Development of functionally-graded reservoir of PCL/PG by selective laser sintering for drug delivery devices

Abstract

Drug delivery devices are systems employed to conduct a drug to a specific site of the body, where it should be released and absorbed. Reservoir-type systems are devices in which the drug is contained within a nucleus isolated from the outside environment by a thin polymeric layer, which regulates a diffusion process driven by a functional concentration gradient. In this study two reservoir-type drug delivery devices based on polycaprolactone (PCL) were developed for the release of progesterone (PG) using the Selective Laser Sintering (SLS) technique, in order to investigate the influence of the concentration gradient promoted during manufacturing on the drug delivery profile. Two types of controlled-drug-release devices were fabricated; the first containing only the polycaprolactone polymer in the reservoir wall (system R) and the second containing PLC and 15% of progesterone in the wall (system R*). The cores of both reservoirs were filled with 40 mg of progesterone. A study on the degradation was conducted to assess the release process of the two systems. The drug delivery results showed that for both reservoirs the amount of drug released was linear over time, featuring zero-order release kinetics. The higher mass loss with the incorporation of the drug into the wall of the reservoir was associated with faster release of the drug to the medium. The feasibility of building threedimensional parts using the SLS technique allowed the construction of reservoir-type devices based on a functional gradient for the controlled-release of the drug.

Additive Manufacturing of PE/Fluorouracil Waffles for Implantable Drug Delivery in Bone Cancer Treatment

“…The microstructures of samples prepared via SLS depend on the process parameters (laser power, scan speed and spot diameter of the laser beam, and bed temperature) and the properties of the powder. For example, the particle shape and size distribution influence the powder packing density, while the melting flow behavior and the thermal stability determine the laser power and scan speed [4][5][6][7][8][9][10]. In recent years, SLS has demonstrated its potential in the biomedical field, for applications in bone tissue engineering, and for manufacturing drug delivery devices (DDDs) [5][6][7][8][9][10].…”

3D printing of PCL/Fluorouracil tablets by selective laser sintering: Properties of implantable drug delivery for cartilage cancer treatment

“…The particle size and shape along with the laser power are used to design and control the porosity of the polycaprolactone matrix and, consequently, control the drug release from DDDs [15][16][17][18][19].…”

“…The level of control over the microstructure of the SLS parts is dependent on the process parameters (laser power, scan speed and spot diameter of the laser beam, and bed temperature) and the powder properties. The particle shape and size distribution influence the powder packing density, while the melting flow behavior and the thermal stability define the laser power and scan speed [13][14][15][16][17][18][19]. In recent years, the SLS process has shown great prominence in the medical field, such as in the manufacturing of drug delivery devices (DDDs) [14][15][16][17][18][19].…”

The Age of Pharmaceutical 3d Printing. Technological and Therapeutical Implications of Additive Manufacturing.

“…Microporous controlled release drug delivery device [6] Oral dosage forms [24] Accelerated release formulations(ODT) [25] Reservoir-type drug delivery device [94] Candurin ® Gold Sheen [25,24] Eudragit ® E100 [57] Eudragit L100-55 [24] Eudragit ® RLPO [57] Hydroxypropyl methyl cellulose (HPMC) [25] Kollicoat IR [24] Kollidon VA 64 [25] Nylon [6,77] Poly(lactic acid) (PLA) [73] Polycaprolactone (PCL) [77] Poly(L-lactide) (PLLA) [77] Polyamide [77,6] Polypropylene [77] Polystyrene [77] Methylene blue [6] Paracetamol [25,24] Progesterone [77] required not applicable required * not necessarily present in the final dosage form; ** sometimes using casted films as printing support. [62,115,46,111,50,43,73] Materials and Methods FDM and PAM extrusion printing methods make use of solid filaments, semi-solids or viscous liquids that may be heated to different degrees, pushed through one, up to three nozzles and deposited on a solid and sometimes heated platform, layer upon layer, a process that shows similarities to traditional pharmaceutical wet and hot-melt extrusion techniques [20,46,62,66,73,115].…”