Characterization and in vitro release study of artesunateloaded microparticles prepared using crosslinked-chitosan and its derivatives

Retno Sari,Andang Miatmoko,Meta Dian Feriza,Dwi Setyawan,Amani Syarahil

doi:10.4314/tjpr.v19i6.3

Abstract

Purpose: To determine the effect of crosslinking on the physical characteristics, recovery, and release of artesunate-loaded chitosan and carboxymethyl chitosan microparticles.Methods: The artesunate microparticles were prepared by means of ionic gelation-spray drying methods involving the use of a crosslinking agent i.e. tripolyphosphate for chitosan and CaCl2 for carboxymethyl chitosan. The drug-polymer solution mixture was introduced into the crosslinker solution and stirred for two hours at 500 rpm prior to drying at a temperature of 100ºC, a pressure of 2 mbar and a flow speed of 6.0 mL/min. The resulting microparticles were subsequently evaluated for their morphology, physical state, drug content and in vitro drug release.Results: The results showed that the type of chitosan and crosslinking affected particle shape, surface roughness, drug recovery, and drug release. The artesunate microparticles prepared with cross-linked polymer demonstrated a lower encapsulation efficiency due to the barriers presented by the crosslinking agents. The use of carboxymethyl chitosan increased the release rate of the artesunate from the microparticles by up to 1.2 times (16.78 mg/ml.min½), while chitosan decreased it 0.7 times (9.12 mg/ml.min½) compared to artesunate alone (13.54 mg/ml.min½).Conclusion: The use of crosslinking agents and chitosan type affects the physical characteristics of artesunate in addition to its release rate from microparticles. Keywords: Artesunate, Chitosan, Carboxymethyl chitosan, Crosslinking, Microparticle, Drug release

Highlights

Artesunate, an artemisinin derivate, constitutes an antimalarial drug effective against Plasmodium falciparum, even in cases of chloroquine-resistant parasites [1], but which demonstrates low drug solubility resulting in extremely limited drug bioavailability when administered orally
In the course of this study, it has been shown that the type of chitosan polymers and the presence of crosslinking agents affected the surface morphology of artesunate microparticles (Figure 1 A - D)
The CM-CL-AS and CM-AS bands were in sharper relief than those of carboxymethyl chitosan and a shift could be observed indicating that the -OH, -NH, and -COO groups are involved in bond formation within the microparticles

Summary

Introduction

Artesunate, an artemisinin derivate, constitutes an antimalarial drug effective against Plasmodium falciparum, even in cases of chloroquine-resistant parasites [1], but which demonstrates low drug solubility resulting in extremely limited drug bioavailability when administered orally. Chitosan is a natural cationic polysaccharide polymer widely employed to prepare microparticles, useful in modifying the solubility and stability of a drug. It provides certain ideal properties for drug carriers, such as mucoadhesiveness, biocompatibility, biodegradability, non-toxicity, and economy. Carboxymethyl chitosan, a derivate of chitosan, has recently been developed since it possesses high aqueous solubility, strong gelforming capacity, low toxicity, and high levels of biocompatibility [8]

Results

Discussion

Conclusion