Molecular Modelling to Support Drug Formulation for Small Molecule and Biologic Drugs

3/22/2022 11:50 - 12:20

  • Molecular modelling provides a basic understanding of the structure and behaviour of drugs as formulated that compliments experimental data and informs decision making in drug formulation
  • API and excipient physical and chemical property prediction for small molecule drug formulations
  • Characterization of drug-drug and drug-excipient association including drug-polymer interactions in small molecule and biologics formulations
  • Provide structural insights into concentrated protein solutions and predict viscosity, aggregation, and the effect of excipients

Complex and evolving structures, often in fluid states, play a crucial role in the pharmaceutical industry. Selecting and combining the right ingredients in the right manner to obtain optimal properties are essential for success given the inherent challenges and a competitive market. With advances in modern simulation techniques and computer hardware, molecular modelling is starting to provide timely and invaluable information that is complementary to experimental characterization.  We present a cross-section of capabilities available from Schrödinger’s for modelling either small-molecule drugs or biologics during the development process.   For small-molecule drugs workflows are available for characterizing degradation risk and crystal morphology as well as calculating elastic constants (bulk modulus, shear modulus, etc.), powder diffraction pattern, glass transition temperatures (Tg), diffusion constants, water adsorption, and solubility.   For biologics our toolset permits the prediction of structure, aggregation propensity, titration curves and isoelectric points, among other things.    For both small-molecule and biologics formulations powerful simulation tools using atomistic or coarse-grained models to permit the characterization of molecular interactions and nanoscale structuring, sometimes within otherwise disordered bulk systems (e.g., self-assembly of polymer-based structures, dissolving amorphous solid dispersions, liposomes and protein-excipient interactions). We will present some prototypical studies for both small molecule drugs and biologics.

John C. Shelley, Fellow, Schrödinger