Preparation of protein loaded chitosan microparticles by combined precipitation and spherical agglomeration

Andrea Fodor-Kardos, J. Tóth, Janos Gyenis

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Combined precipitation and spherical agglomeration was carried out in the non-miscible region of ethyl acetate-ethanol-water ternary solvent system. At first, w/o type quasi emulsion was prepared by sequential introduction of aqueous solutions of human serum albumin (HSA), chitosan (CS), and poly(4-styrenesulfonate) (PSS) into an ethyl acetate-ethanol solvent mixture. HSA was used to model a protein type drug, while CS and PSS served as matrix material in the obtained composite particles. PSS also served as chemical precipitation agent for both of the HSA and CS. The solubility of all these substances was reduced by introduction of additional amounts of ethyl acetate-ethanol mixture and/or ethanol as poor solvents. Due to the counter-diffusion of the good and poor solvents between the water rich droplets and the ethyl acetate-ethanol rich continuous phase, the aqueous phase gradually disappeared and partial agglomeration of the precipitated solids and their transfer to the continuous organic phase took place. The paper gives a report on the effect of several process variables on the quality of the obtained microparticles, such as their shape and stability against disintegration. The effects of the composition of the ternary solvent mixture, the route of its variation, the feeding method and composition of the added poor solvents, the stirring rate and the duration of agitation were studied. Spherical agglomeration was carried out in EtOAc-EtOH-H2 O ternary system. The model drug was human serum albumin. The paper describes the effects of the most important process variables. Under given conditions nearly spherical shape agglomerates was achieved. The paper proposes a probable mechanism of formation of the composite microparticle.

Original languageEnglish
Pages (from-to)16-25
Number of pages10
JournalPowder Technology
Volume244
DOIs
Publication statusPublished - Aug 2013

Fingerprint

Chitosan
Agglomeration
Proteins
Ethanol
Serum Albumin
Water
Disintegration
Composite materials
Ternary systems
Emulsions
Chemical analysis
Pharmaceutical Preparations
Solubility
ethyl acetate

Keywords

  • Antisolvent precipitation
  • Chemical precipitation
  • Controlled drug release
  • HSA/chitosan composite particles
  • Spherical agglomeration

ASJC Scopus subject areas

  • Chemical Engineering(all)

Cite this

Preparation of protein loaded chitosan microparticles by combined precipitation and spherical agglomeration. / Fodor-Kardos, Andrea; Tóth, J.; Gyenis, Janos.

In: Powder Technology, Vol. 244, 08.2013, p. 16-25.

Research output: Contribution to journalArticle

@article{62fc00be649e43aa94b1c66d92eae7a2,
title = "Preparation of protein loaded chitosan microparticles by combined precipitation and spherical agglomeration",
abstract = "Combined precipitation and spherical agglomeration was carried out in the non-miscible region of ethyl acetate-ethanol-water ternary solvent system. At first, w/o type quasi emulsion was prepared by sequential introduction of aqueous solutions of human serum albumin (HSA), chitosan (CS), and poly(4-styrenesulfonate) (PSS) into an ethyl acetate-ethanol solvent mixture. HSA was used to model a protein type drug, while CS and PSS served as matrix material in the obtained composite particles. PSS also served as chemical precipitation agent for both of the HSA and CS. The solubility of all these substances was reduced by introduction of additional amounts of ethyl acetate-ethanol mixture and/or ethanol as poor solvents. Due to the counter-diffusion of the good and poor solvents between the water rich droplets and the ethyl acetate-ethanol rich continuous phase, the aqueous phase gradually disappeared and partial agglomeration of the precipitated solids and their transfer to the continuous organic phase took place. The paper gives a report on the effect of several process variables on the quality of the obtained microparticles, such as their shape and stability against disintegration. The effects of the composition of the ternary solvent mixture, the route of its variation, the feeding method and composition of the added poor solvents, the stirring rate and the duration of agitation were studied. Spherical agglomeration was carried out in EtOAc-EtOH-H2 O ternary system. The model drug was human serum albumin. The paper describes the effects of the most important process variables. Under given conditions nearly spherical shape agglomerates was achieved. The paper proposes a probable mechanism of formation of the composite microparticle.",
keywords = "Antisolvent precipitation, Chemical precipitation, Controlled drug release, HSA/chitosan composite particles, Spherical agglomeration",
author = "Andrea Fodor-Kardos and J. T{\'o}th and Janos Gyenis",
year = "2013",
month = "8",
doi = "10.1016/j.powtec.2013.03.052",
language = "English",
volume = "244",
pages = "16--25",
journal = "Powder Technology",
issn = "0032-5910",
publisher = "Elsevier",

