Surface-induced crystallization of pharmaceuticals and biopharmaceuticals: A review

Despite the wide occurrence of crystallization in the pharmaceutical industry, deep understanding and fine control of the process remain a tricky issue. Nevertheless, the successful manufacturing of finished pharmaceutical products, as well as the structural determination of biopharmaceuticals, depend on the size, form, shape and purity of the crystals. The ability of substrates with precise chemistry and topological features to induce nucleation has been thoroughly assessed during the recent years. This paper reviews the major advances and discoveries in controlling small molecule drug and protein crystallization by means of engineered surfaces. By designing superficial properties and morphology, it has been possible to tune the polymorph outcome, shorten the nucleation induction time, impose specific crystal shapes, control the crystal size and carry out crystallization at very low supersaturation levels. Such achievements underline the potential of surface-induced crystallization to provide an ideal platform for the study of the nucleation process and gain control over its stochastic nature.