Studies On Preparations And Drug Releasing Properties Of Levodopa-Chitosan Drug-loading Microparticles

According to the principle of inversed phase emulsification and ionic crosslinking,levodopa (LDP)-chitosan (CS) microparticles were prepared, by using CS aspolymeric carrier, sodium tripolyphosphate (TPP) as ionic crosslinking reagent, andLDP as modeldrug. The shapes and sizes of the microparticles were reviewed byoptical microscope, polarizing microscope and laser particle analyzer. Thephysicochemical properties of the microparticles were characterized by FT-IR, DSC,TG, and XRD analyses. The drug-releasing performances of the microparticles wereinvestigated by UV-VIS analyses and in vitro release tests. A series of studies andresults are as follows:The chemical and physical properties of LDP were tested, and the feasibility ofcoating LDP with polymers was discussed. The results indicate that LDP can beoxidized by air or other oxidant, and the oxydation can be accelerated by light or base.Crystals of LDP are chemical stable, while their water solution is unstable. LDP canbe stably dissolved in CS-acetic acid solution or SALG solution, however, it will beoxidized rapidly in SCMC solution because of the basic media. Aldehyde can reactwith LDP, while polyvalent anion and Ca²⁺ can not. The FT-IR spectra LDP has anintricate fingerprint region, DSC and TG curves show the melting point of LDP, XRDanalysis indicates a high crystallinity of LDP, the absorption peak of LDP at UV280nm can be a standard for its quantitative analysis.Microparticles, such as CaCl₂/ALG microspheres, TPP/CS microspheres, citricacid/CS microspheres, CS/ALG microcapsules, and ALG/CS microcapsules, wereprepared, and their shapes, dispersivities as well as stabilities were compared. Theresults suggest that only TPP/CS microspheres ate suited to be the carrier particles forLDP. The optimized processing conditions of TPP/CS microspheres are as follows:water/oil ratio is 1/5, mixing speed is 600r/min, the proportion of Tween-80 is 1%,while Span-80 4%, n(TPP)/n(-NH₂)=1/1.5, room temperature is needed, and thecrosslinking time is 1.5h. FT-IR analyses prove that TPP/CS microspheres were formed through an electrostatic interaction between the protonated amino groups ofCS and TPP. DSC and TG analyses indicate that after CS combines with TPP,decomposition temperature of CS drops down because of the broken of hydrogenbonds. XRD analyses show the fact that the crystallinity of CS is lower when CScombines with TPP.LDP-CS microparticles were prepared, by using TPP as ionic crosslinking reagent.The polarizing microscope graph shows that, the particles so prepared are basicallyspheric. The average diameter of the microspheres detected by laser particle analyzeris about 3.5μm. FT-IR spectrums indicate that levodopa is enwrapped in chitosanmicrospheres. Levodopa crystals in the microspheres are detected by DCS and TGanalyses. CS combined with water through hydrogen bond when the microspheresformed. The drug-loading rates, drug-trapping efficiencies, and drug-releasingperformances of the microspheres are affected by the processing conditions, such asCS concentrations, drug/carrier ratios, dosages of TPP and pH values of cross-linkingmedia. The drug-releasing performances of the microspheres are further affected bythe pH values of the releasing media. In acid media, the microspheres show gooddrug-releasing performances, while the releases of drug are faster and morecompletely in basic media.