Abstract
Formation of different micro- to nanosized cocrystals of theophylline is addressed by using the supercritical enhanced atomization (SEA) process. The experimental results presented here help to highlight how to prepare cocrystals of theophylline (TPL) using a supercritical fluid-based technique to accomplish the required physicochemical properties of that active pharmaceutical ingredient (API). The SEA process shows a strong versatility and feasibility towards the formation of highly pure theophylline cocrystals, using tetrahydrofuran as a solvent. The formation of TPL cocrystals with different types of morphology and dissolution behaviour/properties is induced by using different coformers, such as urea, saccharin, gentisic acid, salicylic acid, glutaric acid, sorbic acid, 1-hydroxy-2-naphthoic acid, oxalic acid, maleic acid and nicotinamide. The solubility of each coformer in the dissolution medium of phosphate-buffered saline (pH 7.4 at 25°C) could determine the dissolving rate behaviour of the produced cocrystals. Consequently, the low-soluble coformers generate TPL cocrystals with a slow-dissolving rate, while the use of highly soluble coformers produces faster-dissolving TPL cocrystals. Albeit the SEA process operating temperature influences the mean cocrystal particle size, this technique shows a high potential as an effective cocrystal screening tool.
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