Microparticle formation and its mechanism in single and double emulsion solvent evaporation.
The emulsification is the first step of the emulsification solvent evaporation method and has been extensively investigated. On the contrary the second step, the solvent transport out from the emulsion droplets that determine the particle morphology and with great influence on the microparticles encapsulation and release behavior has been scarcely studied. This study investigates the mechanism of the solvent elimination from the emulsion droplets and its influence on the particle morphology, encapsulation and release behavior. Usually, the solvent is highly volatile that makes the solvent elimination process very fast thus difficult to observe. In order to observe in detail the microparticle formation, the initial emulsion was monitored by optical microscope under controlled solvent evaporation conditions. The results from the optical microscopic observations corroborated with laser diffractometry analysis showed that in single emulsion formulations, spherical microparticles are formed by accelerated solvent elimination due to the combined effects of high solvent volatility and polymer precipitation. The solvent expulsion accompanied by important shrinkage generates on the microparticle surface a thin layer of nanoparticles attested by scanning electron microscopy and laser diffractometry. During the intense solvent elimination, the encapsulated substance is drained, affecting the loading efficiency. Furthermore, it will concentrate towards the microparticle surface contributing to the initial burst release. In double emulsion formulations, microparticles with different morphologies are generated due to the presence of the aqueous-phase microdroplets inside the emulsion droplet. During the solvent elimination, these microdroplets generally coalesce under the pressure of the precipitating polymer. Depending mainly on the polymer concentration and emulsification energies, the final microparticles will be a mixture of honeycomb, capsule or plain structure. During the shrinkage due to the incompressibility of the inner microdroplets, the precipitating polymer wall around them may break forming holes through which the encapsulated substance is partly expulsed. Through these holes, the encapsulated substance is further partitioning with the external aqueous phase during solvent evaporation and contributes to the initial burst release during the application.
Rosca
Iosif Daniel
ID
Department of Polymer Science, Faculty of Industrial Chemistry, Polytechnic University of Bucharest, Calea Victoriei, 149, Sector 1, Bucharest, Romania. rosca_iosif@yahoo.com
Watari
Fumio
F
Uo
Motohiro
M
D002214:Capsules; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004337:Drug Carriers / Q000737:chemistry / Q000493:pharmacokinetics; D016503:Drug Delivery Systems / Q000379:methods; D004655:Emulsions / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D006016:Glycolates / Q000737:chemistry / Q000493:pharmacokinetics; D019344:Lactic Acid; D007834:Lasers; D008752:Methylene Chloride / Q000737:chemistry / Q000493:pharmacokinetics; D008853:Microscopy / Q000295:instrumentation; D008863:Microspheres; D049329:Nanostructures / Q000737:chemistry / Q000648:ultrastructure; D010316:Particle Size; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; D016062:Porosity; D012997:Solvents / Q000737:chemistry / Q000493:pharmacokinetics*; D014835:Volatilization
D002214:Capsules; D004337:Drug Carriers; D004655:Emulsions; D006016:Glycolates; D011108:Polymers; D012997:Solvents; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D008752:Methylene Chloride