Knowledge of the compressive mechanical properties of battery separator membranes is important for understanding their long term performance in battery cells where they are placed under compression. This paper presents a straightforward procedure for measuring the compressive mechanical properties of battery separator membranes using a universal compression testing machine. The compressive mechanical properties of a microporous polypropylene separator are characterized over a range of strain rates and in different fluid environments. These measurements are then compared to measurements of the rate and fluid-dependent mechanical properties of the separator under tension. High strain rate dependence due to viscoelasticity is observed in both tension and compression. An additional rate dependence due to poroelastic effects is observed in compression at high strain rates. A reduction in mechanical properties is observed in DMC solvent environments for both tension and compression, but is found to be less pronounced in compression. The difference in mechanical properties between compression and tension highlight the anisotropic nature of battery separators and the importance of measuring compressive properties in addition to tensile properties. The battery separator is a porous polymer membrane used to create a physical barrier between electrodes in a battery cell. The separator must be mechanically robust to ensure safe operation over the cell's service life: mechanical failure leading to electrode contact can result in catastrophic failure of the cell.1-3 Such failure often follows from puncture or thermal shrinkage of the membrane.4-6 Non-catastrophic battery failure through the form of accelerated degradation can also result from separator deformation. [7][8][9] The importance of the mechanical properties of the separator with respect to battery safety and durability has consequently motivated much research on the mechanical properties of battery separators.Previous works on the mechanical properties of separator have mainly investigated the mechanical properties under tension. [10][11][12][13][14] While knowledge of the tensile properties of the separator are important from a manufacturing standpoint, where the separator is placed under tension during cell assembly, the tensile properties are less relevant for general battery operation. This is because the separator is placed under compression during typical battery operating conditions, where it is compressed in the direction normal to the plane of the large separator face by the anode and cathode. This compressive stress is cyclic owing to reversible electrode strains and gradually increases during operation as a result of irreversible volumetric increases occurring on the electrodes. 9,15 These stack stresses during operation have been observed to be on the order of 1MPa in previous work, 9,15,16 although the presence of geometric non-uniformities (e.g. particles and curved faces) can result in local stresses that are significantly higher. 17-19The mechanical...

Over the past decade, formulation predictive dissolution (fPD) testing has gained increasing attention. Another mindset is pushed forward where scientists in our field are more confident to explore the in vivo behavior of an oral drug product by performing predictive in vitro dissolution studies. Similarly, there is an increasing interest in the application of modern computational fluid dynamics (CFD) frameworks and high-performance computing platforms to study the local processes underlying absorption within the gastrointestinal (GI) tract. In that way, CFD and computing platforms both can inform future PBPK-based in silico frameworks and determine the GI-motility-driven hydrodynamic impacts that should be incorporated into in vitro dissolution methods for in vivo relevance. Current compendial dissolution methods are not always reliable to predict the in vivo behavior, especially not for biopharmaceutics classification system (BCS) class 2/4 compounds suffering from a low aqueous solubility. Developing a predictive dissolution test will be more reliable, cost-effective and less time-consuming as long as the predictive power of the test is sufficiently strong. There is a need to develop a biorelevant, predictive dissolution method that can be applied by pharmaceutical drug companies to facilitate marketing access for generic and novel drug products. In 2014, Prof. Gordon L. Amidon and his team initiated a far-ranging research program designed to integrate (1) in vivo studies in humans in order to further improve the understanding of the intraluminal processing of oral dosage forms and dissolved drug along the gastrointestinal (GI) tract, (2) advancement of in vitro methodologies that incorporates higher levels of in vivo relevance and (3) computational experiments to study the local processes underlying dissolution, transport and absorption within the intestines performed with a new unique CFD based framework. Of particular importance is revealing the physiological variables determining the variability in in vivo dissolution and GI absorption from person to person in order to address (potential) in vivo BE failures. This paper provides an introduction to this multidisciplinary project, informs the reader about current achievements and outlines future directions.

There is growing need to develop efficient methods for early-stage drug discovery, continuous manufacturing of drug delivery vehicles, and ultra-precise dosing of high potency drugs. Here we demonstrate the use of solvent-free organic vapor jet printing to deposit nanostructured films of small molecular pharmaceutical ingredients, including caffeine, paracetamol, ibuprofen, tamoxifen, BAY 11-7082 and fluorescein, with accuracy on the scale of micrograms per square centimeter, onto glass, Tegaderm, Listerine tabs, and stainless steel microneedles. The printed films exhibit similar crystallographic order and chemistry as the original powders; controlled, order-of-magnitude enhancements of dissolution rate are observed relative to powder-form particles. In vitro treatment of breast and ovarian cancer cell cultures in aqueous media by tamoxifen and BAY 11-7082 films shows similar behavior to drugs pre-dissolved in dimethyl sulfoxide. The demonstrated precise printing of medicines as films, without the use of solvents, can accelerate drug screening and enable continuous manufacturing, while enhancing dosage accuracy.

Preclinical evaluation of modern oral dosage forms requires more advanced in vitro devices as the trend of selecting low solubility, high permeability compounds for commercial development continues. Current dissolution methodologies may not always be suitable for such compounds due to excessive fluid volume, high fluid shear rates, heterogeneity of shear rates, suboptimal fluid flow, and, ultimately, the lack of absorption ability (The Science of USP 1 and 2 Dissolution: Present Challenges and Future Relevance Gray Pharmaceutical Research20092612891302). Herein, a new dissolution apparatus is introduced in combination with an ultrathin, semipermeable polymer membrane that mimics human passive absorption for lipophilic compounds. The ultrathin large-area polydimethylsiloxane (PDMS) membrane (UTLAM) absorption system is designed to mimic the dissolution and passive transcellular diffusion process representing the oral absorption pathway. A simple spin-casting method was developed to fabricate the ultrathin highly uniform membranes. To minimize membrane resistance to diffusion and maximize transport across the polymer membrane, 10–40 μm PDMS membranes were successfully prepared. A new diffusion cell was designed and tested to support the UTLAM and incorporates a hydrofoil impeller for more desirable hydrodynamics and mixing, using ibuprofen as a model weak acidic drug. UTLAM permeability was sufficiently high that the aqueous boundary layer contributed to the overall permeability of the system. This diffusion cell system demonstrated that, when the aqueous diffusion layer contributes to the overall resistance to transport, the pH at which absorption is 50% of maximum (pH50%) shifts from the pK a to higher values, demonstrating why weak acid drugs can exhibit high absorption at pH’s significantly greater than their pK a. High rates of transport across the UTLAM are possible for drugs with high partition coefficients (i.e., BCS II compounds even under mostly ionized conditions), and PDMS UTLAMs may be tailored to simulate human intestinal passive absorption rates.