The invention provides therapeutic particulates including a macrolide, such as rapamycin, in solid state crystalline form, having a size of 20μm or less, or 10μm or less. The particulates are formed in one method by preparing a composition with a macrolide and first (e.g., xylene) and second (e.g., an alcohol, acetone, or acetonitrile) solvents. In the composition a maximum solubility for the macrolide that is greater than a maximum solubility of the macrolide dissolved in either the first or second solvent individually. The first and second solvents are then evaporated from the composition to provide the macrolide particulates. In another method, the particulates can be formed by a method including sonication and stirring/evaporation steps, and the particulates can be obtained from a supersaturated solution, formed during the process. Particulates display desirable low polydispersity, and can be used in therapeutic compositions, or can be associated with an implantable or insertable medical device for the treatment of a subject.