Applied Pharmacology and Pharmaceutical Technology (APPT) Research Article ISSN x-x Optimization of Ultrasonic Assisted Extraction Method for the Extraction of Quercetin from Malus domestica Yovi GuanseA* A Universitas 17 Agustus 1945 Jakarta. Jakarta Utara. Indonesia, 14350 *Corresponding author: yovi. guanse@uta45jakarta. *Submitted: 18/02/2026 *Accepted: 22/02/2026 *Published: 23/02/2026 Abstract This study optimized ultrasound-assisted extraction (UAE) of quercetin from Malus domestica . ed apple. using central composite design, targeting ethanol-in-water concentration . 7Ae98. 3%) and sonication time . 8Ae51. 2 mi. Quercetin was quantified by UV-Vis at 372 nm, with response surface methodology yielding a significant quadratic model . <0. Higher ethanol concentrations coupled with shorter sonication durations maximized quercetin extraction yields, as confirmed by ANOVA with the most influential factor was ethanol concentration (F = 38. Keywords: Malus domestica. Ultrasound-Assisted Extraction. Central Composite Design. ANOVA. Introduction Indonesia, a tropical nation renowned for its abundant natural resources, extensively cultivates apples (Malus domestic. According to data from the Central Bureau of Statistics . , annual apple production reached 392,563 tons in 2023. Apples are rich in bioactive compounds, including flavonoids, specifically quercetin . The plentiful availability of apples in Indonesia presents a substantial opportunity to harness them as a source of active ingredients for developing natural product-based formulations. Quercetin, a ubiquitous flavonoid abundant in various vegetables and fruits, has gained prominence in recent topical cosmetic formulations due to its multifaceted pharmacological properties. It exhibits potent antioxidant activity through free radical scavenging and modulation of oxidative stress pathways, alongside anti-inflammatory effects via inhibition of pro-inflammatory cytokines such as TNF- and NF-B signaling. Additionally, quercetin demonstrates selective antibacterial action against acne-causing pathogens like Propionibacterium acnes and Staphylococcus epidermidis, making it particularly valuable for acne management. In topical preparations, nanoemulsion or liposomal delivery systems enhance its poor aqueous solubility, dermal penetration, skin barrier function, erythema reduction, and wound healing . Ae. Guanse, 2026 Optimization of Ultrasonic Assisted Extraction Method for the Extraction of Quercetin from Malus domestica Applied Pharmacology and Pharmaceutical Technology (APPT) Research Article ISSN x-x Ultrasound-assisted extraction (UAE) is an advanced, green extraction technique that utilizes high-frequency ultrasonic waves to induce acoustic cavitation, facilitating efficient release of bioactive compounds from plant matrices through enhanced mass transfer, cell disruption, and solvent penetration . Prior research indicates that the quantity of extracted natural compounds is markedly affected by sonication time and solvent concentration . Zakaria et al. optimized UAE of Mitragyna speciosa leaves, demonstrating that sonication duration extension from 15 to 50 min boosted yield from 18% to 27. 88% through enhanced cavitation, while solvent concentration influenced solubility matching . Wang et al. reviewed UAE of bioactive compounds from Muxu (Medicago sativ. , reporting optimal flavonoid yields at 30 min sonication with 1:30 solid-liquid ratios and 50AC, where prolonged times beyond optimal reduced efficiency due to degradation, and solvent ratios modulated extraction rates . This study aims to determine the optimal sonication time and ethanol concentration conditions to achieve maximum quercetin extraction yield from natural sources. Response Surface Methodology, specifically Central Composite Design was selected to systematically investigate the interactive effects of sonication duration and ethanol concentration on the resultant quercetin concentration. This approach enables precise modeling of the extraction process, facilitating identification of the most efficient parameter combinations for pharmaceutical formulation applications Materials and Method Materials The instrument used in this study included a UV-Vis spectrophotometer (Shimadzu UV mini-1. , a laptop (Acer Aspire . equipped with Design ExpertA 13 software, ultrasonication (Branson 3. , centrifuge, and glassware. The materials used were red apples (Malus domestic. , ethanol, and aquadest. Methods Ultrasound-Assisted Extraction Ultrasound-assisted extractions were conducted using a ultrasonication (Branson 3. operating at 40 kHz and 100 W nominal power, 1 gram of red apples powder was suspended in solvent mixtures . arying proportion. Independent variables, including ethanol and sonication time were optimized, with extractions followed by centrifugation . 