“… most NCEs are poorly water soluble drugs, not well-absorbed after oral administration and the oral delivery of such drugs is frequently associated with low bioavailability, high intra- and inter-subject variability, and a lack of dose proportionality … It has been estimated that 40% of new chemical entities currently being discovered are poorly water-soluble.”
– Saffoon et al., J Appl Pharm Sci. 2011; 1: 30
In March 2014, the FDA created guidelines on how to document bioavailability of IND and NDA drugs. Optimal bioavailability is important for high efficacy, but bioavailability can be poor in oral drugs. Three strategies for improving oral bioavailability of drugs are amorphous solid dispersions, nanoparticulates and self-emulsifying drying systems.
Amorphous solid dispersions are one method that can enhance bioavailability of oral drugs. Amorphous solid dispersions can be created through fusion, spray congealing and rapid solvent evaporation, such as spray drying and freeze drying. Advantages of amorphous solid dispersions are improved wettability, higher porosity, reduced particle size and higher solubility. A disadvantage is less stability due to aging, moisture and temperature.
Nanoparticulates are a second technique that can improve oral bioavailability. Nanoparticulate systems include those made from oils, lipids and biocompatible polymers. The most promising seem to be solid lipid nanoparticles, which can enhance oral bioavailability to two to twenty-five times its original state. Advantages of solid lipid nanoparticles are increased drug stability, lower cost and ability to scale up production. Disadvantages are particle growth and possible burst release.
A third way to improve bioavailability of oral drugs is to use self-emulsifying drying systems. Oil, surfactant, cosurfactant and the API are combined into an isotropic mixture to form self-emulsifying drug delivery systems. Some advantages to this system are the ease of manufacturing and scaling up and the ability to increase drug loading. A disadvantage is the amount of surfactant can lead to gastrointestinal adverse events.
Amorphous solid dispersions, nanoparticulates and self-emulsifying drying systems are three strategies for enhancing bioavailability of oral drugs. Orbis Biosciences uses Precision Particle FabricationTM technology, which produces uniform microparticles and microcapsules with narrow size distribution and precise control over particle structure. If these methods continue to be used and improved, patients will receive more efficient, more efficacious medicine.