Abstract
This in-silico feasibility analysis discloses, as defensive prior art (CC BY 4.0), a hypothetical lyophilized insulin formulation engineered for amorphous trehalose-glass storage to remove the 2-8 C cold chain that constrains this WHO Essential Medicine. No wet-lab potency, stability, or bioequivalence data are generated; all numerical predictions are computational extrapolations from peer-reviewed parameters. The formulation is pre-formed Zn2+ R6-hexamer insulin embedded in an amorphous trehalose-dihydrate matrix (about 83% w/w of solids), with L-proline as a freeze-stage co-lyoprotectant (about 2-3%) and D-mannitol as a crystalline bulking agent (about 12-15%), reconstituted subcutaneously on use. Feasibility is assessed through five analyses: an activation-energy Bayesian prior from published solid-state insulin kinetics (Pikal & Rigsbee 1997; Sadrzadeh 2010; Lai & Topp 1999); a PyMC NUTS shelf-life posterior of monomer retention; a Couchman-Karasz mixed-glass transition temperature (Tg about 91 C anhydrous, tolerating residual moisture to about 2.8%); a Tang-Pikal lyophilization-cycle design (shelf <= -32 C, <= 50 mTorr, 5-7-day cycle); and a trehalose-protein molecular-dynamics literature synthesis supporting the matrix-invariance approximation. The benefit is a cheap, generic, off-patent, cold-chain-independent insulin presentation kept in the public domain. Limitations include overlapping prior art (US 20170340738), pooled cross-matrix activation-energy anchors, absent ICH Q1A/Q5C real-time data, trehalose-dihydrate crystallization risk requiring desiccant co-packaging, and an impractical non-incumbent BLA pathway (realistic route: WHO Emergency Use Listing). This is a prior-art disclosure, not deployment, regulatory, or clinical guidance.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Recommended Citation
chuenglertsiri, chaiyapat and Chen, Pattrick, "Computational Assessment of Lyophilized Insulin Stability in a Trehalose–Mannitol Matrix: Bayesian Shelf-Life Modeling from Published Solid-State Kinetic Data with Trehalose–Insulin Molecular Dynamics Literature Synthesis", Technical Disclosure Commons, ()
https://www.tdcommons.org/dpubs_series/10549