An automated workstation for forced degradation of active pharmaceutical ingredients

Emerging Technologies Supporting Chemical Process R&D and Their Increasing Impact on Productivity in the Pharmaceutical Industry

“…This fact has spurred innovation in many high-throughput screening areas in the past few years, much of which has not yet appeared in the literature but has inundated the patent and trademark office. Some of the leading examples that have been published, in addition to crystallization, are solubility measurements ,− and chemical reaction and degradation kinetics. − More recently, high-throughput homogeneous and heterogeneous catalyst screening, which has been impacting the chemical industry for years, has begun to permeate the pharmaceutical arena. − Catalytic reactions can be extremely challenging on a small scale because of the very small amounts of catalyst required and sensitivity of the reactions to environmental and reaction parameters (e.g., mixing, pressure, temperature, oxygen and moisture in the air, etc.). This is especially true for heterogeneous catalytic hydrogenations because the reaction mixture exists as three physical phases.…”

“…Some of the leading examples that have been published, in addition to crystallization, are solubility measurements 45,[62][63][64][65][66] and chemical reaction and degradation kinetics. [67][68][69] More recently, highthroughput homogeneous and heterogeneous catalyst screening, which has been impacting the chemical industry for years, 70 has begun to permeate the pharmaceutical arena. [71][72][73][74] Catalytic reactions can be extremely challenging on a small scale because of the very small amounts of catalyst required and sensitivity of the reactions to environmental and reaction parameters (e.g., mixing, pressure, temperature, oxygen and moisture in the air, etc.).…”

Fast LC/MS in the analysis of small molecules

“…They use a fast linear gradient with a run time of 4 min. An automated workstation for the forced degradation of active pharmaceutical ingredients is described by Sims et al [90]. The drugs of interest are degraded in a parallel set-up from which samples are taken by a robot arm and transferred to the HPLC injector.…”

Application of an automated multi-pH and multi-temperature platform for accelerated solution stability testing in supporting drug discovery

“…Because this liquid formulation is often the most unstable form of a drug product, it can be useful to determine this worst case stability parameter early and to screen for relevant stability conditions. Discovery stability studies are typically carried out as a single data point by monitoring the drug solution before and after heating 12 or as a time course study, 13,14 while vendor provided automated system monitoring parent compound at different conditions and temperatures 15 are available. We have also developed an automated stability study platform where the compound may be tested simultaneously in six pH solutions and at two temperatures generating time course data within 20 h. Data are presented here for conditions between pH 1 and 10 at human body temperature (37 C) and at an elevated temperature (60 C), on a timeline capable of impacting the modern drug discovery design-make-test cycle.…”