University of Limerick
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Amorphization versus cocrystallization of celecoxib-tramadol hydrochloride using CO2-assisted nano-spray drying

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journal contribution
posted on 2023-08-03, 07:31 authored by Aaron O'SullivanAaron O'Sullivan, Kevin M. RyanKevin M. Ryan, Luis PadrelaLuis Padrela

The manipulation of both solid-state form and particle size is a versatile means by which physicochemical properties of pharmaceutical drugs may be improved/fine-tuned. The work presented herein describes the solid-state and particle size control of the most recently FDA-approved pharmaceutical cocrystal, composed of two APIs, Celecoxib-Tramadol hydrochloride (Seglentis®), using a continuous atomization technique, namely supercritical CO2-assisted nano-spray drying. Using a three-factorial design of experiments, both (co)amorphous and cocrystalline samples were generated, depending on processing conditions. Mean particle sizes ranged from 120 nm to 1160 nm, with solution flow rate showing the most significant effect due to its impact on atomized droplet sizes. While all (co)amorphous samples displayed a similar morphology, one set of conditions produced a (co)amorphous sample with a larger degree of intermolecular interactions, comparable with the hydrogen bonding network observed in the cocrystalline samples. Tabletting of four formulations was carried out to investigate the impact of particle size and solid-state on tabletability, compactability and compressibility. While all formulations performed adequately in these critical quality attributes, the formulations which contained cocrystalline particles underperformed regarding tabletability and compactability due to their irregular shape and larger size. However, due to the increased prevalence of intermolecular interactions, the cocrystalline and (co)amorphous samples with a larger degree of hydrogen bonding led to improved compressibility.


Synthesis and Solid State Pharmaceutical Centre (SSPC)

Science Foundation Ireland

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Journal of CO2 Utilization 73, 102529



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