S.-J. Liu 1 *, C.-H. Tsai 1 , S.-S. Lin 2 , S. W.-N. Ueng 2 1) Polymer Rheology and Processing Laboratory, Department of Mechanical Engineering, Chang Gung University, Tao-Yuan, Taiwan 2) Department of Orthopedic Surgery, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan Processing of Biodegradable Polymer Composites as A Drug Delivery System in Vitro This report explores the alternative of processing biodegrad- able polymer-antibiotic composites as a long-term drug release. Polymer-antibiotic composite beads were manufac- tured by a compression-sintering technique. An elution method was employed to characterize the release rate of antibiotic over a 35-day period at 37  C. Biodegradable polymer composites released high concentrations of anti- biotic (well above the breakpoint sensitivity concentration) in vitro for the period of time needed to treat bone infection; i.e. 4 to 6 weeks. By changing the processing variables, one is able to control the release rate of the beads. This provides advantages of meeting the speci®c antibiotic requirement for patients with various surgical infections. 1 Introduction Orthopedic infection is dif®cult to treat and eradicate [1]. Delivering an effective antibiotic at suf®ciently high concen- trations to the area of infection in combination with surgery is a recognized treatment for bone infection [2 to 3]. It is usually performed with the use of polymethylmethacrylate (PMMA) bone cement composites in combination with standard treat- ments for bone infection. The success rate varies from 40 % to 90 %. The disadvantages associated with using the PMMA composites include a necessary secondary surgery to remove the composites and a less than optimal antibiotic elution pro®le since only 50 % of the antibiotic is eluted from the composite after four weeks [4]. Antibioticcompositesmadeoutofbiodegradablepolymers have advantages over conventional polymethylmethacrylate composites and intravenous antibiotics in four ways. First, biodegradable composites provide bactericidal concentrations of antibiotics for the prolonged time needed to completely treat the particular orthopedic infection. Second, variable biodegradability from weeks to years may allow many types of infections to be treated. Third, because the biodegradable beads dissolve, there is no need for surgical removal; and fourth, because the biodegradable composites dissolve slowly, the soft tissue or bone defect slowly will ®ll with tissue, so there is no need for reconstruction. Recent investigations have explored the use of antibiotics incorporated biodegradable materials for potential use in the treatment of bone infection [5]. This current paper explores the alternative of processing biodegradable polymer [6] as antibiotic composites for a long- term drug release. In comparison with other investigators [7 to 13], we proposed a compression-sintering processing techni- que to manufacture polymer-antibiotic composites of various sizes. An elution method and an HPLC assay [5] were used to evaluate the release characteristics of the antibiotic from the composites. 2 Experimental Procedure Antibiotics-polymer composites were fabricated in this study. The biodegradable polymer used was poly(D,L)-lactide-co- glycolide with a ratio of 50 : 50 and an molecular weight of 5,000(BoeringerIngelheimKG,Germany).Itwasavailablein powder form with particle size ranges from 100 to 200 mm.A DuPont model TA-2000 differential scanning calorimeter was used to characterize the thermal properties of the polymer. The measured result in Fig. 1 shows that the polymer's melting temperature is about 45  C. The antibiotic used is vancomycin powder with a particle size of 100± 200 mm (Abott Lab., U.S.A.). To manufacture the composites, the polymer and vanco- mycin was pre-mixed by a lab scale dry mixer. The polymer to vancomycin weight ratio used was 5. The mixture was compressedintobeadsofdifferentdiameters(5,8and10mm) by a mold shown schematically in Fig. 2. The compressed beads with the mold were then placed in an oven for sintering [14]. The sintering temperature was set at 55  C, which was higher than polymers' melting point, but low enough to avoid * Mail address: Prof. Dr. S.-J. Liu, Dept. of Mech. Eng., Chang Gung University, 259 Wen-Hwa 1st Rd., Kwei-Shan, Tao-Yuan 333, Taiwan R.O.C. 322 # Hanser Publishers, Munich Intern. Polymer Processing XIV (1999) 4 BIOMEDICAL ENGINEERING IPP 1999.14:322-325. by RMIT SWANSTON LIBRARY on October 31, 2018. For personal use only.