Release mechanisms of urinary tract antibiotics when mixed with bioabsorbable polyesters

In depth knowledge of the thermal properties of drugs is particularly important when they are designed for incorporation into a thermoplastic polymer matrix. In this paper a representative set of Urinary Tract Infection (UTI) antibiotics were studied using thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC), and then blended via solvent-casting method with poly(D,L-lactide-co-ε-caprolactone). Of these, amoxicillin, cefdinir, levofloxacin and norfloxacin showed a co-continuous morphology with the polyester, whereas blends with ciprofloxacin, nitrofurantoin and tobramycin resulted in two immiscible phases. E. coli susceptibility results showed that the activity of these antibiotics was not affected by the interactions with the polymer matrix. The presence of the drug did not change the hydrolytic degradation kinetics of this fully amorphous polyester (K_Mw of ~0.050 days^-1). However, the release profiles from the long-term studies (105 days) with a 10 or 30% of antibiotic-loaded films were quite different. While water was able to penetrate the polymer matrix and elute the entire levofloxacin content in the first 8 h, the burst release of cefdinir reached a value under 75%. A more interesting profile was obtained with nitrofurantoin, suggesting that a lengthy treatment is achievable. <30% of the drug was burst released, ~55% eluted by diffusion up to day 42 and the rest driven by the weight loss of the bioabsorbable polyester.