Pharmaceutical-derived microplastics: sources, detection, and toxicological implications for patient safety.

Pharmaceutical products and the polymers used to manufacture them are often overlooked sources of microplastic (MP) exposure, with real implications for patient safety and the environment. Contamination arises from PE, PP, and PET packaging; elastomeric stoppers; plasticized PVC in IV bags and administration sets; excipients; and manufacturing-related contamination. The route of administration is important because injectables and IV infusions can deliver particles directly into systemic circulation, bypassing barriers that limit exposure via oral or topical routes.This review elaborates on leaching pathways driven by physical, chemical, interactive, and aging processes, as well as analytical methods, including optical and scanning electron microscopy, FTIR and Raman spectroscopy, and pyrolysis GC/MS, and emerging single-particle techniques differ in detection limits and face challenges from matrix interference and procedural contamination. Toxicological studies indicate that particle size, shape, and surface chemistry influence oxidative stress, and inflammatory responses. Nanoplastics are of particular concern due to their ability to cross biological barriers and enter cells, yet data on pharmaceutical-derived MPs and co-leaching additives (phthalate plasticizers, antioxidants, elastomer curing agents, residual catalysts) remain limited.Current pharmacopeial standards (USP <788>, <787>) classify particles only by size, ignoring polymer identity and excluding the submicron range. Extractables-and-leachables frameworks (USP <1663>, <1664>, ICH Q3E) address dissolved chemicals rather than intact particulate matter, leaving MPs insufficiently addressed by current regulations. Closing it requires packaging designed to shed less material from the outset, toxicokinetic data from real biological samples rather than models, longer-term in vivo and epidemiological studies, and contamination-free analytical workflows.