High-speed vibrating milling, an opportunity for eco-compatible medicinal chemistry

The introduction of environmentally friendly methodologies is one of the priorities for pharmaceutical industry. Ball milling is an emerging technique in organic synthesis, allowing the reaction between solid compounds and reducing the environmental impact associated to the use of solvents.

18/07/2012

Img. 1: Ball mill
The introduction of environmentally friendly methodologies is one of the priorities for pharmaceutical industry. Ball milling is an emerging technique in organic synthesis, allowing the reaction between solid compounds and reducing the environmental impact associated to the use of solvents. The research group Heterocycles of biological interest of the Universidad Complutense de Madrid belonging to the i-Health cluster within the Moncloa Campus is currently involved in the application of this method to prepare new antitubercular agents.

A mill can be defined as an instrument for the grinding or pulverizing of grain and other raw materials. Historically, mills were powered by wind or water to mill grain for flour production. Ball milling is used for grinding and homogenizing mixtures of solids in the pharmaceutical, metallurgical, mining, painting and ceramics industries. In these machines, solids are placed in a rotating cylinder which is partially filled with balls and grinds material to the required fineness by friction and impact with the tumbling balls.

In the last years, small versions of ball mills have been created, known as High-Speed Vibrating Milling (HSVM) to be used in lower scale, mainly in laboratories. The functioning of these mills is based on the vibratory movement of the arm, which is attached to two metallic vessels that are covered on the inside with ceramics. Each of them contains a single ball made of inert material, as shown in the pictures. The equipment can be controlled from a display where time and frequency of the vibratory movement can be programmed. This type of mill makes the balls fall over the material up to 30 times per second.


Img. 2: Container and balls
The use this equipment for carrying out organic synthetic reactions is considered as a part of mechanochemistry, because the mechanical energy of the balls is employed for the induction of chemical processes. This type of reactions is innovative because the energy source for chemical reactions is usually thermal. In our laboratory, we apply this methodology to the preparation of compounds that are of interest in the treatment of tuberculosis. The development of new drugs in this field can be considered as an urgent need due to the significant increase of tuberculosis cases around the world and the appearance of resistant strains against currently known treatments.

In the last ten years, the number of patents and articles dealing with use of mechanochemistry in synthesis has increased exponentially. Among the advantages of this new technique, we highlight the possibility of carrying out reactions under solvent-free conditions, reducing the environmental, economic and security problems caused by their use. This technique is also advantageous for carrying out reactions involving insoluble starting materials.

Therefore, the use of ball milling is an innovative, effective and highly versatile technique in medicinal chemistry, with a low environmental impact, that will surely become an important method for the synthesis of bioactive compounds.

Author of the article: Verónica Estévez Closas

Tag: i-Health    Source: CEI Campus Moncloa

Event date:

18/07/2012