Thalidomide, the sedative that was found to cause birth defects if used early in pregnancy, contained two forms of thalidomide molecule. They were mirror images, called optical isomers, that were synthesized simultaneously in the manufacturing process. One isomer, it was later found, produced the sedative effect while the other caused the defects.
Isomers form automatically when many drugs are made. And the wrong isomer can cause unwanted side effects. So a Texas Tech University chemist has found a way to separate the two forms. If the method can be applied to mass production, the result may be purer forms of drugs that are less likely to cause side effects.
About 60 percent of prescription drugs are mixtures of the two isomers of their active ingredient. In most cases this causes no problem, but in about 25 percent of drugs the harmful effects of the bad isomer limit the allowable dose of the good isomer.
Isomeric molecules are made up of exactly the same kinds and numbers of atoms, but the atoms are bound into combinations that look like mirror images of one another. Conventional manufacturing processes usually produce a 50-50 mixture of the two forms.
Right and left hands are, in a sense, isomers of each other. The shape of a molecule usually helps determine how it reacts with other molecules. Therefore, a "left-hand" drug molecule may be useless if the desired action is to fit into a "right-handed glove" molecule in the body. Worse, the left-hand molecule may cause harm by reacting with some other molecule that needs to be left alone.
The new process, developed by Daniel W. Armstrong, is essentially a filter that holds back one of the two isomers. It consists of a glass tube containing fine particles of silica gel coated with a substance called cyclodextrin. A solution of the drug, containing both isomers, is pumped through the tube and the cyclodextrin, in effect, holds one isomer while letting the other pass.
The method, which has been patented, works in the laboratory. Researchers at several centers hope to develop it for large-scale processing.