Sustainable pharmaceutical processes: how is a drug tablet manufactured?
Discover the expert speech of Jacques Fages and Romain Sescousse on drug tablet manufactured, professors and researchers at IMT Mines Albi and the RAPSODEE joint research center with the CNRS.
An interview with Jacques Fages and Romain Sescousse, professors and researchers at IMT Mines Albi and the RAPSODEE joint research center with the CNRS. Pr. Fages and Dr. Sescousse are respectively Director and Assistant Director of the Advanced Pharmaceutical Engineering (AdPharming) Masters Degree.
How is a drug tablet manufactured?
Tablets or capsules are powders that have been formulated into different shapes and sizes. Producing a pharmaceutical tablet is a relatively long, complex process including a whole sequence of manufacturing steps. Generally, the starting point is a liquid medium in which the active pharmaceutical ingredient (API) is in solution, and from the solution crystallization takes place. In other words, the API will appear in solid form. The solid must then be separated from the liquid for example by filtration. A pharmaceutical tablet contains very little API and mostly contains the excipient, i.e. a neutral diluent. In order to mix the API with the excipient, they need to have compatible properties. In particular they must be compatible in size. Using a classification step, the particle size range that will give a good mixture with the excipient is selected. Another step is needed to eliminate the finest particles to obtain good flow properties. This is achieved by wet granulation. A binder, often water, is added to granulate, i.e. to agglomerate all the particles until they are all of a size enabling them to be compressed. Generally a drying step is required. Compression gives the final shape of the tablet.
How is the pharmaceutical industry addressing environmental concerns?
With new continuous improvement tools such as QbD, or quality by design, PAT, “process analytical technology”, or “lean management”, industrial processes optimize time and manufacturing costs, and ensure quality while reducing waste or by-products. Respecting the environment is always a priority, for example by avoiding using toxic solvents. The aim is to eliminate all molecules that are toxic for humans and for the environment. Minimizing waste (the best waste is that which you don’t produce) and reducing environmental impact are taken into account right from the design stage.
Currently, the Covid Crisis has highlighted Europe’s dependence on China and India for both API’s and the formulation and manufacturing of many drugs. Do you think this is likely to change in the near future?
Today, China and India in particular are very large manufacturers of APIs and generic drugs and there is a new awareness of this dependence. This is somewhat paradoxical as the big global pharmaceutical companies are still European or American. However, the manufacturing of their APIs is gone. Relocating production and hence reindustrialization in a country such as France is being envisaged. But while public opinion is in support of local production, there are still a lot of obstacles to overcome before it becomes a reality.
The drug market in the United States and in Europe is stable, while in India and in China it is fast growing, as it is in all emerging countries. It makes sense that in the places where there is growth, there should be manufacturing plants on site, but the geographical distribution must be harmonious so that patients all over the world can be treated fairly and equitably.
What has the Covid crisis revealed?
The speed with which scientists have sequenced the genome of the virus and then were able to implement totally new technologies such as the messenger RNA vaccine is exceptional. Efficient vaccines have been obtained in less than a year after the crisis. This was totally unthinkable just a few years ago. The crisis has highlighted the amazing advances in genetics and molecular biology. Very shortly after the appearance of the new variant of the coronavirus in the United Kingdom, we have tests that are capable of detecting specific genes of this variant. The crisis has highlighted the remarkable progress achieved in these sciences in recent years.
Can you tell me about the AdPharming Masters program?
We are part of the RAPSODEE research center which works on powders, divided solids, energy and the environment. The purpose of the AdPharming master is to train scientific managers in both technical and management skills. Our students are equipped to work in an international context and they know the particular characteristics of the pharmaceutical industry. During the first semester, they study basic sciences and process engineering then they tackleskills and knowledge specific to the pharmaceutical industry such as powder mixing, which is a science in its own right. These processes are taught by researchers from RAPSODEE and by specialists from industry. In the final semester they complete an internship in the pharmaceutical industry or in a research laboratory. The program covers all the skills required to work in the pharmaceutical industry. In addition to a strong foundation in pharmaceutical processes, there are courses on regulations, project or risk management, “lean management”, modelling tools, good manufacturing practices (GMP) and intercultural communication. Our students come from all over the world and will graduate fully prepared to work on teams with people from diverse cultures and backgrounds.