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Carpaine, a major alkaloid in papaya leaves, has considerable cardiovascular benefits alongside its notable effects on muscle relaxation when utilized in medicine. In this study, the coupling of acid-base extraction and flotation was developed to completely remove the use of toxic solvents. This method entails the extraction of carpaine from Carica papaya L. leaves using hot water extraction alongside ultrasound-assisted extraction followed by the condensation of the species using surfactant-assisted flotation. The acid-base extraction was applied to alter the solubility of carpaine as desired at different stages of the process. The results showed that the carpaine extraction yield using all the treatments in conjunction was significantly higher compared to the control samples in which the acid-base extraction or flotation was not applied. The TLC and GC-FID results suggested that the bubbles introduced during the flotation were highly specific toward their interactions with carpaine in its hydrophobic complex form. The quantity of carpaine extracted using our method, in comparison to the amount of carpaine obtained using a different method from a previous study that utilized ethanolic extraction, exhibited a 2.32-fold greater extraction yield. This work demonstrates the importance of flexible utilization of both surface and bulk chemistry in achieving an improved solution for a technical problem., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)