Crystal Engineering and Structures of Pharmaceutical Molecules

Dear Colleagues,

Pharmaceutical drugs are primarily formulated in crystalline solid forms due to the superior purity, stability and marketability as tablets, which are easy to orally consume. Solid forms can exist as polymorphs, salts, cocrystals, hydrates, solvates, solid solutions, eutectics, amorphous phases, etc. The solid form is highly important in adjusting a drug’s properties, impacting variables such as the solubility, permeability, bioavailability, tabletability and physical/chemical stability. Controlling solid forms via nucleation and adjusting pharmaceutically relevant properties are highly challenging and difficult to predict areas of research. Therefore, designing next-generation pharmaceutical cocrystals, including drug–drug binary/ternary cocrystals and eutectic solid forms using a crystal engineering approach, may be a vital tool in solving problems concerning the tunability and optimization of desirable properties in pharmaceutical solid forms.

Currently, nine drug-based cocrystals are commercially available, with many more on the pipeline in drug development stages. Here, we chose the biopharmaceutics classification system (BCS) classes II, III and IV with either solubility/permeability problems, and their transformation into the BCS class I, with improved solubility and permeability using a cocrystal engineering approach. One example of the challenges faced is that many of the drugs are of a brittle nature in their native forms and need an excipient as a binder to create compressible tablets. A crystal engineering approach can be utilized to create compressible tablets in the native form itself. In addition, approximately 15% of drugs are labile in acidic/basic media, thus, requiring special attention from the crystal engineer to provide a remedy and improve their bioavailability. In conclusion, solid-state chemistry has an important role in tuning varieties of solid forms that alter the crystal packing arrangement and, hence, drug properties.

In this Special Issue, we would like to highlight recent developments in altering drug properties through the engineering of solid forms. Themes to be addressed include, but are not limited to:

 • Novel polymorphs, hydrates and solvates of novel or commercialized drugs;
 • Pharmaceutical cocrystals and salts in tuning drug properties;
 • Drug–drug binary/ternary or higher-order cocrystals with improved properties, including clinical efficacy;
 • Structure–property correlation among novel solid forms;
 • Novel drug eutectic solid forms and solid solutions;
 • Crystal structure solution from high-resolution PXRD.

Dr. Palash Sanphui
Guest Editor

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• crystal engineering
• pharmaceutical polymorphs
• cocrystals
• salts
• eutectics
• drug properties