Particle Engineering: Fundamentals of Particle Formation and Crystal Growth

Abstract

The engineering of particles with customized properties optimized for dosage form manufacture (tablet, capsule, ointment, etc.) has long been a goal of the pharmaceutical industry. Particles can be designed through modification in the size, morphology, and packing arrangement of the solids. The most common approach in achieving this is through crystallization. In this bottom-up process, the two main steps, nucleation and crystal growth, both play a decisive role in shaping the quality of the final crystalline product. In this review, the role of nucleation and crystal growth in controlling particle properties is discussed, and examples are provided that demonstrate the variation in solid-state properties as a function of size, habit (morphology), and internal structure of the particles. In addition, the role of particle properties in product performance and dosage form development of pharmaceuticals is also discussed.

Concomitant Polymorphism in Confined Environment

“…This has significant implications in the pharmaceutical industry as properties affected by different polymorphic forms include melting point, density, hardness, hygroscopicity, dissolution rate and solubility, which can in turn impact the process acceptability and bioavailability of a drug substance (3). In this regard, the selection of a desired solid state form for processing and the final product is one of the vital steps in drug development (4).…”

Highly Efficient Patterning of Organic Single‐Crystal Transistors from the Solution Phase

“…A similar approach was previously chosen to grow crystals of glycine on patterned gold surfaces from droplets of a highly undersaturated aqueous solution. [17,18] A difficulty with small organic semiconductor molecules is their low solubility in organic solvents, which is typically of the order of a few mg mL À1 ($30 times less than glycine in water). Therefore, patterning an amount of the organic semiconductor sufficient to grow a crystal that is large enough to bridge the electrodes requires solutions that are close to saturation.…”

Highly Unusual Triangular Crystals of Theophylline: The Influence of Solvent on the Growth Rates of Polar Crystal Faces

“…[12][13][14] For example, in many applications the shape and size of particles must be carefully controlled to ensure that product performance is consistent from batch to batch. 12,[14][15][16] Furthermore, while the process of generating a desired particle size and morphology profile in a batch of material has traditionally been performed post crystallization through techniques such as milling and micronisation, 17,18 it is more desirable to gain sufficient control of the crystallization step such that crystals with optimum characteristics are grown directly. [18][19][20] For these reasons, focus has recently been directed to gaining further control and understanding of crystallization processes.…”

“…[26][27][28][29] This is important because the various crystal forms a compound may adopt can have very different properties. 17,30,31 While it is still usually impossible to say 'a priori' which crystal form will result from a given set of crystallization conditions, 32 notable advances have been made in recent years in the prediction of aspects of polymorphic behaviour. [33][34][35][36] For example, using crystal structure prediction it is now routinely possible to computationally generate plausible crystal structures for a simple organic compound and determine which is likely to be the most stable form on the basis of lattice energy calculations.…”