Processes for Microencapsulation

Laine, P., Toppinen, E., Kivela, R., Taavitsainen, V-M., Knuutila, O., Sontag-Strohm, T.,Jouppila, K. Loponen, J.(2011), Emulsion preparation with modified oat bran Optimization of the emulsification process for microencapsulation purposes. 

Rocha-Selmi, G.A., Theodora, A.C., Thomazini, M., Bolini, H.M.A., and Favaro-Trindade, C.S. Double emulsion stage prior to complex coacervation process for microencapsulation of sweetener sucralose. Journal of Food Engineering 119(1) (2013) 28-32. 

Wang R, Tian Z, Chen L (2011) A novel process for microencapsulation of fish oil with harley protein. Food Research International 44 2735-2741. 

Kalishek, R. J. Hayford, D. E. Process for microencapsulation without capsule agglomeration. US 5164126,1992. 

Re MI. Microencapsulation by spray drying. Drying Technol 1998 16(6) 1195-1236. Wan LS, Heng PW, Chia CG. Spray drying as a process for microencapsulation and the effect of different coating polymers. Drug Dev Ind Pharm 1992 18(9) 997-1011. Sutinen R, Laasanen V, Paronen P, Urtti A. pH-controlled silicone microspheres for controlled drug delivery. J Controlled Release 1995 33 163-171. 

Phase separation microencapsulation procedures are suitable for entrapping water-soluble agents in lactide/glycolide excipients. Generally, the phase separation process involves coacervation of the polymer from an organic solvent by addition of a nonsolvent such as silicone oil. This process has proven useful for microencapsulation of water-soluble peptides and macromolecules (48). 

RESS [Rapid Expansion of Supercritical Solutions] A process for depositing a film of solid material on a surface. The substance is dissolved in supercritical carbon dioxide. When the pressure is suddenly reduced, the fluid reverts to the gaseous state and the solute is deposited on the walls of the vessel. Used for size-reduction, coating, and microencapsulation. First described in 1879. Developed in 1983 by R. D. Smith at the Battelle Pacific Northwest Laboratory. 

As the coacervate forms, it must wet the suspended core particles or core droplets and coalesce into a continuous coating for the process of microencapsulation to occur. The final step for microencapsulation is the hardening of the coacervate wall and the isolation of the microcapsules, usually the most difficult step in the total process. 

Reis, C. P, Neufeld, R. J., Vile la, S., Ribeiro, A. J., and Veiga, F. (2006), Review and current status of emulsion/dispersion technology using an internal gelation process for the design of alginate particles, /. Microencapsul., 23(3), 245-257. 

Ransone CM, Eyman IV, Litzinger D, CoUoton M, and Shah SS. 1999, A novel microencapsulation process for sustained dehvery of proteins. Proc. Inter. Symp. Control. Release Bioact. Mater. 1999 26 603-604. 

Nerlich, B. Gustafsson, J. Mank, R. Horig, J. Kochling, W. Process for the Microencapsulation of Water-Soluble MedicamentsDE Patent 42, 23 169 Cl, November 25, 1993. 

For polymorphic compounds, such as sulfa drugs, talc excipients induced polymorphic transformation of sulfamethoxazole during the process of microencapsulation by spray-drying,... 

Debenedetti and coworkers (88,89) provided one of the first examples of microencapsulation of a drug in the polymeric matrix. Richard and coworkers (90) provided a recent example of the microencapsulation process when they produced microparticles with the encapsulated model protein that showed sustained release. Foster and coworkers (87) also reported precipitation of copper-indomethacin by PVP with a 96-fold enhancement in the dissolution rate of indomethacin. These examples clearly demonstrated the advantages of using supercritical fluid processing for the preparation of polymer-drug formulations with potentially improved therapeutic properties. 

Large lots can be prepared on a commercial-scale plant (XlOO, Fig. 8), where several tens of kilograms of particles can be obtained daily, either by RESS, antisolvent, or microencapsulation processes. For a nonpharmaceutical application, we envisage modifying a large SFE plant (XIOOO, Fig. 9) for processing at least 1000 kg of powder per day by an antisolvent process. 

Although other water soluble polymers have also been used, viable mammalian cells have been encapsulated most frequently in stabilized calcium alginate. Sun pioneered this process to microencapsulate pancreatic islets (2). The thin calcium alginate/polylysine capsule wall was able to protect the transplanted islets from the immune system of the host rats (chemically induced diabetes) for 2-3 weeks initially and with further refinement for as much as two years (3,4). The feasibility of this approach has been shown in various animals (5-8). The long term success in rats has been questioned, however, because of the problem of pancreas regeneration in chemically induced diabetic animals (9). 

Human Burkitt Lymphoma ( Raji ) cells were obtained frozen from the American Type Culture Collection thawed, and cultured, in RPMI containing 10% Fetal Bovine Serum. The polymers for microencapsulation were dissolved in distilled water with pH adjustment to 7.4, and dialysed extensively against distilled water through a 104 Da cut off dialysis bag. The polymers were then pH adjusted to 7.4 and freeze dried to constant weight. Final preparation for the microencapsulation process was limited to dissolution in appropriate medium and filtration through a 0.4 pm cartridge. 

Hsu Y Y, Hao T, Hedley M L (1999). Comparison of process parameters for microencapsulation of plasmid DNA in poly(D,L-lactic-co-glycolic) acid microspheres. /. Drug Target. 7 313-323. 

Many processes for making microencapsulated product have been reported in the literature. They encompass a broad range of scientific and engineering disciplines. Some are used in high volume applications as in carbonless copy paper, others are in low volume specialty applications many are used in pilot plant scale. 

Polymerization plays a key role in chemical microencapsulation. The basic mechanism of this method is to put a polymer wall (can be multilayer) through polymerization on a core material, which is in a form of small liquid droplets, solid particles, or even gas bubbles or to embed the core material in a polymer matrix through polymerization. Interfacial polymerization is one of the most important methods that have been extensively developed and industrialized for microencapsulation. According to Thies and Salaun, interfacial polymerization includes live types of processes represented by the methods of emulsion polymerization, suspension polymerization, dispersion polymerization, interfacial polycondensation/polyaddition, and in situ polymerization. This chapter is only focnsed on interfacial polycondensation and polyaddition in a narrow sense of interfacial polymerization. 

Then, S. Neon, G. S. Kasim, N. H. A. Optimization of microencapsulation process for self-healing polymeric materials. Sains Malaysiana (2011), 40(7), 795-802. 

Mauguet, M.C., Legrand, J., Brujes, L., Camelle, G., Larre, C., Popineau, Y., 2002. Gliadin matrices for microencapsulation processes by simple coacervation method. J. Microencapsul. 19(3), 377-384. 

---