Browse > Article

Control of Encapsulation Efficiency and Initial Burst in Polymeric Microparticle Systems  

Yeo, Yeon (Purdue University, Departments of Pharmaceutics and Biomedical Engineering)
Park, Ki-Nam (Purdue University, Departments of Pharmaceutics and Biomedical Engineering)
Publication Information
Archives of Pharmacal Research / v.27, no.1, 2004 , pp. 1-12 More about this Journal
Abstract
Initial burst is one of the major challenges in protein-encapsulated microparticle systems. Since protein release during the initial stage depends mostly on the diffusional escape of the protein, major approaches to prevent the initial burst have focused on efficient encapsulation of the protein within the microparticles. For this reason, control of encapsulation efficiency and the extent of initial burst are based on common formulation parameters. The present article provides a literature review of the formulation parameters that are known to influence the two properties in the emulsion-solvent evaporation/extraction method. Physical and chemical properties of encapsulating polymers, solvent systems, polymer-drug interactions, and properties of the continuous phase are some of the influential variables. Most parameters affect encapsulation efficiency and initial burst by modifying solidification rate of the dispersed phase. In order to prevent many unfavorable events such as pore formation, drug loss, and drug migration that occur while the dispersed phase is in the semi-solid state, it is important to understand and optimize these variables.
Keywords
PLGA; Microparticle; Encapsulation efficiency; Release profile; Initial burst; Formulation parameters;
Citations & Related Records

Times Cited By Web Of Science : 73  (Related Records In Web of Science)
Times Cited By SCOPUS : 68
연도 인용수 순위
1 Boury, F., Marchais, H., Proust, J. E., and Benoit, J. P., Bovine serum albumin release from poly(alpha-hydroxy acid) microspheres: effects of polymer molecular weight and surface properties. J. Controlled Release, 45, 75-86 (1997)   DOI   ScienceOn
2 Cohen, S., Yoshioka, T., Lucarelli, M., Hwang, L. H., and Langer, R., Controlled delivery systems for proteins based on PLGA microspheres. Pharm. Res., 8, 713-720(1991)   DOI   ScienceOn
3 Crotts, G. and Park, T. G., Stability and release of bovine serum albumin encapsulated within PLGA microparticles. J. Controlled Release, 44, 123-134 (1997)   DOI   ScienceOn
4 Hora, M. S., Rana, R. K., Nunberg, J. H., Tice, T. R., Gilley, R. M., and Hudson, M. E., Release of human serum albumin from PLGA microspheres. Pharm. Res., 7, 1190-1194 (1990)   DOI   ScienceOn
5 Jeyanthi, R., Mehta, R. C., Thanoo, B. C., and Deluca, P P., Effect of processing parameters on the properties of peptide-containing PLGA microspheres. J. Microencapsulation, 14, 163-174(1997)   DOI   ScienceOn
6 Jeyanthi, R., Thanoo, B. C., Metha, R. C., and DeLuca, P. P., Effect of solvent removal technique on the matrix characteristics of polylactide/glycolide microspheres for peptide delivery. J. Controlled Release, 38, 235-244 (1996)   DOI   ScienceOn
7 Johansen, P., Men, Y., Audran, R., Corradin, G., Merkle, H. P., and Gander, B., Improving stability and release kinetics of microencapsulated tetanus toxoid by co-encapsulation of additives. Pharm. Res., 15, 1103-1110 (1998)   DOI   ScienceOn
8 Li, X., Deng, X., and Huang, Z., In Vitro Protein Release and Degradation of Poly-D,L-Iactide-poly(ethylene glycol) Microspheres with Entrapped Human Serum Albumin. Pharm. Res., 18, 117-124 (2001)   DOI   ScienceOn
9 Li, X., Deng, X., Yuan, M., Xiong, C., Huang, Z., Zhang, Y., and Jia, W., Investigation on process parameters involved in preparation of polylactide-poly(ethylene glycol) microspheres containing Leptospira Interrogans antigens. Int. J. Pharm., 178, 245-255 (1999)   DOI   ScienceOn
10 Mehta, R. C., Jeyanthi, R., Calis, S., Thanoo, B. C., Burton, K. W., and DeLuca, P. P., Biodegradable microspheres as depot system for parenteral delivery of peptide drugs. J. Controlled Release, 29, 375-384 (1994)   DOI   ScienceOn
11 Zhu, G. and Schwendeman, S. P., Stabilization of proteins encapsulated in cylindrical PLGA implants: mechanism of stabilization by basic additives. Pharm. Res., 17, 351-357 (2000)   DOI   ScienceOn
12 Tracy, M. A., Development and scale-up of a microsphere protein delivery system. Biotechnol. Prog., 14, 108-115 (1998)   DOI   PUBMED   ScienceOn
