Telescoped approach to aryl hydroxymethylation in the synthesis of a key pharmaceutical intermediate.

An efficient synthetic approach leading to introduction of the hydroxymethyl group to an aryl moiety via combination of the Bouveault formylation and hydride reduction has been optimized using a rational, mechanistic-based approach. This approach enabled telescoping of the two steps into a single efficient process, readily amenable to scaleup.

Optimization of LY545694 tosylate controlled release tablets through pharmacoscintigraphy.

Purpose: To optimize a controlled release (CR) matrix formulation with two goals: (1) effectively deliver a prodrug to a preferred absorption region of the upper GI tract, and (2) afford a PK profile similar to a "reference" CR formulation.

Methods: A pharmacoscintigraphic clinical study was conducted using a flexible formulation design space. A six-arm, three-prototype study was employed to cover the formulation design space and assess performance against the reference formulation.

Strategies for the investigation and control of process-related impurities in drug substances.

The understanding, identification, quantification and control of impurities in drug substances are essential as new molecular entities are evaluated in clinical development. As chemical processes used to produce drug substances mature from the early phases of development through registration, a concomitant maturing of process-related impurity understanding and control is required. This paper outlines strategies available to pharmaceutical scientists to aid in that understanding.