Drug transport mechanisms and in vitro release kinetics of vancomycin encapsulated chitosan-alginate polyelectrolyte microparticles as a controlled drug delivery system

Abstract

In this study, chitosan-alginate polyelectrolyte microparticles containing the antibiotic, vancomycin chloride were prepared using the ionotropic gelation (coacervation) technique. In vitro release and drug transport mechanisms were studied concerning the chitosan only and alginate only microparticles as a control group. Further, the effect of porosity on the drug transport mechanism was also studied for chitosan-alginate mixed particles produced by lyophilizing in contrast to the air-dried non-porous particles. According to the in vitro release data, alginate only and chitosan only microparticles showed burst release and prolonged release respectively. Chitosan-alginate lyophilized microparticles showed the best-controlled release of vancomycin with the average release of 22μg per day for 14days. Also, when increasing alginate concentration there was no increase in the release rate of vancomycin. The release data of all the microparticles were treated with Ritger-Peppas, Higuchi, Peppas-Sahlin, zero-order, and first-order kinetic models. The best fit was observed with Peppas-Sahlin model, indicating the drug transport mechanism was controlled by both Fickian diffusion and case II relaxations. Also, Fickian diffusion dominates the drug transport mechanism of all air-dried samples during the study period. However, the Fickian contribution was gradually reducing with time. Porosity significantly effects the drug transport mechanism as case II relaxation dominates after day 10 of the lyophilized microparticles.

Keywords: Alginate; Chitosan; Lyophilizing; Polyelectrolyte; Transport mechanism.

Figure 1

Mechanism of drug release from particulate system

Figure 2

Schematic representation of CS-AL MP preparation and appearance of the MPs at low and high magnification

Figure 3

SEM micrographs; rows (I)- CS only, (II)- AL only, (III)- CS-1%AL, (IV)- CS-2%AL, (V)- CS-1%AL LP; columns Magnification (A)- X 50, (B)- X 2000, (C)- X 200 cross section

Figure 4

FTIR spectra of CS, AL, vancomycin and vancomycin loaded MPs as indicated

Figure 5

Swelling ratio of MPs from day 1 to day 21; significance of p<0.05, * and ** represent significance difference with respect to other four sample groups; n=3

Figure 6

Cumulative drug release percentage with respected to total encapsulated drug amount; n=3

Figure 7

Fractional drug release from different MPs. Experimental data points and predicted data from E (4) - Ritger-Peppas model; symbols- represent the experimental data, solid lines- represent the predicted model; n=3

Figure 8

Fractional drug release from different MPs. Experimental data points and predicted data from Eq. (5) - Higuchi model; symbols- experimental data, solid lines- represent the predicted model; n=3

Figure 9

Fractional drug release from different MPs. Experimental data points and predicted data from Eq. (6) – Peppas-Sahlin model; symbols- represent the experimental data, solid line- represent the predicted model; n=3

Figure 10

Fractional drug release from different MPs. Experimental data points and predicted data from Eq. (7) – Zero order model; symbols- represent experimental data, solid line- represents the predicted model; n=3

Figure 11

Fractional drug release from different MPs. Experimental data points and predicted data from Eq. (8) – First order model; symbols- represent experimental data, solid line- represents the predicted model; n=3

Figure 12

Relaxation contribution (R)/Fickian Contribution (F) ratio with respect to time