2025 Summit on Innovations in Controlled Release, Bioavailability Enhanceme

Amorphous solid dispersions (ASDs) are supersaturating formulations that enhance both the
apparent solubility, and the bioavailability of poorly water-soluble drugs following oral
administration. Upon dissolution, ASDs can generate nano-sized amorphous droplets of ∼100-
200 nm, when the concentration of the molecularly dissolved drug exceeds the amorphous
solubility, thereby maximizing the diffusive flux during the supersaturation window. In this
research, two poorly soluble drugs were prepared as ASDs with hydroxypropyl methylcellulose
acetyl succinate (HPMCAS), to characterize supersaturation and crystallization kinetics in
simulated and aspirated intestinal fluids. For each ASD, the onset of nucleation was found to be
highly medium dependent. Moreover, membrane flux was attributed to the resulting phase
behavior and remained high as long as supersaturation was maintained, whereas
desupersaturation, induced by drug crystallization, was coincident with a noticeable decrease in
flux. Importantly, it was shown that ASD dissolution in aspirated fluids led to the formation of
drug-rich nanodroplets, confirming same observations made in simulated fluids. These
observations provide insights into better understanding of the intraluminal supersaturation
potential of ASDs as well as the selection of appropriate dissolution media to improve
biopredictability for ASD formulations.

Lipid excipients offer tremendous in vivo performance benefits for oral drug delivery by improving solubility/bioavailability, enhancing absorption, and mitigating food effect. While lipids are typically employed in capsule formulations such as soft gels and liquid-filled hard capsules, there is growing interest in incorporating the benefits of lipid excipients into oral solid dosage forms, such as tablets.
 
In this presentation, we will provide an overview of how lipid excipients enhance bioavailability and discuss unique approaches to formulating oral solid dosage forms using well-known lipid chemistries.

Phil has been with digiM Solution since 2020 and is currently lead product specialist supporting microstructure characterization of oral solid dosage forms, with a strong focus on amorphous solid dispersions. Phil has a background in imaging ranging from diagnostic medical imaging in the field of dentistry to nanoscale imaging and microstructure characterization in the pharmaceutical industry. Phil is focused on the application of correlative image analysis to the optimization of pharmaceutical formulation, design, and performance assessment  Phil holds B.S. degrees in biomedical engineering from the University at Buffalo and biology from the University at Albany.