Cocrystals can be used as an alternative approach based on crystal engineering to enhance specific physicochemical and biopharmaceutical properties of active pharmaceutical ingredients (APIs) when the approaches to salt or polymorph formation do not meet the expected targets. In this article, an overview of pharmaceutical cocrystals will be presented, with an emphasis on the intermolecular interactions in cocrystals and the methods for their preparation. Furthermore, cocrystals of direct pharmaceutical interest, along with their in vitro properties and available in vivo data and characterization techniques are discussed, highlighting the potential of cocrystals as an attractive route for drug development.

The amorphous solid state offers an improved apparent solubility and dissolution rate. However, due to thermodynamic instability and recrystallization tendencies during processing, storage and dissolution, their potential application is limited. For this reason, the production of amorphous drugs with adequate stability remains a major challenge and formulation strategies based on solid molecular dispersions are being exploited. Co-amorphous systems are a new formulation approach where the amorphous drug is stabilized through strong intermolecular interactions by a low molecular co-former. This review covers several topics applicable to co-amorphous drug delivery systems. In particular, it describes recent advances in the co-amorphous composition, preparation and solid-state characterization, as well as improvements of dissolution performance and absorption are detailed. Examples of drug-drug, drug-carboxylic acid and drug-amino acid co-amorphous dispersions interacting via hydrogen bonding, π−π interactions and ionic forces, are presented together with corresponding final dosage forms.

Nanoparticle-based therapeutics have been used in pulmonary formulations to enhance delivery of poorly water-soluble drugs, protect drugs against degradation and achieve modified release and drug targeting. This review focuses on the use of spray drying as a solidification technique to produce microparticles containing nanoparticles (i.e., nanoparticle (NP) agglomerates) with suitable properties as dry powders for inhalation. The review covers the general aspects of pulmonary drug delivery with emphasis on nanoparticle-based dry powders for inhalation and the principles of spray drying as a method for the conversion of nanosuspensions to microparticles. The production and therapeutic applications of the following types of NP agglomerates are presented: nanoporous microparticles, nanocrystalline agglomerates, lipid-based and polymeric formulations. The use of alternative spray-drying techniques, namely nano spray drying, and supercritical CO₂-assisted spray drying is also discussed as a way to produce inhalable NP agglomerates.