Preparation and in vitro dissolution behaviors evaluation of silymarin phospholipid complex / 药学实践与服务

Objective To prepare silymarin phospholipids complex（SM-PC） and investigate its physicochemical properties. Methods On the basis of single-factor tests, the drug-lipid ratio, drug concentration and reaction temperature were selected as the factors of the central composite design and response surface methodology in the preparation of SM-PC by solvent volatilization, and the best process was optimized with the compound rate as the index. And its in vitro dissolution was measured. Results The optimum preparation technology of SM-PC was as follows: acetone was used as compound solvent, the concentration of SM was 8.0 mg/ml, the mass ratio of SM to phospholipid was 1∶1.8, the reaction temperature was 56 ℃ and the recombination rate was（95.15±1.55）% with deviation of less than 3%. The in vitro dissolution test showed that the dissolution of SM-PC was close to 90% in 60 min. The dissolution behavior of main component of silybin was similar to that of silymarin capsules（Legalon ®）, which was higher than SM-API. Conclusion SM-PC was successfully prepared by central composite design response surface method, which significantly improved the dissolution and laid a foundation for the study of subsequent preparations.

Optimization of alcohol precipitation process for Quhan Zhufeng Granules by overall desirability and central composite design / 国际中医中药杂志

Objective:To optimize the alcohol precipitation process of Quhan Zhufeng Granules.Methods:Taking the volume fraction of ethanol, the relative density of the concentrated solution and the standing time as the investigation factors, the Z value of the total evaluation of gentiopicrin content, oleanolic acid content and dry paste yield of gentiana macrophylla as the evaluation indexes, the star-point design-response surface method was used to optimize the alcohol precipitation process.Results:The optimal the alcohol precipitation process of Quhan Zhufeng Granules: concentration relative density 1.08 g/ml (90-95 ℃), alcohol precipitation at the end of volume fraction of 62% ethanol, standing for 16 h.Conclusion:The alcohol precipitation process using overall desirability and central composite design is stable and feasible, and has good predictability, which can provide experimental basis for further scale production.

Study on Optimization of spray Drying Process of Banlangen Formula Granules / 世界科学技术-中医药现代化

Objective To optimize the spray drying process of Banlangen(Isatidis Radix)formula granules based on quality by design(QbD)concept.Methods Using powder yield and the contents of uridine,adenosine,guanosine,and(R,S)-goitron as the critical quality attributes(CQAs),Plackett-Burman design was used to screen out critical process parameters(CPPs)for inlet temperature,spray pressure,liquid temperature,pump speed,and liquid relative density.The central-composite design(CCD)test was used to optimize the CPPs,which were screened.Based on the quadratic polynomial regression model,the design space of spray drying process of Banlangen(Isatidis Radix)formula granules was established,and further validated by experiments.Results Plackett-burman test results show that liquid relative density and inlet velocity are the key parameters for the study.The variance analysis results of CCD test showed that the constructed model in a good prediction ability,since the P-values of model was less than 0.01 and P-values of items lack of fit was more than 0.05.The optimized design space of CPPs was the liquid relative density 1.05-1.08,and pump speed 30%-40%.Conclusion Based on the QbD concept,the design space for the spray drying process of Banlangen(Isatidis Radix)formula granules can improve the stability of its process and help ensure the consistency of product quality.

Preparation of Rubus parvifolius L.dispersible tablets and determination of its dissolution rate / 中国药师

Objective To optimize the preparation process of Rubus parvifolius L.dispersible tablets and determine its dissolution.Methods On the basis of single factor test,the formulation process of dispersible tablets was optimized by central composite design-response surface method with microcrystalline cellulose(MCC),polyvinyl polypyrrolidone(PVPP)and low substituted hydroxypropyl cellulose(L-HPC)as the influencing factors and disintegration time as the evaluation index.The total saponins of Rubus parvifolius L.was used as an indicator to determine the dissolution rate with reference to the method of Chinese Pharmacopoeia.Results The optimal prescription was 36.9％total saponin extract powder,42％MCC,13％PVPP,8％L-HPC and 0.1％microsilica gel,which showed a high correlation coefficient of the model.The disintegration time of the prepared dispersive tablets was less than 3 min,and the cumulative dissolution rate reached more than 88％at 50 min.Conclusion The optimized process is stable and reliable,and can be used for the preparation of Rubus parvifolius L.dispersible tablets.

