The primary objective of the proposed research work is to extract and enrich pure andrographolide(AGL) by varying the polarity index and Hildebrand solubility parameter (δ) of a moderatelypolar solvent. Both parameters affect the solubility of AGL in different solvents and extractionmethods.AGL was extracted from the whole plant Andrographis paniculata. Continuous or Direct,Maceration and Soxhlet extraction method used for extraction. Based on the appearance of thecrystal in the direct Soxhlet ethyl acetate method, their yield was further optimized by using arandomized response surface methodology (RSM) and quadratic model-based Box‒Behnkendesign (BBD). HPTLC was used to determine the AGL extraction efficiency, purity, andquantification. Based on the obtained result, the pure andrographolide crystal (yield 0.185 g/g)was obtained by direct Soxhlet extraction. Ethyl acetate is used as a solvent. The Rf exhibitedin the TLC chromatogram was 0.28. The FT-IR spectra exhibited characteristic peaks similarto the standard AGL, and 1H-NMR and 13C NMR elucidated the crystal structure. The DEPT-90/135 spectra showed that the extracted crystal was pure AGL. One of the novel approachesis isolating pure AGL crystals in a moderately polar solvent (ethyl acetate) by elevating theHildebrand solubility parameter despite using polar solvents. AGL crystals were obtained fromdirect Soxhlet extraction by ethyl acetate.It is a single-step and more economical method. It can be easily transformed into a pilot orindustrial setup to extract the pure AGL.

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The primary objective of the proposed research work is to extract and enrich pure andrographolide (AGL) by varying the polarity index and Hildebrand solubility parameter (δ) of a moderately polar solvent. Both parameters affect the solubility of AGL in different solvents and extraction methods. AGL was extracted from the whole plant Andrographis paniculata. Continuous or Direct, Maceration and Soxhlet extraction method used for extraction. Based on the appearance of the crystal in the direct Soxhlet ethyl acetate method, their yield was further optimized by using a randomized response surface (RSM) and quadratic model-based Box‒Behnken design (BBD). HPTLC was used to determine the AGL extraction efficiency, purity, and quantification. Based on the obtained result, the pure andrographolide crystal (yield 0.185 g/g) was obtained by direct Soxhlet extraction. Ethyl acetate is used as a solvent. The Rf exhibited in the TLC chromatogram was 0.28. The FT-IR spectra exhibited characteristic peaks similar to the standard AGL, and 1H-NMR and 13C NMR elucidated the crystal structure. The DEPT − 90/135 spectra showed that the extracted crystal was pure AGL. One of the novel approaches is isolating pure AGL crystals in a moderately polar solvent (ethyl acetate) by elevating the Hildebrand solubility parameter despite using polar solvents. AGL crystals were obtained from direct Soxhlet extraction by ethyl acetate. It is a single-step and more economical method. It can be easily transformed into a pilot or industrial setup to extract the pure AGL.