Diagram depicting the regeneration phenomenon in a paracetamol crystal post breakage along its cleavage plane.

The crystallization of peptides offers a sustainable and inexpensive alternative to the purification process. In this study, diglycine was crystallised in porous silica, showing the porous templates’ positive yet discriminating effect. The diglycine induction time was reduced by five-fold and three-fold upon crystallising in the presence of silica with pore sizes of 6 nm and 10 nm, respectively. The diglycine induction time had a direct relationship with the silica pore size. The stable form (α-form) of diglycine was crystallised in the presence of porous silica, with the diglycine crystals obtained associated with the silica particles. Further, we studied the mechanical properties of diglycine tablets for their tabletability, compactability, and compressibility. The mechanical properties of the diglycine tablets were similar to those of pure MCC, even with the presence of diglycine crystals in the tablets. The diffusion studies of the tablets using the dialysis membrane presented an extended release of diglycine through the dialysis membrane, confirming that the peptide crystal can be used for oral formulation. Hence, the crystallization of peptides preserved their mechanical and pharmacological properties. More data on different peptides can help us produce oral formulation peptides faster than usual.

Crystalline active pharmaceutical ingredients with comparable size and surface area can demonstrate surface anisotropy induced during crystallization or downstream unit operations such as milling. To the extent that varying surface properties impacts bulk powder properties, the final drug product performance such as stability, dissolution rates, flowability, and dispersibility can be predicted by understanding surface properties such as surface chemistry, energetics, and wettability. Here, we investigate the surface properties of different batches of Odanacatib prepared through either jet milling or fast precipitation from various solvent systems, all of which meet the particle size specification established to ensure equivalent biopharmaceutical performance. This work highlights the use of orthogonal surface techniques such as Inverse Gas Chromatography (IGC), Brunauer–Emmett–Teller (BET) surface area, contact angle, and X-ray Photoelectron Spectroscopy (XPS) to demonstrate the effect of processing history on particle surface properties to explain differences in bulk powder properties.

Solvents play a pivotal role in crystallisation, affecting crystal growth and properties. This study investigates the regeneration behaviour of paracetamol crystals in ethanol, tetrahydrofuran, and acetone using both evaporative and isothermal crystallisation setups, coupled with a custom MATLAB-based edge detection algorithm for facet-specific growth rate measurements. Regeneration was observed in all solvents, with the fastest rate observed in ethanol (0.07 mm h⁻¹), followed by THF (0.03 mm h⁻¹), and acetone (0.02 mm h⁻¹) at a supersaturation ratio of 1.10. In all cases, regeneration was driven by rapid growth of the (0 1 0) facet, restoring crystals to their original shapes. Crystal shape influenced the regeneration time, with a rapid initial phase comprising 8–15% of total regeneration time. Molecular dynamics simulations were utilised to quantify solvent–crystal interactions, showing that not only do the inherent solvent properties play a role but also the solubility of paracetamol significantly affects crystal regeneration.