Drug release profiles from and degradation of a novel biodegradable polymer, 2,2-bis(2-oxazoline) linked poly(epsilon -caprolactone).

In the present study, poly (epsilon -caprolactone) (PCL) was modified by introducing oxamide groups into PCL (PCL-O). The degradation (decrease in molecular weight) and erosion (weight loss) of PCL and PCL-O films were studied in PBS (pH 7.4, USP XXIV, 37 degrees C, 26 weeks incubation). The release rates of guaifenesin (M(w) 198.2), griseofulvin (M(w) 352.8), timolol (M(w) 332.4), sodium salicylate (M(w) 160.1) and FITC-dextran (M(w) 4400) from PCL and PCL-O preparations (solvent cast films, compression-molded plates, midi injection-molded rods and microparticles) were examined in PBS (pH 7.4, 37 degrees C). The degradation rate of PCL-O film was faster than that of PCL film while no erosion was observed for either film. When compared to the corresponding drug release from PCL films, the release rates of low molecular weight drugs (M(w)< or =352.8) from PCL-O films were comparable, their releases from both films following closely square-root-of-time kinetics. These results indicate that the oxamide groups had no substantial effect on the release of the low molecular weight drugs. The exception was sodium salicylate which was released faster from PCL-O film. However, FITC-dextran release was notably faster from PCL-O microparticles than from those made of PCL. FITC-dextran release was a combination of diffusion and polymer degradation and thus, the faster degradation of PCL-O enhanced the release of FITC-dextran. In conclusion, the effects of the oxamide groups on drug release profiles were dependent on the drug release mechanisms.

Degradation of and drug release from a novel 2,2-bis(2-oxazoline) linked poly(lactic acid) polymer.

The degradation rate of poly(lactic acid) (PLA) is typically modified by copolymerization of the glycolide with lactide. In the present study, the degradation rate of PDLLA was modified by a novel linking of PLA with 2,2'-bis(2-oxazoline). This modification resulted in formation of a more rapidly degrading poly(ester amide) (PEA) for controlled drug release. The hydrolytic degradation of PDLLA and PEA films was studied in PBS (pH 7.4, USP XXIV, 37 degrees C); the resulting decrease in molecular weight was determined by size exclusion chromatography and the weight loss of films was measured. Drug releases of guaifenesin (mw 198.2), timolol (mw 332.4), sodium salicylate (mw 160.1) and FITC-dextran (mw 4400) from PDLLA and PEA films and microspheres were examined in PBS (pH 7.4, 37 degrees C). The degradation rate of PEA was substantially greater than that of PDLLA. The release profiles of all small model drugs (mw <332.4) from PDLLA films were biphasic or triphasic, while the release profiles of small model drugs from PEA films varied extensively. Due to the faster weight loss of PEA, FITC-dextran (mw 4400) was released substantially more rapidly from PEA microspheres than from PDLLA microspheres. In conclusion, all model drugs, except guaifenesin, were released faster from PEA preparations than from PDLLA preparations.