Eduardo Galdón

A biodegradable copolyester, poly(butylene succinate-co-ε-caprolactone) (PBS_CL), was used for first time as an excipient for pharmaceutical dosage forms using direct compression and hot processing techniques (ultrasound-assisted compression (USAC) and hot melt extrusion (HME)). Robust binary systems were achieved with hot processing techniques, allowing a controlled release of the drug. With only 12% v/v of PBS_CL, controlled release forms were obtained using USAC whereas in HME over 34% v/v of excipient is necessary. Amounts over 23% v/v allowed a long-extended release for more than 72 h following diffusional kinetic. Thanks to the high melting point of theophylline and the physicochemical properties of PBS_CL selected and synthesized, the structure of the excipient inside the USAC tablets and HME filaments corresponds to a continuum medium. A percolation threshold around 23% v/v was estimated, which agrees with a continuum percolation model. The polymer shows a high excipient efficiency value using HME and USAC. A nanostructured matrix with wall thicknesses lower than 0.1 µm was obtained. This leads to a very effective coating of the drug particles by the excipient, providing a slow and reproducible release. The present study therefore supports the use of PBS_CL, for the preparation of controlled release dosage forms using hot processing techniques.

Ultrasound assisted compression (USAC) is a manufacturing technique which applies thermal and mechanical energy to the powder bed, producing tablets with improved characteristics compared to the direct compression process. This technology is ideal for thermoplastic materials, as polyurethanes, whose particles usually undergo a sintering process. Thermoplastic polyurethanes are widely used in sustained drug release systems but rarely seen in tablets due to their elastic properties. The aim of this work is to investigate the ability of USAC to manufacture sustained release matrix tablets based on elastic thermoplastic polyurethanes (TPU), overcoming the limitations of direct compression. The technological and biopharmaceutical characteristics of the TPU matrices have been evaluated, with special focus on the porous structure due to the implications on drug release. For the first time, USAC has been successfully employed for manufacturing elastic thermoplastic polyurethanes-based matrices. TPU tablets show an inert character with a sustained drug release governed by a diffusional mechanism. Initial porosity of matrices was similar in all batches studied, with no influence of drug particle size, and a fractal nature of the pore network has been observed. SEM microphotographs show the continuum medium created by the sintering of the polymer, responsible for the high excipient efficiency.