Impact of Hydro-Alcoholic Solvents on the Oil and Phenolics Extraction from Walnut (Juglans regia L.) Press-Cake and the Self-Emulsification of Extracts.

The objective was to evaluate the performance of four hydro-alcoholic solvents to simultaneously extract oil and more polar molecules as phenolics, among others, to produce complex extracts that eventually could self-emulsify after solvent removal. Walnut press-cake was selected as the sourcing material. Extractions were performed as a semi-continuous operation up to a solvent-to-solid ratio of 28, with a fractional collection of the effluent. Among the solvents, labelled by their alcohol content EtOH 58, EtOH 86, iPro 60 and iPro 90 for ethanol (EtOH) and isopropanol (iPro), iPro 90 allowed to reach an oil extraction efficiency of 97% while the recovery for the other solvents was in the range of 30-40%. For both alcohols, the increase of the solvent hydration negatively influenced the oil extraction but positively increased the recovery of phenolics that reached 17.6 mg GAE/gcake when EtOH 58 was used. Several fractions contained enough surface-active material and oil to self-assemble as emulsions. IPro 90 and EtOH 86 showed better performances in the sense that most extracts were able to emulsify, though extraction kinetics pointed out differences. The most hydrated solvents behaved equally, with extraction yields in the same range and a similar but limited emulsifying capacity of only few fractions.

Improvement of the oxidative stability of camelina oil by enrichment with phospholipid-quercetin formulations.

Camelina oil (Coil) contains 50-60% of polyunsaturated fatty acids which are susceptible to oxidation. In this work, addition of phospholipids (0-20 mg/g) was assessed to improve the solubility of quercetin in Coil and enhance its oxidative stability. Results showed that the solubility of quercetin in Coil increased up to 7.7-fold by phospholipid addition. The solubility of quercetin in Coil was correlated to the phospholipid concentration and reached a maximum value of 1 298 µg/g. The addition of phospholipid-quercetin formulations increased the Coil stability, measured at 60 °C, from 24 h up to 115 h. Coil saturated with only quercetin (168 µg/g) did not significantly increase Coil stability, whereas phospholipids alone extended the oxidation lag time up to 40 h. This work successfully developed a solvent-free method for improving the solubility of quercetin in Coil and enhance its oxidative stability.

Characterization of azacytidine/poly(L-lactic) acid particles prepared by supercritical antisolvent precipitation.

A controlled azacytidine release system based on drug encapsulation with a polymer material has been prepared and characterized. The drug systems were prepared by precipitation from solutions, using supercritical CO2 antisolvent technique operating in a semi-continuous mode. Azacytidine was dissolved in dimethylsulfoxide and poly-lactic acid in methylene chloride. The two solutions were mixed before being sprayed into the supercritical reactor. Experimental conditions were 40 degrees C for temperature, 11 MPa for pressure, and a CO2 flow rate of 30 ml min(-1). The precipitated drug-polymer particles were further characterized to determine the percentage of encapsulated drug and establish the delivery kinetics under various release conditions. A sustained delivery of the drug over a period of various hours was obtained. Besides, an improved stability of the coated drug with respect to the pure azacytidine was found, thus proving the suitability of this approach for dealing with unstable compounds.

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.

Theophylline formulation by supercritical antisolvents.

Supercritical antisolvent precipitation has been used to produce theophylline particles as pure crystals or as a solid formulation with poly lactic acid (PLA). Experiments were carried out as batch or semi-continuous process and with carbon dioxide (CO2) or trifluoromethane (CHF3) as antisolvent. Both modes led to micronized theophylline, but the semi-continuous produced smaller particles than the batch. The particle morphology was sensitive to the antisolvent, since CO2- and CHF3-samples exhibited hexagonal and triangular shape, respectively. The most distinguish feature of CO2-powders was that theophylline exhibited a different crystal lattice than the crude- or the CHF3-materials, accredited by new diffraction peaks in the XRD patterns not attributable to hydration of samples. However, neither the shape nor the new crystal lattice influenced the dissolution kinetics of Theophylline. For co-precipitation with PLA, the successful recovery of a powder occurred only in conditions of CHF3-batch and CO2-semi continuous. The powder retained the shape and the crystallinity of the corresponding pure processed theophylline, indicating that PLA did not interfere with the precipitation behavior of the drug. Moreover, only the CO2-semi continuous products exhibited a decreased release rate and a prolongation of the total release time of the drug.

Preparation of acetazolamide composite microparticles by supercritical anti-solvent techniques.

The possibility of preparation of ophthalmic drug delivery systems using compressed anti-solvent technology was evaluated. Eudragit RS 100 and RL 100 were used as drug carriers, acetazolamide was the model drug processed. Compressed anti-solvent experiments were carried out as a semi-continuous or a batch operation from a liquid solution of polymer(s)+solute dissolved in acetone. Both techniques allowed the recovery of composite particles, but the semi-continuous operation yielded smaller and less aggregated populations than the batch operation. The release behaviour of acetazolamide from the prepared microparticles was studied and most products exhibited a slower release than the single drug. Moreover, the release could be controlled to some extent by varying the ratio of the two Eudragit used in the formulation and by selecting one or the other anti-solvent technique. Simple diffusion models satisfactorily described the release profiles. Composites specifically produced by semi-continuous technique have a drug release rate controlled by a diffusion mechanism, whereas for composites produced by the batch operation, the polymer swelling also contributes to the overall transport mechanism.