Andrographolide (AGP), a major component of Andrographis paniculata (Burm.f.) Nees (AP), has several biological activities. Nevertheless, poorly water solubility and low bioavailability of AGP lead to decrease clinical benefits. Therefore, this study aims to develop of AP extract-chitosan solid dispersion using central composite design (CCD) to enhance AGP release. AP crude extract was obtained by Soxhlet extractor using 85%v/v ethanol as a solvent extraction. Then, AP extract, chitosan, and poloxamer 188 in the concentrations provided by CCD was spray dried. The in-vitro release of AP extract-chitosan spray dried powder was studied by dissolution equipped with enhancer cell in 200 ml of 50%v/v methanol at 37°C and 50 rpm of paddle speed. Samples were withdrawn at 0.25-96 hours and then determined AGP by UV spectrophotometer at 224 nm. The results of CCD indicated that %ethanol and %AGP from concentrated AP extract had significant (P < 0.05) effect on the concentration of AGP released at 5 hours. The optimum formulation composed of %ethanol of 18.25, %AGP in extract of 0.38, and %poloxamer 188 of 0.17 resulted in more AGP concentration at 5 hours than 50 μg/mL. Release kinetic study revealed that %release of the optimal formulation was best fitted to first order kinetic. In powder X-ray diffraction, intensity of AGP characteristic peaks in the optimal formulation decreased by 7.17-25.69 times compared with AGP standard. It was concluded that the optimal formulation of AP extract-chitosan solid dispersion could improve AGP release due to changing crystalline AGP to amorphous state.