Understanding the relationship between crystal structure, plasticity and compaction behaviour of theophylline, methyl gallate, and their 1 : 1 co-crystal

Abstract

Image reproduced with permission from Abbie TrewinOther articles published in this issue include:Dipyrrin based homo-and hetero-metallic infinite architectures Stéphane A. Baudron, CrystEngComm, 2010, Theophylline and methyl gallate can form a 1 : 1 co-crystal. Their tableting performance follows the order of theophylline > co-crystal [ methyl gallate. While co-crystallization profoundly improves the tabletability of methyl gallate, it significantly deteriorates that of theophylline. This difference in bulk compaction behaviour originates from the dissimilar crystal plasticity and elasticity, which results from unique molecular packing features in the respective crystal lattices. The presence of a three-dimensional hydrogen bonded network gives rise to very low plasticity in the methyl gallate crystal, which leads to its poor tabletability. In contrast, the layers of two-dimensional rigid, hydrogen bonded molecules in the co-crystal improve the crystal plasticity, by facilitating slip with shear that, in turn, enhances tabletability. However, theophylline undergoes plastic deformation more readily when compared to the co-crystal, because the slip layers in theophylline are composed of hydrogen bonded columns, which provide additional flexibility for slip. As a consequence, theophylline crystals have significantly enhanced tabletability.

Overcoming Poor Tabletability of Pharmaceutical Crystals by Surface Modification

“…Since a new crystal must be treated as a new chemical entity, commercialization is likely delayed. Second, only a limited number of solid forms can be made for each drug molecule, and there is no guarantee that the new crystals exhibit satisfactory tableting behavior (19). Moreover, a new crystal form with superior mechanical properties may be associated with other problems, such as poor stability and solubility.…”

Liquid-Assisted Grinding to Prepare a Cocrystal of Adefovir Dipivoxil Thermodynamically Less Stable than Its Neat Phase

“…While the overall shapes of AD raw material (Figure 2a,b) somewhat resembled the AD/GLU crystals, its individual crystals appeared thinner In general, the breakage of particles during milling is related to the maximum fracture energy, Young's modulus, Poisson ratio, hardness as well as initial particle size [17,18]. Fundamentally, these materials properties originate from the intermolecular interactions that govern the crystal structures and determine responses when subject to mechanical stress [14,19]. In the present study, further analysis on the different morphologies of AD cocrystals formed by grinding was hindered by the lack of AD/GLU crystal structure.…”

New Insights into an Old Molecule: Interaction Energies of Theophylline Crystal Forms

“…In addition to these crystal forms, THEO readily forms a range of other co-crystals and 5 is commonly studied as a co-crystal former. [37][38][39][40][41][42] Recently, a new anhydrous form IV has been reported. 43,44 However, reproduction of this form following the published procedure of slurry conversion in methanol failed in our hands.…”