Rapid preparation of pharmaceutical co-crystals with thermal ink-jet printing

Thermal ink-jet printing (TIJP) is shown to be a rapid (minutes) method with which to prepare pharmaceutical co-crystals; co-crystals were identified in all cases where the co-formers could be dissolved in water and/or water/ethanol solutions

Biocatalytic synthesis of highly ordered degradable dextran-based hydrogels

We have prepared unique macroporous and ordered dextran-based hydrogels using a single-step biocatalytic transesterification reaction between dextran and divinyladipate in neat dimethylsulfoxide. These hydrogels show a unimodal distribution of interconnected pores with average diameters from 0.4 to 2.0 [mu]m depending on the degree of substitution. In addition, the hydrogels show a higher elastic modulus for a given swelling ratio than chemically synthesized dextran-based hydrogels. In vivo studies in rats show that the hydrogel networks are degradable over a range of time scales from 5 to over 40 days, and possess good biocompatibility, as reflected in only a mild inflammatory reaction and minor fibrous capsule formation during the time-frame of subcutaneous implantation. These combined properties may offer competitive advantages in biomedical applications ranging from tissue engineering to controlled drug delivery.http://www.sciencedirect.com/science/article/B6TWB-4F7Y94V-3/1/0d83788c215a34850e13d6d76d3bba8

Fine-tuning of a thermosalient phase transition by solid solutions

Thermosalient crystals are solids that exhibit motion at the macroscale as a consequence of a thermally induced phase transition. They represent an interesting scientific phenomenon and could be useful as actuators for the conversion of thermal energy into motion or mechanical work. The potential utilization of these miniature transducers in real-world devices requires a controllable phase transition (i.e. a predetermined temperature). While it is difficult to control these performances with a single-component molecular crystal, “tunable” properties could be accomplished by solid solutions. To verify this hypothesis, the thermosalient material [Zn(bpy)Br2] (bpy = 2,2′-bipyridine) was selected and its synthesis was performed in the presence of chloride ions. The resulting mixed crystals ([Zn(bpy)Br2xCl2(1−x)]) show that the product undergoes the expected thermosalient phase transition, and the temperature of the onset of the phase transition and the transition enthalpy depend on the Cl/Br ratio

3-Amino­pyridin-1-ium 3-carb­oxy­benzo­ate

In the title organic salt, C5H7N2 +·C8H5O4 −, the carb­oxy­lic group is nearly coplanar with the benzene ring [dihedral angle 1.9 (4)°] whereas the carboxyl­ate group is twisted relative to the benzene ring by 13.6 (4)°. In the crystal, N-H⋯O and O—H⋯O hydrogen bonds connect the components into a three-dimensional framework consisting of stacks of alternating pairs of anions and cations exhibiting π–π stacking inter­actions with centroid–centroid distances in the range 3.676 (2)–3.711 (1) Å. The π–π stacks extend along [110] and [-110]

Deducing chemical structure from crystallographically determined atomic coordinates

An improved algorithm has been written for assigning chemical structures to incoming entries to the Cambridge Structural Database

The Storage and In-Use Stability of mRNA Vaccines and Therapeutics: Not A Cold Case

The remarkable impact of mRNA vaccines on mitigating disease and improving public health has been amply demonstrated during the COVID-19 pandemic. Many new mRNA-based vaccine and therapeutic candidates are in development, yet the current reality of their stability limitations requires their frozen storage. Numerous challenges remain to improve formulated mRNA stability and enable refrigerator storage, and this review provides an update on developments to tackle this multi-faceted stability challenge. We describe the chemistry underlying mRNA degradation during storage and highlight how lipid nanoparticle (LNP) formulations are a double-edged sword: while LNPs protect mRNA against enzymatic degradation, interactions with and between LNP excipients introduce additional risks for mRNA degradation. We also discuss strategies to improve mRNA stability both as a drug substance (DS) and a drug product (DP) including the (1) design of the mRNA molecule (nucleotide selection, primary and secondary structures), (2) physical state of the mRNA-LNP complexes, (3) formulation composition and purity of the components, and (4) DS and DP manufacturing processes. Finally, we summarize analytical control strategies to monitor and assure the stability of mRNA-based candidates, and advocate for an integrated analytical and formulation development approach to further improve their storage, transport, and in-use stability profiles