Case Study III
NCE bioavailability enhancement using a SMEDDS formulation
Our customer required the development of a lipid-based oral formulation with the desired objectives of improving the oral bioavailability of their drug.
The Challenge & Our Approach
The challenge in this Case Study is typical of what many companies come across when confronted with poorly water soluble API’s that fall within BCS Class II and exhibit low solubility and high permeability. It is estimates that around 70% of NCE’s entering discovery and development programmes are within this class.
In close consultation with our customer, we agreed a formulation development strategy that was focused on the self micro-emulsifying delivery systems (SMEDDS) which involved measuring the kinetic solubility of the API in a set of galenical excipients having differing hydrophobic lipophilic balance (HLB) values.
This is demonstrated in the in vitro dissolution behaviour of the Lipid based formulations, of these the SMEDDS-1 retains almost 100% of the dissolved active. The oral PK results correlate with the in vitro findings that confirm that the improved solubility may have led to the improved oral exposre in vivo.
This case study provides further details of our approach, data and final formulation choice.
The following conclusions were made at the end of this project:
- The SMEDDS developed showed a significant increased rate of dissolution of the active in a bio-relevant media (FaSSIF).
- A two-fold increase in oral exposure was observed with SMEDDS-1 Capsules.
- Long term physical and chemical stability of the lipid based formulation was required.