The majority (~90%) of new chemical entities (NCEs) discovered by the pharmaceutical industry today are poorly soluble or lipophilic compounds; as are about 40% of existing drugs in the market. Consequently, this can create major challenges in drug development due to poor solubility, short biological half-life, poor bioavailability, prominent adverse effects, and stability of NCE’s.
Nanosuspensions have emerged as an effective strategy for the delivery of hydrophobic drugs because of the unique versatility and advantages in formulation. Adaptive Focused Acoustics can be used to create nanosuspensions through the complete life cycle from discovery through first human trials. By enabling closed vessel, contamination free wet milling in a scalable manner, early stage compounds can be dosed and evaluated, without extensive Formulation development, with a very minimal amount of material. Subsequent trials can be completed with the same technology through the preparation of larger volumes of nanosuspension sample material.
The Covaris Focused Ultrasonicator, has successfully demonstrated the ability to mill small volumes of early stage material into nanosuspensions suitable for animal dosing. Volumes as low as 100ul are possible with 100% recovery of the material.
Features & Benefits
Eliminates molecular thermal damage by maintaining isothermal sample temperatures during the process
Scales from bench-top screens through clinical studies (micro-liters to 1,000+ liters) Compatible with Quality By Design and Process Analytical Technology
Enables sterile, closed, single-use fluid circuits which eliminate carryover Enables disposable wetted surfaces which minimizes impurities
Standardizes the process application of industry-proven AFA technology Automated process by minimizing subjective operator influence
Improves processing performance (from 2 days to 2 minutes) Increases solubility and stability
Solidification of Nanosuspension via Spray Granulation. Yidan Lan et al, AAPS 2012 Poster presentation. Demonstrated the feasibility of combining AFA technology (to produce nanosuspension by Tops down milling) and spray granulation.
SEM before and after wet milling
Wet milling of 2ml Felodipine
250ml nanosuspension preparation
Bead mill comparative run: 6 hours AFA achieves similar distribution as 24 hour bead milling
Covaris provides tools and technologies to improve pre-analytical sample preparation, enable novel drug formulations, and manage compounds in the drug discovery process.