Milk Protein-Based Amorphous Solid Dispersion for Delivery of Hydrophobic APIs

We intend to demonstrate that casein proteins from bovine milk can be used to create amorphous solid dispersions (ASD) of insoluble active pharmaceutical ingredient (API). These casein-based API-ASD can be readily dispersed in water and used as ethanol-free oral liquid formulations for infants and children. In this proposal, first we will elucidate the key environmental stimuli conducive to the formation of casein-based ASD with high loading capacity, and excellent instant properties. The core of the experiments will be conducted using ritonavir, furosemide, and tristearin as hydrophobic probes. Second, we will determine the stability and release kinetics of ASD in response to pH and to model digestion systems. We will investigate the environmental stimuli leading to the delivery of the API form the ASD to the aqueous phase. Third, we will determine the in vivo bioavailability of one casein-based ritonavir ASD and one casein-based furosemide ASD. We will formulate the two ethanol-free API ASD, disperse in water, and administrate to mice models to determine bioavailability vs. commercial formulations containing ethanol. The latter experiments will demonstrate that API-ASDs are dispersible in an aqueous phase and exhibit appropriate absorption through the intestinal lumen. Project Number: 1R21HD117135-01 | Fiscal Year: 2025 | NIH Institute/Center: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) | Principal Investigator: Federico Harte | Institution: PENNSYLVANIA STATE UNIVERSITY, THE, UNIVERSITY PARK, PA | Award Amount: $428,208 | Activity Code: R21 | Study Section: Special Emphasis Panel[ZRG1 MCST-M (81)] View on NIH RePORTER: https://reporter.nih.gov/project-details/1R21HD11713501