Drug Substance vs. Drug Product

Whether you're developing an NCE (new chemical entity) or the generic version of a marketed drug, it’s helpful to understand the difference between drug substance and drug product.

What are 'drug substance' and 'drug product'?

Drug substance refers to the unformulated API (active pharmaceutical ingredient). The API has the therapeutic effect in the body as opposed to the excipients which assist with the delivery of the API. The chemical purity and physical state (crystal form) influence the quality and performance of a drug substance. This is especially important for water insoluble drugs. 

Drug product is the formulated drug substance with excipients. These excipients do not have a therapeutic effect but can influence the delivery of the drug substance. The drug product is typically the final marketed dosage form of the drug substance for example a tablet or capsule. 

Which in vitro tests are carried out on drug substance/drug product?

To develop a drug product (the marketed form of the drug) from a drug substance, it’s important to know the physicochemical properties and solubility of the drug substance. Biorelevant solubility testing of the drug substance is performed to understand the drug’s likely in vivo solubility which can be used to guide the selection of the appropriate physical form and formulation strategy.

Once the drug substance is formulated into a drug product, the formulation can be tested in suitable media (biorelevant/physiologically relevant media) for dissolution testing prior to clinical studies. When conducted correctly, this in vitro biorelevant dissolution testing will indicate how a drug product would dissolve and behave in vivo. 

Summary

Drug substance is the unformulated API and drug product is the formulated (marketed) drug. Results from in vitro biorelevant solubility tests of drug substance and in vitro dissolution tests of drug product can be of huge benefit during development because they provide valuable insights into likely in vivo behaviour.