13 Uchida, T., Nagareya, N., Sakakibara, S., Konishi, Y., Nakai, A., Nishikata, M., Matsuyama, K., and Fukada, K., Preparation and characterization of polylactic acid microspheres containing bovine insulin by a w/o/w emulsion solvent evaporation method. Chem. Pharm. Bull., 45,1539-1543 (1997)   DOI   PUBMED   ScienceOn
14 van de Weert, M., van't Hof, R., van der Weerd, J., Heeren, R. M. A., Posthuma, G., Hennink, W. E., and Crommelin, D. J. A., Lysozyme distribution and conformation in a biodegradable polymer matrix as determined by FT-IR techniques. J. Controlled Release, 68, 31-40 (2000b)   DOI   ScienceOn
15 Sah, H., Toddywala, R., and Chien, Y. W., The influence of biodegradable microcapsule formulations on the controlled release of a protein. J. Controlled Release, 30, 201-211 (1994)   DOI   ScienceOn
16 Nihant, N., Schugens, C., Grandfils, C., Jerome, R., and Teyssie, P., Polylactide microparticles prepared by double emulsion/evaporation technique. I. Effect of primary emulsion stability. Pharm. Res., 11, 1479-1484 (1994)   DOI   ScienceOn
17 Park, T. G., Lee, H. Y., and Nam, Y. S., A new preparation method for protein loaded poly(D,L-lactic-co-glycolic acid) microspheres and protein release mechanism study. J. Controlled Release, 55, 181-191 (1998)   DOI   ScienceOn
18 Sinisterra, R. D., Shastri, V. P., Najjar, R., and Langer, R., Encapsulation and release of rhodium(lI) citrate and its association complex with hydroxypropyl-$\beta$-cyclodextrin from biodegradable polymer microspheres. J. Pharm. Sci., 88, 574-576 (1999)   DOI   ScienceOn
19 Huang, X. and Brazel, C. S., On the importance and mechanisms of burst release in matrix-controlled drug delivery systems. J. Controlled Release, 73, 121-136 (2001)   DOI   ScienceOn
20 Sah, H., Microencapsulation techniques using ethyl acetate as a dispersed solvent: effects of its extraction rate on the characteristics of PLGA microspheres. J. Controlled Release, 47, 233-245 (1997)   DOI   ScienceOn
21 van de Weert, M., Hennink, W. E., and Jiskoot, W., Protein instability in PLGA microparticles. Pharm. Res., 17, 1159-1167 (2000a)   DOI   ScienceOn
22 Lu, W. and Park, T. G., Protein release from poly(lactic-co-glycolic acid) microspheres: protein stability problems. PDA J. Pharm. Sci. Technol., 49, 13-19 (1995)
23 Walter, E., Dreher, D., Kok, M., Thiele, L., Kiama, S. G., Gehr, P., and Merkle, H. P., Hydrophilic poly(D,L-lactide-co-glycolide) microspheres for the delivery of DNA to human-derived macrophages and dendritic cells. J. Controlled Release, 76, 149-168 (2001)   DOI   ScienceOn
24 Yan, C., Resau, J. H., Hewetson, J., Mest, M., Rill, W L., and Kende, M., Characterization and morphological analysis of protein-loaded poly(lactide-co-glycolide) microparticles prepared by water-in-oil-in-water emulsion technique. J. Controlled Release, 32, 231-241 (1994)   DOI   ScienceOn
25 Yeo, Y., Basaran, O. A., and Park, K., A new process for making reservoir-type microcapsules using ink-jet technology and interfacial phase separation. J. Controlled Release, 93, 161-173 (2003)   DOI   ScienceOn
26 Frauke Pistel, K., Breitenbach, A., Zange-Volland, R., and Kissel, T., Brush-like branched biodegradable polyesters. Part III. Protein release from microspheres of poly(vinyl alcohol)-graft-poly(D,L-lactic-co-glycolic acid). J. Controlled Release, 73, 7-20 (2001)   DOI   ScienceOn
27 Jiang, G., Thanoo, B. C., and DeLuca, P. P., Effect of osmotic pressure in the solvent extraction phase on BSA release profile from PLGA microspheres. Pharm. Dev. Technol., 7, 391-399 (2002)   DOI   ScienceOn
28 Kim, H. K. and Park, T. G., Microencapsulation of human growth hormone within biodegradable polyester microspheres: protein aggregation stability and incomplete release mechanism. Biotechnol. Bioeng., 65, 659-667 (1999)   DOI   ScienceOn
29 Kissel, T., Y., X. L., Volland, C., Gorich, S., and Koneberg, R., Parenteral protein delivery systems using biodegradable polyesters of ABA block structure, containing hydrophobic poly(lactide-co-glycolide) A blocks and hydrophilic poly(ethylene oxide) B blocks. J. Controlled Release, 39, 315-326 (1996)   DOI   ScienceOn
30 Schugens, C., Laruelle, N., Nihant, N., Grandfils, C., Jerome, R., and Teyssie, P., Effect of the emulsion stability on the morphology and porosity of semicrystalline poly L-Iactide microparticles prepared by w/o/w double emulsion-evaporation. J. Controlled Release, 32, 161-176 (1994)   DOI   ScienceOn
