Arlette Vega-González

Composite fibrous biomaterials for tissue engineering obtained using a supercritical CO2 antisolvent process

Several techniques have been proposed for producing porous structures or scaffolds for tissue engineering but, as yet, with no optimal solution. With regard to this topic, this paper focuses on the preparation of biocompatible nanometric filler-polymer composites organized in a network of fibers. Titanium dioxide (TiO2) or hydroxyapatite (HAP) nanopowders as the guest particles and poly(lactic acid) (L-PLA) or the blend poly(methylmethacrylate)/poly(epsilon-caprolactone) (PMMA/PCL) as the polymer carrier were selected as model systems for this purpose. A supercritical antisolvent technique was used to produce the composites. In the process developed, the non-soluble particulate filler was suspended in a polymer solution, and both components were sprayed simultaneously into supercritical carbon dioxide (scCO2). Using this technique, polymeric matrices were loaded with approximately 10-20 wt.% of inorganic phase distributed throughout the composite. Two different hybrid materials were prepared: a PMMA/PCL+TiO2 system where either fibers or microparticles were prepared by varying the molecular weight of the used PMMA; and fibers in the case of L-PLA+HAP system. After further post-processing in a three-dimensional network, these nanofibers can potentially be used as scaffolds for tissue engineering.

Impregnation of an intraocular lens for ophthalmic drug delivery.

In this work the possibility of impregnating P(MMA-EHA-EGDMA) with flurbiprofen using a clean and environmentally friendly technology, namely supercritical fluid technology was evaluated. P(MMA-EHA-EGDMA) has been proposed as a promising matrix to be used for intraocular delivery of anti-inflammatory drugs used in eye surgery and flurbiprofen is a non-steroidal anti-inflammatory agent. Fundamental studies like, the solubility of the drug in carbon dioxide, as well as the sorption degree of this polymeric matrix in the presence of carbon dioxide have been previously carried out. The aim of this research was to evaluate the effects of these two variables in the impregnation process. Different experimental conditions were tested and the results obtained suggest that the best impregnating conditions for this system are low temperatures and pressures, which at the same time correspond to a lower solubility of the drug in the supercritical fluid and a low swelling of the polymeric matrix. Experiments performed also indicate that the batch impregnation process leads to higher yields of impregnation and according to the release profiles obtained the drug can be released from the matrix up to three months, which presents great advantages for post-surgical treatments.

CRYSTALLIZATION OF DRUGS USING SUPERCRITICAL CO2 AS ANTISOLVENT: FROM PHASE EQUILIBRIA TO PRODUCTS

The demand for green technologies is continually increasing due to the growing consciousness of alimentary, environmental and toxicity risks. Supercritical technologies have beneficed from that interest and have therefore received increased attention as propitious media for elaboration of materials in general and formation of particles in particular, especially for pharmaceutical applications. This work presents the recrystallization of several drugs from liquid organic solutions, using CO2 as the precipitating agent. Three drugs were specially studied: theophylline, tolbutamide and griseofulvin. To select the suitable process among the several potentialities offered by SCF and to further understand and interpret the crystallization behaviour, selected phase behaviour of binary and ternary systems involving solute-solvent-CO2 were investigated and are presented hereby as background. Drugs were further precipitated by compressed CO2 as antisolvent, and experimental data focused mostly on results obtained in the discontinuous stirred version of the process. There was special emphasis on the influence of stirring and CO2 introduction rates upon the crystals characteristics and the production yields. The main difference between the investigated drug-solvent systems was their sensitivity to the stirring. As a first step, macro- and micro-mixing times were estimated; it was shown that mixing times due to circulation and to molecular diffusion were in the same range, with no significant breakthrough as a function of the solvent. Since the large size of particles produced by batch might be detrimental for therapeutic applications and/or administration routes, several precipitations were performed in the semi-continuous mode. Conditions were varied in order to play with phase behaviour, i.e. by setting the pressure below or above the critical locus of the solvent-CO2 system. Morphology of particles suggested that precipitation was confined within the solvent droplets, originating smaller precipitates than particles produced at monophasic conditions. The results obtained for three systems show that size of precipitates can be manipulated by a proper selection of thermodynamics and time or space scales, although the later has to be more accurately investigated to view the two versions of the antisolvent processes as complementary.