Depot formulations for on-demand tamper- and diversion-proof delivery of opioids

Summary Opioids are commonly prescribed for a variety of acute and chronic pain states. Unfortunately, prescribed opioids can be tampered with or diverted, both of which can have severe consequences (e.g., lethal overdose). Tamper-resistant formulations have had limited success, and cannot prevent diversion of drugs. Injectable formulations that can deposit an extended

course of treatment in the body would make diversion nearly impossible once administered, but most, if stolen, can still be tampered with (and the opioid extracted) by relatively simple means. Importantly, once administered to patients, they deliver drugs at a rate that does not change with the varying needs of the patient. They are therefore unusable for acute pain: if opioids were

continuously released at a rate adequate for acute pain, patients would be narcotized for extended periods. Here, we propose to develop depot formulations made of polymers which are attached covalently to opioids by photolabile linkers. The depots would be injected subcutaneously by healthcare providers, for example, prior to discharge after a procedure. The

covalent linkers would render the depots difficult to tamper with, as the drug cannot be easily removed from stolen devices by simple dissolution in organic solvents. Moreover, having been injected into the body the formulations could not be diverted from patients. The covalent bonding prevents the drug from being active even after injection, and the drug is only released

by irradiation – not polymer degradation. However, since the bonds are photolabile, the patient would be able to release the drug with a simple handheld or wearable light source. This approach would allow patients to determine the timing, intensity, and duration of analgesia throughout the postoperative period.