The Lab Notes

Permissible limits for impurities during clinical development has always been a grey area. Existing guidelines, specifically ICH Q3A only formally apply to marketed products.  How factors such as duration of clinical trials have never been effectively addressed.  A new paper looks in depth at how limits for impurities can be effectively linked to duration.  It…

Whereas process parameter risk quantification is conducted using mathematical calculations (Monte Carlo simulations) based on a process model, risk analysis is a semi-subjective methodology, of value for both early, as well as for late process development work. Herein we will focus on early process development, when little experimental information is available. In spite of its…

In the past, the particle size of finished APIs was mostly controlled by processes such as milling and micronization, but this often creates fines and can lead to formulation issues for some compounds. More recently companies are trying to control the particle size of the product as part of the crystallisation process (not forgetting that…

Industrial homogeneous catalytic processes are dominated by the use of expensive precious metals and rely on very efficient catalytic cycles for their cost effectiveness. Many of the processes carried out with precious metals are also achieved by iron catalysis, but often other processes compete and these chemistries have not been so widely used in industry,…

Meanwhile in another presentation from the 4th Winter Process Conference this time from Alexandra Parker of AstraZeneca discussed the development of the manufacturing route to make Lesinurad (Zurampic) a selective uric acid reabsorption inhibitor approved for treatment of hyperuricemia associated with gout in combination with a xanthine oxidase inhibitor (XOI) in patients unable to achieve…

We are always taught that molecules which can exist in a number of existing tautomeric forms may be prone to polymorph formation as a result, but I came across a real example at our recent Winter Process Conference held at the University of Strathclyde in Glasgow in a presentation from Ivan Marziano of Pfizer. The…

The Lindlar reduction of alkynes to alkenes is well known but does not always work as well as we would like, so any new method for carrying out this potentially useful reduction is always of interest. Grela and a co-worker found that Hoveyda-Grubbs HG metathesis catalysts in the presence of NaH (20 mol %) and…

The Ni or Pd catalysed Kumada-Corriu reaction between an aryl halide and a Grignard reagent is one of the original cross coupling reactions, and we all know that the Grignard reagent can react with suitable functional groups, such as carbonyls, on the aryl halide which limits it’s applicability.  Buchwald1 and Knochel2 have shown that by…

Normally when one chlorinates a phenol one would expect to see perhaps 8:1 to 10:1 regioselectivity in favour of the para-isomer, but in this paper using N-chlorosuccinimide as the chlorinating agent, using the correct thiourea catalyst can give up to much better regioselectivity for either the o-chloro or p-chloro isomer depending on the thiourea catalysts…

Those of you in the pharma industry will be familiar with the acronym NDA standing for New Drug Application, but there could be a new chemical use for NDA as the sodium equivalent of LDA (lithium diisopropylamide), although the authors use NaDA, so perhaps we should use LiDA instead of LDA.  In this paper David…