Aprepitant - Drug Development

Drug Development

Once the effective synthesis of aprepitant was discovered, the next step taken by Merck was to develop a pharmaceutical drug that incorporates the active substance in it.

Researches began to analyse aprepitant and make observations about its chemical and physical properties. It was discovered that the substance has a low aqueous solubility. As a result of this the product development focused on reducing the size of aprepitant’s particles to a nanoscale. This therefore would increase the bioavailability of the drug.

Using this information Merck came up with a manufacturing process, (which is still used today). This nine step process includes wet milling, which reduces the particle size of the active ingredient. It also involves excipients being used to keep the nanoparticles of aprepitant separated from each other during and after the microcrystalline celluse beads being coated. This therefore prevents agglomerating of the beads, which means that nanoparticles of aprepitant remains small even after it is re dispersed from the beads.

The nine-step manufacturing process involves

• A slurry of aprepitant, hydroxypropyl cellulose, and water being produced
• The slurry undergoing pre-milling
• An aqueous sucrose dispersion being added to the slurry
• The slurry undergoing media-milling that produces a colloidal dispersion
• An aqueous sucrose dispersion being added to the slurry
• The microcrystalline cellulose beads being spray coated with the colloidal dispersion.
• The coated beads being sieved
• The coated microcrystalline cellulose beads are blended with micronised sodium lauryl sulfate
• The blended beads are encapsulated

The end result of the nine step process is a capsule, known as Emend, which contain aprepitant. The capsule also contains several other substances, which includes sucrose, hydroxypropyl cellulose, microcrystalline cellulose, sodium lauryl sulfate, gelatin, shellac, black iron oxide and titanium dioxide.