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Published on: April 19, 2018
Mechanoradical-induced degradation in a pharmaceutical blend during high-shear processing
Mark A Polizzi1, Dharmendra Singhal, Joshua Colvin
1Pfizer Global Research and Development, Groton, Connecticut 06340, USA. mark.polizzi@pfizer.com
Abstract:
Mechanically generated radicals were shown to affect short-term stability of a model pharmaceutical formulation during high-shear processing. A formulation containing an oxidatively sensitive drug, either amorphous or crystalline, and a polymeric excipient was high-shear mixed and the resulting short-term degradation was determined with HPLC. High-shear mixing of the excipients was also carried out before drug addition to isolate effects on excipients versus those directly on the drug. Short-term drug stability was found to be strongly dependent on the amount of shear added to excipients prior to drug addition, regardless of morphology. A mechanism for the observed degradation based on mechanically generated radicals from microcrystalline cellulose is proposed. These results indicate that excipient high-shear exposure needs to be considered in regards to drug stability.
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