0yg, 5 mi. The central composite design extraction scheme is presented in the following table: Guanse, 2026 Optimization of Ultrasonic Assisted Extraction Method for the Extraction of Quercetin from Malus domestica Applied Pharmacology and Pharmaceutical Technology (APPT) Research Article ISSN x-x Independent Variable X1: Ethanol in X2: Sonication Time Table 1. Central composite design extraction scheme Coded Levels Unit Axial (-) Low Centre High Axial ( ) Analysis of the Quercetin by Spectrophotometer UV-Vis Quercetin standard stock solution . was serially diluted to prepare calibration standards at 20, 30, 40, 50, and 60 ppm. the absorption of the extracted sample solution, consisted of Malus domestica extract determined using Spectrophotometer UV Vis at 372 nm . Experimental Design The Central Composite Design was used to determine the optimal extraction conditions. For this purpose, 2 factors were considered, representing the independent variables at different levels. The independent variables were % ethanol in water (X. , and sonication time (X. A total of thirteen experiments were derived from CCD through Design Expert 13 software. The response variables were total quercetin concentration which represent the concentrations of the majority compounds in the Malus domestica samples quantified by spectrophotometry UV-Vis. A polynomial equation (Equation . was generated to predict the correlation between the independent variables and the response. yco yco yco yc = yu0 Oc yuycn ycUycn Oc yuycnycn ycUycn2 Oc Oc yuycnyc ycUycn ycUyc ycn=1 ycn=1 . ycn 0. were retained in the final reduced model when associated quadratic or interaction terms were significant . < 0. Model Equation p-value Table 2. Equation and p-value for the final reduced model Value Y= 0. 131155ycU1 Oe 0. 0587548ycU2 0. 011ycU1 ycU2 Oe 0. 0254875 ycU12 Oe 0532375ycU22 <0. Analysis of variance (ANOVA) was conducted to evaluate the significance of the quadratic polynomial models (Table . The elevated F-values and low p-values . < 0. for all main effects confirmed their significant effects on the response variables. Results indicated that ethanol concentration and sonication time exerted positive influences on quercetin concentration. Two-dimensional response surface plots depicting the interplay between ethanol concentration and sonication time provided further insight into the factor interactions (Figure . Table 3. ANOVA of regression coefficient of the fitted quadratic equation for UAE Variables Quercetin Concentration F value p-value Main Effects Quadratic Effects Interaction Effect Identifying the optimal combination of sonication time and ethanol-in-water concentration is crucial, as elevated quercetin concentrations were observed with increasing ethanol-in-water levels and decreasing sonication time. The most influential factor was ethanol concentration, with an F-value of 38. Thus, extractions yielding high quercetin concentrations can be achieved using high ethanol concentrations and short sonication durations. Guanse, 2026 Optimization of Ultrasonic Assisted Extraction Method for the Extraction of Quercetin from Malus domestica Applied Pharmacology and Pharmaceutical Technology (APPT) Research Article ISSN x-x Figure 1. Response surface plots showing the effect of interaction between sonication time . and ethanol concentration (%) on quercetin concentration (%) Conclusion The central composite design successfully optimized ultrasound-assisted extraction of quercetin from Malus domestica, revealing that elevated ethanol-in-water concentrations combined with reduced sonication times significantly quercetin concentration. This green UAE approach offers a reproducible, efficient method for isolating quercetin. Future studies could validate these conditions at pilot scale and explore additional factors such as temperature, cycle, amplitude, and sample-to-solvent ratio. Conflict of Interest Statement The authors declare no conflict of interest related to this work. References