Study On Drug Release Behavior And Drug Status Within Curcumin-loaded Sustained Release Microspheres

Objective: In order to prepare the curcumin-loaded sustained release microspheres with SPG membrane emulsification. And then drug release behaviors of different drug loading microspheres were studied to comprehend the mechanism of drug release. Furthermore, the drug status within different drug loading microspheres was investigated to expound the discrepancy between the drug release behaviors of different drug loading microspheres. Methods: SPG(shirasu porous glass) membrane emulsification was adopted to prepare the curcumin-loaded sustained release microspheres, with polylactic-co-glycolic acid(PLGA) as the carrier material. The drug loading, encapsulation efficiency and morphology were chosen as the indexes to evaluate the influence of four factors to the properties of microspheres, including the proportion of organic phase, viscosity of PLGA, concentration of polyvinyl alcohol(PVA) solution and the stirring time after dilution. After that, the high, medium and low drug loading microspheres were prepared by changing the dosage of curcumin. And the drug release behaviors of the three batches of microspheres were studied with the high performance liquid chromatography(HPLC). In vitro release data obtained were then fitted according to zero-order kinetics, first-order kinetics, Higuchi equation and biexponential and biphase kinetics with Origin software respectively, in order to comprehend the mechanism of drug release. Scanning electron microscope(SEM) was used to observe the morphology of different drug loading microspheres. Furthermore, the curcumin status within three groups of microspheres was investigated with X-ray diffraction(XRD), differential scanning calorimetry(DSC) and infrared analysis(IR), and then its effects to the drug release behaviors of microspheres were evaluated. Results: According to the results obtained, the ratio of methylene chloride and ethyl acetate was determined as 4∶3, the viscosity of PLGA was 0.41dl·g-1, the concentration of PVA solution was 1%, and the stirring time after dilution was 3h. The drug loading of microspheres prepared as the optimal formulation could reach 15.37%, the encapsulation efficiency was 91.78%, and the microspheres did not stick with each other. Drug loading of the microspheres obtained by changing the curcumin dosage was(5.85±0.21)%、(11.71±0.39)%、(15.41±0.40)%, and encapsulation efficiency was(92.34±1.36)%、(97.46±3.52)%、(91.29±3.07)%. The in vitro release results showed that all of the three kinds of microspheres had a good sustained release effect. During the 120 hours, the proportion of curcumin released by three kinds of microspheres was 65.05%, 79.51% and 88.36% respectively, while the proportion of the first 5 hours was 19.68%, 27.44% and 41.05%. The drug release behaviors were all in line with the biexponential and biphase kinetics model. The results of SEM showed that no curcumin crystals adsorbed on the surface of microspheres. The particle size of three kinds of microspheres was 69.034、74.281 and 77.360μm. And the results of IR indicated that, the hydrogen bonds formed between portions of curcumin and PLGA, but no new materials generated from chemical reaction. Inside the microspheres of lowest drug loading, curcumin dispersed in PLGA as amorphous form completely, while(2.12±0.64)% and(5.66±0.07)% curcumin crystals was detected in the other two kinds of microspheres respectively, and the proportion of the curcumin of amorphous form was 9.59% and 9.75%.Conclusion: When the content was less than 10%, curcumin would transform to amorphous form completely, and dispersed in PLGA; When the content was higher than 10%, the exceeding part of curcumin would exist as the form of crystals inside the microspheres independently. This part of curcumin was easier to be released from microspheres. What’s more, the crystalline curcumin might be able to make the structure of microsphere a little looser. As a result, higher the drug loading of microspheres was, the burst effect was usually more severe, and the overall drug release rate was faster. In conclusion, the drug status within microspheres of different drug loading was different from each other, and which would affect the drug release behavior obviously.