Mechanoradical-induced degradation in a pharmaceutical blend during high-shear processing

Pharmaceutical Development and Technology
Mark A PolizziJoshua Colvin

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.

References

Jan 1, 1997·Journal of Pharmaceutical Sciences·B C Hancock, G Zografi
Feb 21, 2002·Pharmaceutical Development and Technology·Kenneth C WatermanChristopher J Roberts
Jul 13, 2002·Journal of Pharmaceutical Sciences·Harry G Brittain
Aug 12, 2005·Chemical Reviews·Martin K Beyer, Hauke Clausen-Schaumann
Apr 25, 2007·Journal of Pharmaceutical Sciences·Peter L D WildfongSteven M Short

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