Influence of Tween 80 on Crystal Morphology, Particle Size, and Dissolution in Pharmaceutical Crystallization

Abstract Additives play a pivotal role in enhancing the pharmaceutical crystallization by improving the properties of active pharmaceutical ingredients (APIs), such as crystal habit, crystal shape, particle size, and dissolution rates. This review explores the impact of Tween 80, a non‐ionic surfactant, on the crystallization behavior of various APIs, focusing on its ability to optimize drug formulations. The study highlights that Tween 80 significantly influences crystal morphology, transforming irregular or needle‐like crystals into more compact, uniform forms, improving flowability and tabletability. Additionally, Tween 80 effectively reduces particle size, enhancing the rate of dissolution of poorly soluble APIs, thereby improving bioavailability. When crystallized in the presence of Tween 80, most of the compounds do not exhibit any polymorphic transition, maintaining their original crystal forms. Being non‐ionic in nature, Tween 80 doesn't produce the strongest of the interaction with the functionalities on the crystal facets, which results in it being unable to drastically affect morphology, growth rate and dissolution profile, in comparison to other additives like sodium lauryl sulphate (SLS), Polyvinylpyrrolidone (PVP) K‐30, Polyethylene glycol (PEG) 4000, etc. Furthermore, the paper also highlights the importance of optimizing additive concentrations and explores spherical crystallization technique of quasi‐emulsion solvent diffusion (QESD) for its role in forming spherical agglomerates, which display improved powder properties and processability. Computational studies utilizing molecular dynamics simulations, BFDH (Bravais‐Fridel, Donnay‐Harker) morphology predictions, and attachment energy models offered valuable insights into the molecular‐level interactions between Tween 80 and APIs, clarifying its role in shaping crystal morphology and controlling growth patterns.