Thermo Fisher Pairs In Silico Modeling With an Expanded ASD Toolbox at AAPS PharmSci 360

At AAPS PharmSci 360 2026 in New Orleans, scientists from Thermo Fisher Scientific described how the company pairs in silico modeling with a range of solubility-enhancing technologies to move poorly soluble drug candidates from feasibility to commercial manufacturing.¹ The partner presentation was delivered by Andrew West, staff scientist, science and innovation, and Ramesh Muttavarapu, MS, MBA, global subject matter expert. It covered spray drying, hot melt extrusion (HME), lipid-based formulations, and KinetiSol, a solvent-free amorphous solid dispersion (ASD) technology the company added this year.¹,²

For more on the meeting, see the BioPharm International® PharmSci 360 preview.

Why is solubility still a bottleneck?

West estimated that about 90% of small molecules have a solubility challenge, at a time when development teams face shorter timelines and pressure to use less API.¹ Among technologies used in commercial approvals, he said, ASDs began gaining popularity in commercial approvals.¹

Solubility problems can surface as poor exposure in phase 2, and phase 3 tests whether the manufacturing process can scale, he said. “When we’re selecting a formulation early on, the three things you really need to focus on are improving solubility, ensuring we can make it manufacturable, and also ensuring that the formulation is stable,” West said.¹

How does in silico modeling guide technology selection?

Thermo Fisher’s Quadrant 2 platform uses API properties, such as melting point, glass transition temperature, log P, and molecular weight, along with dose, to rank technologies in three tiers: likely to work, worth evaluating in the lab, or unlikely to succeed.¹ Lab results are fed back into the model. According to Thermo Fisher, the platform has been applied to more than 400 molecules.³

In one case study, Quadrant 2 placed a compound in Developability Classification System class IIb, meaning its absorption was solubility limited. Molecular dynamics simulations then identified four lead polymers and a maximum drug loading.¹ The team spray dried about 5 g of each formulation at low and high drug loadings and screened them for dissolution, physical and chemical stability over 4 weeks of accelerated conditions, and manufacturability. A 20% drug load with hydroxypropyl methylcellulose acetate succinate (HPMCAS) was selected, and the program reached the clinic in about 7 to 8 months.¹

“There’s not always one clear winner, and you really need to understand the risks associated with each,” West said.¹

A second case study addressed a roughly tenfold scale-up in batch size. A design of experiments on a pilot-scale spray dryer varied outlet temperature, relative saturation, and feed pressure. Dissolution performance was consistent across conditions, and all dispersions remained amorphous, West said.¹

What role do lipids and HME play?

Muttavarapu outlined softgel and liquid-filled hard capsule processes, then described an HME technology transfer from a client’s commercial facility. “We treated tech transfer as a process understanding exercise, not as a simple tech transfer,” he said.¹ The team monitored barrel temperature, melt temperature, screw design, and throughput, and confirmed that the intermediate remained amorphous through milling, blending, compression, and coating.¹ That approach reflects long-standing guidance on transfers. “The main goal of tech transfer is to transfer the product and process with minimal or no changes, which will minimize regulatory challenges and smooth the path to regulatory approval,” said Joe Masi, then senior director of manufacturing science and technology at Cambrex, in a 2018 BioPharm International Q&A on scaling formulations from small-scale batches to commercial production.

Where does KinetiSol fit?

In June 2026, AustinPx announced that it would install KinetiSol equipment at Thermo Fisher’s sites in Bend, Oregon, and Cincinnati, Ohio, making Thermo Fisher the exclusive third-party contract development and manufacturing organization offering the KinetiSol Formulator.² In September, FDA’s Center for Drug Evaluation and Research granted the technology Advanced Manufacturing Technology designation.⁴

KinetiSol relies on shear generated within the system rather than solvents or external heat, and processing takes about 10 to 20 seconds, Muttavarapu said.¹ He described it as a fit for APIs that have poor organic solvent solubility and high melting points, or that degrade during HME. The lab-scale Formulator is already installed at Bend, and a late-stage Compounder is planned for Cincinnati in the first quarter of 2027, or the second quarter at the latest.¹ He also cited a published study in which KinetiSol dispersions of abiraterone, a drug with a high melting point and poor organic solvent solubility, increased bioavailability up to 13.8-fold compared with a generic abiraterone acetate tablet.¹,⁵

What did the audience ask?

Asked whether log P can guide technology selection, West said high-log P compounds often suit lipid formulations but tend to require lower drug loading in dispersions, typically around 25%.¹

References

1. Muttavarapu R, West A. Expanding the formulation toolbox: scalable solutions for solubility & bioavailability enhancement. Partner presentation at: AAPS PharmSci 360; October 2026; New Orleans, LA.
2. AustinPx. AustinPx expands KinetiSol technology commercial access through Thermo Fisher Scientific collaboration. Press release. Published June 30, 2026. Accessed October 27, 2026.
3. Thermo Fisher Scientific. AI-driven drug development for poor solubility and bioavailability. Accessed October 27, 2026.
4. AustinPx. AustinPx’s KinetiSol technology receives FDA Advanced Manufacturing Technology designation. Press release. Published September 15, 2026. Accessed October 27, 2026.
5. Gala U, Miller D, Williams RO. Improved dissolution and pharmacokinetics of abiraterone through KinetiSol enabled amorphous solid dispersions. Pharmaceutics. 2020;12(4):357. doi:10.3390/pharmaceutics12040357. Published April 14, 2020. Accessed October 27, 2026.