}

TY - JOUR

T1 - Preparation of protein loaded chitosan microparticles by combined precipitation and spherical agglomeration

AU - Fodor-Kardos, Andrea

AU - Tóth, J.

AU - Gyenis, Janos

PY - 2013/8

Y1 - 2013/8

N2 - Combined precipitation and spherical agglomeration was carried out in the non-miscible region of ethyl acetate-ethanol-water ternary solvent system. At first, w/o type quasi emulsion was prepared by sequential introduction of aqueous solutions of human serum albumin (HSA), chitosan (CS), and poly(4-styrenesulfonate) (PSS) into an ethyl acetate-ethanol solvent mixture. HSA was used to model a protein type drug, while CS and PSS served as matrix material in the obtained composite particles. PSS also served as chemical precipitation agent for both of the HSA and CS. The solubility of all these substances was reduced by introduction of additional amounts of ethyl acetate-ethanol mixture and/or ethanol as poor solvents. Due to the counter-diffusion of the good and poor solvents between the water rich droplets and the ethyl acetate-ethanol rich continuous phase, the aqueous phase gradually disappeared and partial agglomeration of the precipitated solids and their transfer to the continuous organic phase took place. The paper gives a report on the effect of several process variables on the quality of the obtained microparticles, such as their shape and stability against disintegration. The effects of the composition of the ternary solvent mixture, the route of its variation, the feeding method and composition of the added poor solvents, the stirring rate and the duration of agitation were studied. Spherical agglomeration was carried out in EtOAc-EtOH-H2 O ternary system. The model drug was human serum albumin. The paper describes the effects of the most important process variables. Under given conditions nearly spherical shape agglomerates was achieved. The paper proposes a probable mechanism of formation of the composite microparticle.

AB - Combined precipitation and spherical agglomeration was carried out in the non-miscible region of ethyl acetate-ethanol-water ternary solvent system. At first, w/o type quasi emulsion was prepared by sequential introduction of aqueous solutions of human serum albumin (HSA), chitosan (CS), and poly(4-styrenesulfonate) (PSS) into an ethyl acetate-ethanol solvent mixture. HSA was used to model a protein type drug, while CS and PSS served as matrix material in the obtained composite particles. PSS also served as chemical precipitation agent for both of the HSA and CS. The solubility of all these substances was reduced by introduction of additional amounts of ethyl acetate-ethanol mixture and/or ethanol as poor solvents. Due to the counter-diffusion of the good and poor solvents between the water rich droplets and the ethyl acetate-ethanol rich continuous phase, the aqueous phase gradually disappeared and partial agglomeration of the precipitated solids and their transfer to the continuous organic phase took place. The paper gives a report on the effect of several process variables on the quality of the obtained microparticles, such as their shape and stability against disintegration. The effects of the composition of the ternary solvent mixture, the route of its variation, the feeding method and composition of the added poor solvents, the stirring rate and the duration of agitation were studied. Spherical agglomeration was carried out in EtOAc-EtOH-H2 O ternary system. The model drug was human serum albumin. The paper describes the effects of the most important process variables. Under given conditions nearly spherical shape agglomerates was achieved. The paper proposes a probable mechanism of formation of the composite microparticle.

KW - Antisolvent precipitation

KW - Chemical precipitation

KW - Controlled drug release

KW - HSA/chitosan composite particles

KW - Spherical agglomeration

UR - http://www.scopus.com/inward/record.url?scp=84877142490&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84877142490&partnerID=8YFLogxK

U2 - 10.1016/j.powtec.2013.03.052

DO - 10.1016/j.powtec.2013.03.052

M3 - Article

VL - 244

SP - 16

EP - 25

JO - Powder Technology

JF - Powder Technology

SN - 0032-5910

ER -