Attività

Understanding the effect of API changes in pharmaceutical processing
There is, of course, the natural curiosity of the scientist to understand what they are working with, and how the molecule’s journey influences its performance. The regulators who control medicines for the benefit of the patients who take them also require an understanding of what is happening to the drug molecules and particles. These two interests combine in Quality by Design (QbD) initiatives, where scientists and regulators come together to provide a thorough understanding of the manufacturing process of a dosage form, to ensure that it is effective and fit for purpose.

Over the past few years there have been significant scientific advances in understanding how a molecule joins, and is incorporated into, the crystal that is its home until it reaches the gastric intestinal (GI) tract. Despite the fact that the instant of nucleation remains a moment of magic or mystery, the growth of a crystal can be followed, understood and modelled and the process of isolating and drying formed crystals has been closely studied.

The milling process has opened itself to greater understanding in recent years, such that the mechanism and extent of crystal fracture can be followed, and the properties of the resultant particles predicted with greater accuracy. We can characterise the end material, with its single particles, agglomerates or aggregates by size, shape and surface area, and examine them in detail using microscopy techniques. At the end of the particles’ journey to the dosage form we can follow the disintegration of the dosage form and the dissolution of the particles in a range of model media. This data can be combined with other observations to develop models of how drugs will reach the bloodstream and eventually be eliminated.

Characterisation challenges
The use of chemical imaging to investigate the distribution of single components with a formulated sample have previously been reported2. However, due to limitations in the optical resolution of such systems, the individual particle sizes cannot be directly measured; pixels often contain more than one of the constituents. Pixels are instead colour coded to indicate the relative concentration of each constituent, thus enabling identification of ‘domains’ (areas of high component concentration). The relationship between domain size and particle size can be affected by multiple factors such as homogeneity, aggregation and morphology.
http://www.nmn-bio.com/intermediate-api/