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Pre-formulation
From a solid with unknown properties to an IND-ready formulation, usually in 8 to 12 weeks.
The developability problem
A compound that is active in the assay may not dissolve, may not be stable in solution, or may need a dose that will not fit in a capsule a patient can swallow.
Each of those is a formulation problem, and the technology chosen to solve it is difficult to change once the IND-enabling work has started.
Unsatisfactory physicochemical properties lead to low solubility, low permeability and poor bioavailability, and to high toxicity, poor efficacy, and manufacturing difficulty. Pre-formulation studies select the most developable molecules at the preclinical stage, develop the preclinical formulations that support PK, PD, and toxicology studies in animals, and set the formulation strategy for clinical development.
The IND-enabling pre-formulation package
An integrated developability assessment that ends with an IND-ready formulation, typically in 8 to 12 weeks.
- Bioavailability technologies screened in parallel, so the selection is made by direct comparison
- An animal PK study included, which gives a measured exposure figure
- In vitro, in vivo and in silico work in one place, with one point of contact
- High-potency compounds, PROTACs, peptides and oligonucleotides run through the same assessment
The package operates alongside WuXi AppTec’s medicinal chemistry, DMPK, pharmacology, toxicology and bioanalysis facilities.
Profiling
pKa, LogP, thermal transitions (Tm, Tg, Tc, Td), solubility, supersaturation, forced degradation, solution and solid stability, photostability, excipient compatibility.
Physical form work runs alongside: recrystallization, polymorph, and salt or co-crystal selection.
Preclinical formulation
Preclinical formulation screening and selection, and the formulations used for PK and toxicology studies.
Where bioavailability needs enhancing, the options are spray-dried dispersion, hot melt extrusion, lipid-based emulsion, nano suspension and micronization by jet milling.
In silico prediction
Developability prediction, DCS and BCS classification, food-effect and acid-reducing-agent interaction prediction, and GastroPlus modeling, used to decide which experiments are worth running.
Developability answers on minimal material
Early formulation work happens when API is scarcest. The pre-formulation package is built to give a developability answer on milligrams of material, before a campaign is committed to finding it at scale.
Pre-formulation laboratories are at the Shanghai Waigaoqiao and Wuxi City sites, each with its own formulation and analytical teams.