Enhancing Pharma Processes

One of the main challenges in pharmaceutical research and quality control, besides funding, is time. Significant time can be lost in unambiguously characterizing new compounds, including understanding their molecular structure and crystal form. This process can be hindered if compounds are difficult to crystallize, require scaling up small amounts, purification, or characterization of polymorphs. Traditional methods like NMR, FTIR, and solid-state powder measurements may not provide complete structural information (e.g., absolute configuration) or are challenging to perform with limited sample amounts or impure bulk materials.

Single crystal X-ray crystallography involves directing a monochromatic and focused X-ray beam onto a single crystal. The interaction of the X-rays with the electrons in the crystal produces discrete reflections, which are recorded on a detector. By rotating the crystal and recording these reflections, the data is mathematically processed using Fourier transform to generate an electron density map. The maxima in this map reveal the positions of atoms, allowing for the determination of the molecular structure and crystal packing. The main limitations of X-ray crystallography relate to crystal quality and size. The tightness of molecular packing and the size of the crystal affect the quality of the diffraction data. X-ray crystallography typically requires crystals that are at least one micron in dimension. Below this size, the interaction of X-rays is too weak for effective analysis, necessitating alternative methods.

Electron diffraction is preferred when X-ray crystallography fails, particularly when dealing with very small crystals or crystalline powders. The interaction of electrons with crystalline matter is much stronger than that of X-ray photons, by several orders of magnitude. This allows electron diffraction to analyze submicron particles, even those with dimensions around 50 nanometers or less. Consequently, electron diffraction can be performed on crystalline powders, eliminating the need to grow larger single crystals. It requires only tiny amounts of sample, making it suitable for analyzing the very first solids obtained during synthesis when traditional methods might not have enough material.

Stock solutions are concentrated solutions of common reagents prepared in advance for laboratory experiments. They are essential for many lab settings and can be categorized into types like salt solutions, buffers, precipitants, and prepared reagent solutions (which may contain multiple components). Having stock solutions readily available is important because they are often needed in multiple steps of an experiment. Preparing them ahead of time saves valuable time that would otherwise be spent mixing solutions from scratch for each experiment. This also helps reduce errors and ensures consistency across experiments, which is critical for reliable results.

Liquid handling instruments can significantly enhance research efficiency and accuracy. However, their performance is highly dependent on a consistent and adequate supply of stock solutions. Without proper stock solution management, inadequate or inconsistent supply can lead to errors in experiments, compromise data integrity, and potentially cause downstream issues. Therefore, effective management of stock solutions is crucial for maximizing the benefits of using liquid handling instrumentation, ensuring smooth workflow, and avoiding delays in high-throughput laboratories. Keeping accurate records of stock solution batches, even without automated systems, is important to track usage and maintain inventory.