Technique to encapsulate a low molecular weight hydrophilic drug in biodegradable polymer particles in a liquid–liquid system

In the present study, we present a novel technique for producing particles comprising isoniazid (INZ), a low molecular weight hydrophilic drug, encapsulated by poly (lactide-co-glycolide) (PLGA), a biodegradable polymer, in a liquid–liquid system. The preparation of polymer particles encapsulating a low molecular weight hydrophilic drug in a liquid–liquid system usually yields empty particles (the drug loading efficiency = 0%). PLGA particles encapsulating approximately 6.0% INZ as a hydrophilic model drug of molecular weight (Mw) 137 were prepared by solvent evaporation from a w1/(o1 + o2)/w2 emulsion. The drug loading efficiency of the PLGA particles was increased slightly to approximately 8.0% by replacing the w1/(o1 + o2)/w2 emulsion with a w/(o1 + o2)/o3 emulsion. We propose a novel technique for preparing PLGA particles with an improved drug loading efficiency by freezing the inner water phase of the primary w/(o1 + o2) emulsion at −10 °C, followed by the evaporation of the solvent from the secondary w/(o1 + o2)/o3 emulsion. The drug loading efficiency of the resulting PLGA particles was higher than that of the PLGA particles produced from a w/(o1 + o2)/o3 emulsion at room temperature compared to 8.0%. The novel technique we propose in the current paper may be used to encapsulate various hydrophilic substances besides a hydrophilic drug in polymer particles in a liquid–liquid system.