MANUFACTURE OF CONTROLLED DRUG DELIVERY DEVICE OF POLYCAPROLACTONE BY SELECTIVE LASER SINTERING ABSTRACT

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1 MANUFACTURE OF CONTROLLED DRUG DELIVERY DEVICE OF POLYCAPROLACTONE BY SELECTIVE LASER SINTERING P. Klauss 1*, G. V. Salmoria 1, M. Souza 1, L. A. Kanis 2 1* Laboratory CIMJECT, Federal University of Santa Catarina (UFSC), , Florianópolis, Brasil pklauss@cimject.ufsc.br; 1 Laboratory CIMJECT, Federal University of Santa Catarina; 2 Grupo de Tecnologia Farmacêutica - TECFARMA, UNISUL, , Tubarão, Brasil. ABSTRACT Polycaprolactone specimens were built by selective laser sintering under different energy densities values of the laser beam. The effects of energy density, ranging from 0.09 to 0.27 J/mm 2 were analyzed by mechanical properties and morphology of specimens sintered. The polycaprolactone samples sintered with higher density energy value results in a better fusion of the powder presented highest degree of sintering and pore size lower than samples sintered with lower energy density value. The values of the flexural modulus and strength increased with higher values of energy density, because the degree of sintering and the number of necks by area. This work showed is feasible the specimens manufacture of the polycaprolactone by SLS for applications in drug delivery devices. Key-words: selective laser sintering, polycaprolactone, drug delivery devices INTRODUCTION Selective Laser Sintering (SLS) is a Rapid Prototyping technique that creates 3D objects by the sinter of powder materials using infrared laser beams (1-9). Williams et al. (2005) investigated the built of the porous PCL scaffolds fabricated via selective laser sintering (SLS) and that show great potential for replacement of skeletal tissue. The authors emphasize that scaffolds have previously been created with a variety of solid free-form fabrication techniques, however, the fabrication and characterization of PCL scaffolds with varying internal architectures and porosities made through SLS has not been reported (10)

2 Low et al. (2001) investigated the construction of drug delivery devices by the technique of selective laser sintering (SLS). The authors emphasize that an important criterion required in the devices architecture are interconnected pores which can enable drugs to be embedded before the implantation and diffused into the biological environment. Using the technique of RP, macrostructure and porosity of the devices can be controlled varying the parameters of process (11). In drug delivery devices, controlling the porosity of the matrix is an important factor to control the drug release (12). Salmoria et al. (2007) studied the construction of porous parts, built by SLS, with different particle sizes of the high density polyethylene. This study showed that the pore size is a function of the particle size and the sintering degree (13). Polycaprolactone (PCL) is a polar bioresorbable polymer presenting low glass transition and melting temperature (-60 and 60 o C). The PCL amorphous phase presents high molecular mobility at body temperature what can aid its degradation by hydrolysis. The hydrolyzed products are reabsorbed by the body with minimal reaction of tissue (14). In this work, polycaprolactone specimens were built by selective laser sintering using particles size of µm under different laser energy densities. The effects of the energy density on the microstructure and mechanical properties were analyzed. EXPERIMENTAL The Polycaprolactone used was provided by the Sigma-Aldrich company. The material is in the form of pellets, molecular weight 80,000 g/mole, melting temperature of 60 0 C and density g/cm 3 at 25 C. The PCL was grinded cryogenically in a mechanical grinder and sieved. The particle size used in this work were µm. For the manufacture of specimens, the laser scanning speed was maintained at 39.8 mm/s and the energy density of the laser were 0.09; 0.14; 0.18; 0.23 and 0.27 (J/mm 2 ). The powder bad temperature was 45 o C. The specimens were tested in a single cantilever clamp, force controlled mode with rate of 2 N/min, using a DMA Q800. The stress versus strain curves were obtained at 30 o C. The particles form and size, the morphology of the surface specimens and the cryogenic fracture surface were examined with a scanning 11401

3 electron microscope (SEM), Philips XL30. All samples were coated with gold in a Bal-Tec Sputter Coater SCD005. RESULTS AND DISCUSSION The figure 1 shows the powder morphology of polycaprolactone after grinded. Can be observed that the material has a wide range size and shape. Figure 1 The Polycaprolactone powder after grinded. The figure 2 shows the micrographs of the surface of polycaprolactone with size of particle in the range of 150 to 212 µm, with different energy densities values of the laser beam: (a) 0.09 (b) 0.14 (c) 0.18 (d) 0.23 (e) 0.27 (J/mm 2 ). The SEM analyses showed that the PCL particles sintered with low energy density value (fig. 2(a)) present powder slightly fused together (small points of contact) and the particles can be identified. Can be observed that samples sintered with higher energy density value of laser beam results in a better fusion of the powder (Fig. 2(e)) presented highest degree of sintering and pore size minor when compared with samples sintered with minor energy density value. The figures 2 (b) to 2(e) showed coalescence of particles and interconnected pores distributed in the structure

4 (a) (d) (b) (e) (c) Figure 2 The samples surface sintered PCL ( µm): (a) 0,09; (b) 0,14; (c) 0,18; (d) 0,23; (e) 0,27 (J/mm 2 ). The micrographs of the cryogenic fractures surfaces (Figure 3) show that with increasing of the energy density there more coalescence of the particles, resulting in an increase in the width of necks

5 (a) (d) (b) (e) (c) Figure 3 - Cryogenic fractures surfaces sinterization of PCL( µm) with energy density of: (a) 0,09; (b) 0,14; (c) 0,18; (d) 0,23; (e) 0,27 (J/mm 2 ). The figure 4 shows the stress versus strain curves for samples manufactured with different energy densities. Since that the equipment had a limited force the failure was not verified on all specimens, the stress values were standardized and 11404

6 obtained at 16% of strain. For sample sintering with 0.09 to 0.23 J/mm 2 of energy density values presented a increased of the flexural modulus and stress at 16%, because the degree of sintering (increases the fluidity of the material) and the number of necks by area with greater thickness (table 1). However, the specimens manufactured with energy density of 0.27 J/mm 2 had a decreased in the value, which can be due to degradation of the material and / or due to uncertainty of the manufacturing process (instability of the laser or defects inherent the porous materials). In figure 4 can be observed that the deformation of the material decreases with increasing energy density due to increasing of the sintering degree of particles which makes the material more rigid J/mm J/mm J/mm J/mm J/mm 2 Stress (MPa) Strain (%) Figure 4 The stress versus strain curves of PCL sample ( µm) prepared with different energy density values

7 Table 1 Average mechanical properties of PCL sample prepared with different density energy values. Energy Density (J/mm 2 ) Flexure modulus (MPa) Stress at 16% CONCLUSION This work demonstrated the feasible of the manufacture of polycaprolactone specimens by SLS, with different pores size, for applications in drug delivery devices. The control of the porosity was conducted varying the energy density values of laser beam. Can be observed that specimens sintered with higher energy density values of laser beam results in a higher degree of sintering and pores size lower. The specimen presents coalescence of particles and interconnected pores distributed in the structure. The sample sintering with lower energy density values presented an decreased of the flexural modulus and stress at 16% and increased of deformation, because the degree of sintering. ACKNOWLEDGEMENTS The authors would like to thank FAPESC, CAPES, CNPq and FINEP for the financial support. REFERENCES (1) Jacobs, P.F. Rapid Prototyping and Manufacturing: Fundamentals of Sterelithography. : Society of Manufacturing Engineers,

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