Nanostructured microspheres produced by supercritical fluid extraction of emulsions

Abstract

The system poly(lactic-co-glycolic) acid/ piroxicam (PLGA/PX) was selected, as a model system, to evaluate the effectiveness of supercritical carbon dioxide (SC-CO(2)) extraction of the oily phase (ethyl acetate) from oil-in-water emulsions used in the production of polymer/drug microspheres for sustained drug release applications. The influence of process parameters like operating pressure and temperature, flow rate and contacting time between the emulsion and SC-CO(2) was studied with respect to the microsphere size, distribution and solvent residue. Different polymer concentrations in the oily phase were also tested in emulsions formulation to monitor their effects on droplets and microspheres size distribution at fixed mixing conditions. Spherical PLGA microspheres loaded with PX (10% w/w) with mean sizes ranging between 1 and 3 microm and very narrow size distributions were obtained due to the short supercritical processing time (30 min) that prevents the aggregation phenomena typically occurring during conventional solvent evaporation process. A solvent residue smaller than 40 ppm was also obtained at optimized operating conditions. DSC and SEM-EDX analyses confirmed that the produced microparticles are formed by a solid solution of PLGA and PX and that the drug is entrapped in an amorphous state into the polymeric matrix with an encapsulation efficiency in the range of 90-95%. Drug release rate studies showed very uniform drug concentration profiles, without any burst effect, confirming a good dispersion of the drug into the polymer particles.

NSAID Drugs Release from Injectable Microspheres Produced by Supercritical Fluid Emulsion Extraction

“…The supercritical extraction technology requires the optimization of several operating parameters such as, operating pressure and temperature, SC‐CO 2 flow rate, and processing time to avoid coalescence or aggregation phenomena inside the processed emulsion. In a previous work, optimized operating conditions for PLGA were found to be 80 bar and 38°C, with a flow rate of 0.5 kg/h for 30 min, when 50 g of emulsion with an oily phase content less than 20% w/w were used 27. Therefore, in this work, all the emulsions were processed using these process conditions.…”

“…A different approach starting from an emulsion and using SC‐CO 2 for the extraction of the emulsion organic phase was proposed by Chattopadhyay et al,26 in the preparation of drug microparticles of megesterol acetate or cholesterol acetate and in the formation of lipid microspheres charged with ketoprofen and indometacin. Della Porta and Reverchon,27 recently, gave some indications on the mechanism of solvent extraction by SC‐CO 2 of an oil‐in‐water emulsion for the production of polymer microspheres controlling their size, distribution, and drug loading by varying both emulsion and SC‐CO 2 process conditions.…”

Supercritical fluids applications in nanomedicine

“…The emulsions were prepared with a different percentage of PLGA from 2.5 to 7.5% in the oily phase. The obtained microspheres using SC-CO 2 technology, showed a particles size distribution narrower than the ones obtained by conventional evaporation and their encapsulation efficiency ranged between 80 and 95%; whereas, a smaller encapsulation efficiency was measured for microspheres produced by solvent evaporation [58]. The same technology was used to produce PLGA microspheres charged with two non-steroidal anti-inflammatory drug (NSAIDs): Piroxicam and Diclophenac sodium [48].…”

“…Reported encapsulation efficiency is high both for drugs and inorganic nanoparticles. Della Porta and Reverchon [48,58], gave some indications about the mechanism of solvent extraction by SC-CO 2 from an O/W emulsion and a W/O/W, during the production of PLGA microspheres. When the emulsion and SC-CO 2 come in contact, the mass transfer of the organic solvent can proceed by two parallel pathways: (A) diffusion of the organic solvent into water followed by the subsequent extraction of the solvent from the aqueous phase by SC-CO 2 ; (B) direct extraction upon contact between SC-CO 2 and the organic phase inside the droplet.…”

“…Its encapsulation in PLGA can resolve the problem and can also allow a sustained release of the drug during time. Della Porta and Reverchon [58] suggested the use of an oil-in-water (O/W) emulsion prepared using ethyl acetate and water (ratio 20:80). The same authors also proposed a systematic comparison, starting from the same emulsion, between the characteristics of the microspheres obtained by SC-CO 2 extraction and by conventional solvent evaporation.…”