Process Safety Evaluation Using Non-Isothermal Calorimetry
Billy Edwards, Pharmaceutical Process Development/Pilot Plant, Roche Carolina Inc., 6173 Old Marion Highway, Florence, SC 29501, Thimma Rawalpally, Chemical Development, Roche Carolina Inc., 6173 Old Marion Highway, Florence, SC 29501 and Joshua Allen, Pilot Plant, Roche Carolina Inc., 6173 Old Marion Highway, Florence, SC 29501

Exothermic reactions occuring during temperature changes are common issues in process safety, however they are often difficult to characterize. A method of evaluating exothermic reactions in non-isothermal systems is presented and applied to two reactions: a Suzuki cross-coupling and the decomposition of a lithiated intermediate that is believed to form a benzyne on heating.

In evaluation of the Suzuki cross-coupling, the information gathered is used to model the reaction scaled up for full scale manufacturing and to specify a safe heating profile near the boiling point of the reaction mixture. The decomposition of benzyne-producing lithiated species is characterized for several substrates and our attempts to lessen the thermal hazards are discussed.

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Case Studies in Pharmaceutical and Biopharmaceutical Development

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