Various formulations (to be used in the form of a single-segment or multi-segment transdermal patch) of bioactive compounds for pain management are described/disclosed. The multi-segmented transdermal patch can include one or more compatible bioactive compounds in each segment. Furthermore, formulations may include silk fibroin and/or microemulsion/nanoemulsion of bioactive compounds and/or microencapsulation/nanoencapsulation of bioactive compounds.