Drug delivery devices (e.g., polymeric vaginal rings) and related methods of manufacture and treatment are disclosed herein. In some embodiments, a manufacturing process for drug delivery devices is disclosed that includes a compounding extrusion process and an injection molding process. The various manufacturing parameters associated with these processes can be optimized to produce a drug delivery device with a favorable release profile and other characteristics. In particular, reducing the energy introduced into the system during manufacture can unexpectedly result in drug delivery devices with improved release profiles, especially in the case of large molecule drugs or in devices with a relatively low drug loading or drug particle size.