Designing lenalidomide cocrystals with an extended-release profile for improved pulmonary drug delivery†

Lenalidomide is a poorly soluble immunomodulatory drug that has been the subject of several cocrystal studies aiming to improve oral bioavailability by enhancing solubility. In contrast, for application in pulmonary fibrosis, reduced solubility may extend the retention time and reduce potential side effects of inhalable formulations. In this article, we present a proof-of-principle study on a low-solubility cocrystal of lenalidomide and melamine. The structure of the hydrated cocrystal was determined by single crystal X-ray diffraction and revealed a 3-dimensional hydrogen-bonding network between lenalidomide, melamine and channel-included solvent. The cocrystal has a lower maximum solubility than pure lenalidomide, making it more suitable for inhalable formulation approaches. A preliminary study shows that the cocrystal can be micronized with lactose as a model excipient with particle sizes in the appropriate order of magnitude for use in an inhalable formulation.