Preparation of cross-linked chitosan microspheres by spray drying: Effect of cross-linking agent on the properties of spray dried microspheres

Abstract

Chitosan microspheres cross-linked with three different cross-linking agents viz, tripolyphosphate (TPP), formaldehyde (FA) and gluteraldehyde (GA) have been prepared by spray drying technique. The influence of these cross-linking agents on the properties of spray dried chitosan microspheres was extensively investigated. The particle size and encapsulation efficiencies of thus prepared chitosan microspheres ranged mainly between 4.1-4.7 microm and 95.12-99.17%, respectively. Surface morphology, % erosion, % water uptake and drug release properties of the spray dried chitosan microspheres was remarkably influenced by the type (chemical or ionic) and extent (1 or 2% w/w) of cross-linking agents. Spray dried chitosan microspheres cross-linked with TPP exhibited higher swelling capacity, % water uptake, % erosion and drug release rate at both the cross-linking extent (1 and 2% w/w) when compared to those cross-linked with FA and GA. The sphericity and surface smoothness of the spray dried chitosan microspheres was lost when the cross-linking extent was increased from 1 to 2% w/w. Release rate of the drug from spray dried chitosan microspheres decreased when the cross-linking extent was increased from 1 to 2% w/w. The physical state of the drug in chitosan-TPP, chitosan-FA and chitosan-GA matrices was confirmed by the X-ray diffraction (XRD) study and found that the drug remains in a crystalline state even after its encapsulation. Release of the drug from chitosan-TPP, chitosan-FA and chitosan-GA matrices followed Fick's law of diffusion.

Imobilização da lacase em micropartículas de quitosana obtidas por spray drying e usadas na construção de biossensores

“…Micropartículas com tamanho e morfologia similares foram reportadas por Desay e Park. 40 O processo de reticulação da quitosana é de grande importância, pois, além de promover a formação de uma rede polimérica na qual a enzima pode estar covalentemente ligada e/ou entrapeada, previne o intumescimento das micropartículas de quitosana em soluções aquosas, 41 favorecendo uma maior estabilidade da enzima imobilizada.…”

“…39,40 Esse comportamento foi comprovado por alguns pesquisadores, 39,40 que realizaram estudos sistemáticos variando a concentração deste agente de reticulação e verificaram que micropartículas de quitosana reticuladas com TPP em excesso, obtidas por spray drying, apresentaram morfologia similar às apresentadas neste trabalho.…”

pH-sensitive polyvinylpyrrolidone-acrylic acid hydrogels: Impact of material parameters on swelling and drug release

“…Concerning point "b", by increasing cross-linking agent there is an increase in the number of links between two cross-links that leads to a decrease in porosity (see table III), leading to a decrease in loading efficiency. Desai et al prepared chitosan microspheres by using three different cross-linkers and found a decrease in encapsulation when increasing cross-linker concentration from 1% to 2% (Desai, Park, 2005). Effect of pH on drug release was investigated by obtaining dissolution profiles at various pH such as 1.2, 5.5 and 7.5.…”

Preparation, in vitro characterization, pharmacokinetic, and pharmacodynamic evaluation of chitosan-based plumbagin microspheres in mice bearing B16F1 melanoma

“…In addition, cross-linking of the chitosan can potentially influence the release pattern of the loaded drug. Glutaraldehyde is reported as the best cross-linking agent for various classes of drugs (Desai & Park, 2005). Hence, in the present study, glutaraldehyde was used as a cross-linking agent.…”