Designing Lenalidomide Cocrystals with Reduced Solubility for Improved Pulmonary Drug Delivery [dataset]

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 this article, we present a cocrystal of lenalidomide and melamine with reduced solubility which may improve its bioavailability for inhalable formulations for treating pulmonary fibrosis. 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 and a flatter dissolution profile than pure lenalidomide, making it more suitable for inhalable formulation approaches. A preliminary study shows that the cocrystal can be micronised with lactose as a model excipient with particle sizes in the appropriate order of magnitude for use in an inhalable formulation.