Feasibility of poly (ϵ-caprolactone-co-DL-lactide) as a biodegradable material for in situ forming implants: evaluation of drug release and in vivo degradation.

The purpose of this study was to evaluate the technical feasibility of poly (ϵ-caprolactone-co-DL-lactide), P (CL/DL-LA), for injectable in situ forming implants (ISFI). The ISFI was prepared by dissolving P (CL/DL-LA) in N-methyl-2-pyrrolidone (NMP), and Testosterone undecanoate (TU) was used as model drug. The effect of various polymer concentrations, molecular weights (Mws) and drug loads on the drug release from the TU-loaded ISFI systems was investigated in vitro. The release of TU-loaded ISFI was also evaluated in rats. In addition, a subcutaneous rabbit model was used to evaluate the degradation and foreign-body reaction of P (CL/DL-LA) ISFI. The use of higher concentration of P (CL/DL-LA) with higher molecule weight and larger CL:DL-LA monomer ratio for the TU-loaded ISFI gave a slower drug release. The ISFI of 80/20 P (CL/DL-LA) (Mw 61 753):NMP 20:80 with 16% TU formulation increased serum testosterone levels in rats over a period of three months. The in vivo degradation and biocompatibility study of ISFI shows that P (CL/DL-LA) degrades by a process of bulk degradation and that the foreign-body reaction of this biomaterial is relatively mild. In summary, our investigations demonstrate that in situ parenteral drug delivery systems can be obtained from P (CL/DL-LA) solutions.