Amorphous Drug Substances: Solid-State Opportunities and Considerations, Part 1
It is desirable to identify and develop a crystalline version of a drug substance from the perspective of API production, drug product formulation and manufacture, having established that satisfactory solubility, bioavailability and stability are achieved.
This is in effect the business requirement, in that both drug substance and product are efficacious and display chemical and physical stability. This is achieved via a reproducible manufacturing process to the drug substance and drug product formulation which is also straight forward to produce.
The number of drug candidates that are under pharmaceutical development which are found to be class II or IV under the Biopharmaceutical or Developability Classification Systems and are challenging from either a solubility or a solubility and permeability perspective are ever increasing. This can be a consequence of the complexity of these investigational compounds exceeding the ‘rule of five’.
The amorphous state of a new drug substance offers the opportunity to enhance solubility and bioavailability but can be challenging technically for pharmaceutical development.
The amorphous state of a solid material is the least thermodynamically stable and consequently, has the highest:
- free energy
- solubility in any solvent
- intrinsic rate of dissolution
- reactivity and bioavailability in the case of a drug substance
The last of these attributes is appealing for a drug product.
This then opens the scientific and technical challenges which have to be considered in relation to the amorphous state of a new drug substance under investigation.
Does the amorphous state of the material display suitable chemical and physical stability as the drug substance and in the drug product upon storage?
What additional processing considerations need to be established for the manufacture of the amorphous drug substance whilst maintaining the amorphous state in the production of the drug product reproducibly?
A rationale for the selection of the amorphous state of a compound has been explored for a new drug substance. The considerations for the development of an amorphous drug substance and progression to drug product will be examined.
MorphCryst Consulting can assist with solid-state science and development to progress your asset regardless of where your compound might be on the path to a marketed product.
