Kromasil^® notes

Kromasil preparative HPLC applications – success stories
2. Purification of orlistat

Obesity has developed into a severe, global health problem during the last decades, and as a result pharmaceutical companies have tried to develop a remedy for obesity, that can be used in combination with dieting and physical exercise. The one medication currently available and approved for long-term use is an anti-obesity drug marketed as Xenical or Alli. The API in the drug is Orlistat, also known as tetrahydrolipstatin.

Orlistat is the API in an anti-obesity drug marketed as Xenical or Alli in many countries. It is also known as tetrahydrolipstatin.

The drug is produced in very large scale, and for the chromatography 80 cm ID columns are routinely used. However, in many cases there is big room for improvement of the chromatographic conditions, to further increase productivity, and lower the separation cost.

The most common method today consists of a mobile phase of methanol/water, with a 100-120 Å C8 silica-based packing material. It is a very demanding separation, giving relatively low loading, and low productivity.

In order to overcome the problems with low loading and low productivity we, in the Separation Products group, carried out a method development project, where many different conditions were tested. The work resulted in a proprietary method where the productivity of orlistat could be increased by around 100%, as indicated in figure 2.

In both chromatograms above the same stationary phase is used, i.e. Kromasil 100-10-C8, and only the mobile phase is modified. In the improved method, just as in the insulin method mentioned previously, a positive displacement is used to push out the impurity, giving a possibility to collect almost all the orlistat (99%) with high purity (99.7%).

This example shows again the extreme importance of choosing the right conditions, in order to maximize throughput and productivity, and minimize cost!