A controlled release antibiotic wound protectant gel formulated for use in austere environments

Abstract

Battlefield wounds are at high risk of infection due to gross contamination and delays in evacuation from forward-deployed locations. The aim of this study was to formulate an antibiotic wound gel for application by a field medic in austere environments to protect traumatic wounds from infection during transport. Formulation development was conducted over multiple phases to meet temperature, handling, in vitro elution, and in vivo tissue response requirements. Thermal properties were evaluated by vial inversion, DSC, and syringe expression force in a temperature range of 4–49°C. Handling was evaluated by spreading onto blood-contaminated tissue and irrigation resistance. Controlled antibiotic release was evaluated by a modified USP immersion cell dissolution method. Local tissue effects were evaluated in vivo by subcutaneous implantation in rats for 7 and 28 days. An oleogel composition of cholesterol, hydrogenated castor oil, soybean oil, and glyceryl monocaprylocaprate met the target performance criteria. Peak expression force from a 5 mL syringe at 4°C was 48.3 N, the dropping point temperature was 68°C, and the oleogel formulation could be spread onto blood-contaminated tissue and resisted aqueous irrigation. The formulation demonstrated sustained release of tobramycin in PBS at 32°C for 5 days. Implantation in a rat dorsal pocket demonstrated a slight tissue reaction after 7 days with minimal to no reaction after 28 days, comparable to a commercial hemostat control. Material resorption was evident after 28 days. The formulation met target characteristics and is appropriate for further evaluation in a large animal contaminated blast wound model.