31 Nihant, N., Schugens, C., Grandfils, C., Jerome, R., and Teyssie, P., Polylactide microparticles prepared by double emulsion-evaporation. II. Effect of the poly (Iactide-co-glycolide) composition on the stability of the primary and secondary emulsions. J. Colloid Interface Sci., 173, 55-65 (1995)   DOI   ScienceOn
32 Li, W.-I., Anderson, K. W., Mehta, R. C., and Deluca, P. P., Prediction of solvent removal profile and effect on properties for peptide-loaded PLGA microspheres prepared by solvent extraction/evaporation method. J. Controlled Release, 37, 199-214 (1995)   DOI   ScienceOn
33 Ogawa, Y., Yamamoto, M., Okada, H., Yashiki, T., and Shimamoto, T., A new technique to efficiently entrap leuprolide acetate into microcapsules of polylactic acid or copoly(lactic/glycolic) acid. Chem. Pharm. Bull., 36, 1095-1103 (1988)   DOI   PUBMED   ScienceOn
34 Bodmeier, R. and McGinity, J. W., Solvent selection in the preparation of PLA microspheres prepared by the solvent evaporation method. Int. J. Pharm., 43, 179-186 (1988)   DOI   ScienceOn
35 Maa, Y.- F. and Hsu, C. C., Effect of primary emulsions on microsphere size and protein-loading in the double emulsion process. J. Microencapsulation, 14, 225-241 (1997)   DOI   ScienceOn
36 Mehta, R. C., Thanoo, B. C., and DeLuca, P. P., Peptide containing microspheres from low molecular weight and hydrophilic poly(D,L-lactide-co-glycolide). J. Controlled Release, 41, 249-257 (1996)   DOI   ScienceOn
37 Rafati, H., Coombes, A. G. A., Adler, J., Holland, J., and Davis, S. S., Protein-loaded PLGA microparticles for oral administration: formulation, structural and release characteristics. J. Controlled Release, 43, 89-102 (1997)   DOI   ScienceOn
38 Wang, H. T., Schmitt, E., Flanagan, D. R., and Linhardt, R. J., Influence of formulation methods on the in vitro controlled release of protein from poly(ester) microspheres. J. Controlled Release, 17, 23-32 (1991)   DOI   ScienceOn
39 Yang, Y.-Y., Chia, H.-H., and Chung, T.-S., Effect of preparation temperature on the characteristics and release profiles of PLGA microspheres containing protein fabricated by double-emulsion solvent extraction/evaporation method. J. Controlled Release, 69, 81-96 (2000)   DOI   ScienceOn
40 Igartua, M., Hernandez, R. M., Esquisabel, A., Gascon, A. R., Calvo, M. B., and Pedraz, J. L., Influence of formulation variables on the in vitro release of albumin from biodegradable microparticulate systems. J. Microencapsulation, 14, 349-356 (1997)   DOI   ScienceOn
41 Schwendeman, S. P., Recent advances in the stabilization of proteins encapsulated in injectable PLGA delivery systems. Crit Rev Ther Drug Carrier Syst, 19, 73-98 (2002)   DOI   PUBMED   ScienceOn
42 Alkermes, Medisorb Polymer Products (http://www.alkermes.com/polymer/produchts.html)
43 Hsu, Y.-Y., Hao, T., and Hedley, M. L., Comparison of process parameters for microencapsulation of plasmid DNA in poly(D,L-lactic-co-glycolic) acid microspheres. J. Drug Targeting, 7, 313-323(1999)   DOI   ScienceOn
44 Lee, W.-k., Park, J.-y., Yang, E. H., Suh, H., Kim, S. H., Chung, D. S., Choi, K., Yang, C. W., and Park, J.-S., Investigation of the factors influencing the release rates of cyclosporin A-loaded micro- and nanoparticles prepared by high-pressure homogenizer. J. Controlled Release, 84, 115-123 (2002)   DOI   ScienceOn
45 O'Hagan, D. T., Jeffery, H., and Davis, S. S., The preparation and characterization of PLGA microspheres: III. Microparticle/polymer degradation rates and the in vitro release of a model protein. lnt. J. Pharm., 103, 37-45 (1994)   DOI   ScienceOn
46 Sah, H. K., Toddywala, R., and Chien, Y. W., Biodegradable microcapsules prepared by a w/o/w technique: effects of shear force to make a primary w/o emulsion on their morphology and protein release. J. Microencapsulation, 12, 59-69 (1995)   DOI   ScienceOn
47 Schlicher, E. J. A. M., Postma, N. S., Zuidema, J., Talsma, H., and Hennink, W. E., Preparation and characterization of poly(D,L-lactic-co-glycolic acid) microspheres containing desferrioxamine.lnt. J. Pharm., 153, 235-245 (1997)   DOI   ScienceOn
48 Yamaguchi, Y., Takenaga, M., Kitagawa, A., Ogawa, Y., Mizushima, Y., and Igarashi, R., Insulin-loaded biodegradable PLGA microcapsules: initial burst release controlled by hydrophilic additives. J. Controlled Release, 81, 235-249 (2002)   DOI   ScienceOn
49 Yang, Y.-Y., Chung, T.-S., and Ping Ng, N., Morphology, drug distribution, and in vitro release profiles of biodegradable polymeric microspheres containing protein fabricated by double-emulsion solvent extraction/evaporation method. Biomaterials, 22, 231-241 (2001)   DOI   ScienceOn