The goal of this Phase 1 - Phase 2 fast track project is to develop a novel, sustained release dosage form of analgesic that will alleviate post-surgical pain at the site of need for time periods ranging from several days to two weeks. Pain control has been increasingly recognized as an aspect of patient care that is given insufficient attention, and various governmental agencies have announced initiatives to heighten awareness of this problem. Much of the pain experienced by patients emanates from their surgical incisions. This pain inhibits their movement and lengthens hospital stay. The proposed product, containing polymer and NSAID, will be left in the surgical wound just before the physician sutures it closed, and it will deliver 7-14 days' dose of NSAID to injured tissue. NSAIDs are among the most commonly prescribed medications to treat pain. In sufficient doses, they can be as effective as opiates in relieving many types of pain. However, NSAID use can be associated with significant dose-dependent gastric and renal complications, as well as platelet antiaggregative effects that may be undesirable in some clinical situations. Specific local delivery of NSAID directly to the target, with limited systemic circulation, could avoid such toxicity and enhance efficacy of the medicine. Previous preclinical and clinical studies utilizing particulated formulations of pain relieving medications such as anesthetics have resulted in negative tissue reactions as well as inadequate dosage for complete pain relief. A preliminary pre-clinical study has demonstrated the efficacy of these sustained, locally acting pain relievers in relieving incisional pain in the paws of rats. Further refinement of both the product formulation, as well as the duration of action of the drug, is required before it is ready for clinical testing. This Phase I grant will focus upon the optimization of particle shape, polymer carrier chemistry, and dosage requirements to alleviate many of the previously noted issues. The effect of polymer molecular weight, drug loading, particle size and shape, pH of the surrounding media will be studied. At the end of this phase 1 study, a product ready for preclinical testing would have been defined.
