Nucleation, the initial process in vapor condensation, crystal nucleation, melting, and boiling, is the localized emergence of a distinct thermodynamic phase at the nanoscale that macroscopically grows in size with the attachment of growth units. These phase changes are the result of atomistic events driven by thermal fluctuations. The occurrence of atomistic level events with the length scales on the order of 10 −10 m and time scales of 10 −13 S equivalent to the vibrational frequency of atoms makes the nucleation a very complicated phenomenon to study. Even though abundant literature is available about fundamental aspects of nucleation, the knowledge on these phenomena is far from complete. The classical pathway to nucleation which was once considered to have general applicability to all nucleating systems is gradually giving way to a nonclassical pathway which is now considered as a dominating mechanism in solution crystallization and other systems. In this review, an attempt is made to compare underlying physical principles involved in various nucleating systems and their theoretical treatment based on classical nucleation theory, and other important theories such as a density functional approach and diffuse interface theory. The limitations of classical theory, the gradual evolution of a nonclassical two-step pathway to nucleation, and the questions that have to be addressed in the future are discussed systematically.

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The thrust to adopt sustainable greener technologies in chemical and pharmaceutical process industries has been growing since last two decades due to the intense usage of volatile organic solvents from synthesis to purification stages. Hence, the objective of the present study is to analyze the feasibility of replacement of the organic solvent used in the purification of an active pharmaceutical ingredient (API) in a pharmaceutical context. From this perspective, the crystallization of an API-ibuprofen using ethyl lactate as an alternate green solvent is explored for the first time in the present study. Ethyl lactate belongs to the family of lactate esters, which is 100% biodegradable in nature. The feasibility of crystallization of ibuprofen is analyzed and a methodology is developed to crystallize the same. In addition, the kinetic parameters for the unseeded batch cooling crystallization of ibuprofen grown in 50% aqueous ethyl lactate have been estimated. A model of the crystallizer is constructed based on first-principles and a nonlinear optimization based methodology is used for extracting the kinetics. The results show that ibuprofen can be crystallized from aqueous ethyl lactate and the kinetic parameters are reported for the region where the system does not pass through two phase separation.