concentration of caffeine in the complex.…”

“…The IR spectra of copper-caffeine complex show four major peaks (Fig.7).Absorption at 3458 cm -1 presence of amine group with slight moisture content and absorption at 1637 cm -1 shows ketone group. The band at 670 cm -1 (finger print region) indicates metal ion peak and absorption at 2360 cm -1 indicates C-N stretching frequency [10][11][12][13][14] . The IR spectrum obtained shows absorption at 3420 cm -1 indicates presence of amine group (Fig.…”

Recent Developments in Mechanochemical Materials Synthesis by Extrusion

“…A co-crystal is a crystalline structure made up of two or more components in a well-defined stoichiometric ratio, where each component may be either an atom, ion, or molecule. [53] Co-crystals of APIs are of significant interest to the pharmaceutical industry as they can lead to increased solubility and bioavailability, as well as enhanced physical stability and improved mechanical properties compared to pure APIs. [54] They are conventionally prepared by melt crystallization, sublimation, and solution crystallization.…”

Pharmaceutical Cocrystals: An Overview

“…Grinding methods are of two types: neat grinding and solvent drop grinding [85,86] . Some newly emerging methods used for the formation of cocrystals are ultrasound assisted solution method [87,88] , supercritical fluid atomization technique [46,89] , spray drying technique [90,91] , hot melt extrusion technique [92,93] .…”

“…The limitations of this method include both coformer and API should be miscible in molten form and not used for thermolabile drugs [29,92,93] .…”