Crystallization is an important separation and particle formation technique in the manufacture of high-value-added products. During crystallization, many physicochemical characteristics of the substance are established. Such characteristics include crystal polymorph, shape and size, chemical purity and stability, reactivity, and electrical and magnetic properties. However, control over the physical form of crystalline materials has remained poor, due mainly to an inadequate understanding of the basic growth and dissolution mechanisms, as well as of the influence of impurities, additives, and solvents on the growth rate of individual crystal faces. Crystal growth is a surface-controlled phenomenon in which solute molecules are incorporated into surface lattice sites to yield the bulk long-range order that characterizes crystalline materials. In this article, we describe some recent advances in crystal morphology engineering, with a special focus on a new mechanistic model for spiral growth. These mechanistic ideas are simple enough that they can be made to work and accurate enough that they are useful.

Recently, a general mechanistic spiral growth model, including a kink rate expression that enables crystal morphology prediction for all kinds of organic molecules (both centric and noncentric), was developed. However, we have discovered that the kink rate model for the step velocity in solution growth is inconsistent with the attachment and detachment rate expressions for noncentric growth units at kink sites, so these expressions are revisited to make them selfconsistent. Here, we derive a new expression for the kink rate for noncentrosymmetric organic molecules, which correctly accounts for the effect of solvent molecules on growth kinetics. We also generalize the kink rate model to consider other species such as additives. Using the spiral growth model with the improved kink rate expression, we have studied the steady state morphology of paracetamol crystals at low supersaturation to understand the morphology transition induced by the solvent effect and compared our predictions with experimental measurements. The model is able to capture the variation in the shape of paracetamol crystals grown from different solvents with reasonable accuracy.

Growth shapes of inorganic crystalline solids govern material properties such as catalytic activity and selectivity, solar cell efficiency, and so forth. A systematic understanding of the crystal growth process and the solid‐state interactions within inorganic crystals should help to engineer crystal shapes. A general model that identifies periodic bond chains in inorganic crystals while accounting for the long‐range electrostatic interactions is presented. The variation in the electronic structure and the partial charges of growth units on the inorganic crystal surfaces has been captured using the bond valence model. The electrostatic interaction energies in the kink sites of inorganic crystals were calculated using a space partitioning method that is computationally efficient. This model provides a quantitative explanation for the asymmetric growth spirals formed on the (101¯4) surface of calcite. This methodology for studying solid‐state interactions can be used with a mechanistic growth model to predict the morphology of a wide variety of inorganic crystals. © 2014 American Institute of Chemical Engineers AIChE J, 60: 3707–3719, 2014

Inorganic crystals grown from solution find wide application. A mechanistic growth model based on the spiral growth mechanism that operates at low supersaturation on inorganic crystal surfaces is presented. The long-range electrostatic interactions on inorganic crystal surfaces are captured by methods developed in our previous article (Dandekar and Doherty, AIChE J., in press). The interactions of kink site growth units with the solvent molecules partially determine the growth kinetics. Relevant experimental parameters are systematically accounted for in the expression for the kink incorporation rate along step edges on the crystal surfaces. The growth model accurately predicts the asymmetric growth spirals on the ð10 14Þ surface of calcite crystals. The effect of supersaturation and ionic activity ratio on the step velocities of the acute and obtuse spiral edges is also correctly captured. This model can be used to predict the shapes of solution grown inorganic crystals and to engineer the growth process to design inorganic solids with functionally desirable shapes.

Model predictions agree well with measurements of total and pulmonary lung deposition for particles of 10 nm to 10 μm, with earlier models incorporating moving boundaries and aerosol dynamics, and with the reported regional lung deposition of inhaled dry powder insulin. To simulate medical inhalation, the model was run with inhalation times from 2-6 sec and breath hold from 0-10 sec. A high and relatively invariant pulmonary deposition fraction between 70 and 95% was predicted for a broad nanoparticle size range (50-200 nm) for inhalation cycles with breathing rate between 500 and 2000 cm(3) sec(-1) and breath hold of 5-10 sec. Thus, nanoparticles may be able to deliver consistent lung doses, over modest breath hold periods, even with intrapatient variability in breathing rate. A linearized nomogram was provided as a heuristic for design of nanoparticle drug matrices to target the pulmonary lung.

Real-time atomic force microscopy provides insights into complex processes associated with crystal growth. [Also see Report by Lupulescu and Rimer ]

Crystal habit of drug molecules can have significant influence on the processing and performance of pharmaceutical products. During the development of Trilipix, a pharmaceutical product used for the treatment of mixed dyslipidemia, several crystal habits were observed for the active ingredient choline fenofibrate. The dissolution and performance of the drug product were not impacted by changes in crystal habit of the active ingredient due to high solubility of the drug. However, the formulation process was impacted by variations in crystal habit of the active ingredient, requiring robust control of the crystal habit. The crystal habit was greatly influenced by supersaturation during crystallization from a mixed solvent system comprising methanol and isopropanol. In addition to supersaturation, trace levels of a polymeric impurity in the starting material fenofibrate had a detrimental effect on the crystal habit. This article discusses the effects of these factors on the crystal habit of choline fenofibrate and the design of a crystallization process to deliver the target crystal habit, most suited to the formulation process. The article also provides preliminary mechanistic insights into the crystal habit of this organic salt using an extension of the spiral growth model for morphology prediction of organic molecular crystals. An attempt is made to explain the effect of supersaturation and impurity on the crystal habit of choline fenofibrate using the concepts of stability of surfaces, building units, periodic bond chain theory, and the spiral growth model.

T he original published paper did not include a crystallographic information file (CIF) as described in the Supporting Information. This file is included in this addition/ correction. ■ ASSOCIATED CONTENT* S Supporting Information Crystallographic information file. This material is available free of charge via the Internet at http://pubs.acs.org.