Optimization of extraction process of prescription medicinal materials of compound Yangshe granules / 药学实践与服务

Objective Optimizing the extraction process of prescription medicinal materials of hospital preparation of compound Yangshe granules. Methods A high performance liquid chromatograph (HPLC) quantitative method was established for deacetyl asperulosidicacid methyl ester (DME) and ferulic acid (FC) of the active ingredient. Based on the content of DME, FC and the yield of extract, the extraction process of compound Yangshe granule extract was optimized using central composite design-response surface methodology. Results The established HPLC method of quantification of active components in compound Yangshe granules met the requirements of method validation. The optimal extraction process optimized by central composite design-response surface methodology were as follows: the weight of extraction solvent was 12 times of the medicinal slices, the alcohol concentration was 73% and the extraction time was 60 min. Conclusion In this study, the quantitative method of active components in compound Yangshe granule by HPLC has been successfully established, and the optimized extraction process is simple and easy to operate with good repeatability.

Optimization of the extraction process of Shangke Huoxue Granule by central composite design-response surface methodology / 国际中医中药杂志

Objective:To optimize the extraction process of Shangke Huoxue Granule.Methods:Taking the factors of extraction solvent multiple, extraction time and extraction times as investigation factors, and extraction amount of ferulic acid, paeoniflorin and the ratio of extraction as comprehensive evaluation indices, one-factor experimental design and central composite design-response surface methodology were adopted to optimize the extraction process of Shangke Huoxue Granule.Results:The binomial fitting equation was Y=96.16+2.42 A+0.63 B-3.76 AB-1.57 A2-1.87 B2 ( P<0.01). The optimal extraction process parameters were confirmed to be adding 16 times of water, 64 minutes each time, twice. The deviation rates between the measured values of three verification experiments and the predicted value were 2.00%, 3.23% and 0.66%. Conclusion:The established model of central composite design-response surface methodology has high predictability and the optimized extraction process is stable and feasible.

Preparation and quality evaluation of total flavonoids microemulsion of "Pueraria lobata-Hovenia dulcis" / 中国中药杂志

The effective components of flavonoids in the "Pueraria lobata-Hovenia dulcis" drug pair have low bioavailability in vivo due to their unstable characteristics. This study used microemulsions with amphoteric carrier properties to solve this problem. The study drew pseudo-ternary phase diagrams through titration compatibility experiments of the oil phase with emulsifiers and co-emulsifiers and screened the prescription composition of blank microemulsions. The study used average particle size and PDI as evaluation indicators, and the central composite design-response surface method(CCD-RSM) was used to optimize the prescription; high-dosage drug-loaded microemulsions were obtained, and their physicochemical properties, appearance, and stability were evaluated. The results showed that when ethyl butyrate was used as the oil phase, polysorbate 80(tween 80) as the surfactant, and anhydrous ethanol as the cosurfactant, the maximum microemulsion area was obtained. When the difference in results was small, K_(m )of 1∶4 was chosen to ensure the safety of the prescription. The prescription composition optimized by the CCD-RSM was ethyl butyrate(16.28%), tween 80(9.59%), and anhydrous ethanol(38.34%). When the dosage reached 3% of the system mass, the total flavonoid microemulsion prepared had a clear and transparent appearance, with average particle size, PDI, and potential of(74.25±1.58)nm, 0.277±0.043, and(-0.08±0.07) mV, respectively. The microemulsion was spherical and evenly distributed under transmission electron microscopy. The centrifugal stability and temperature stability were good, and there was no layering or demulsification phenomenon, which significantly improved the in vitro dissolution of total flavonoids.

Trametes versicolor (L.) Lloyd as a source of thermostable serine protease: production and characterization

Proteases are ubiquitously present and are among the largest groups of commercially important enzymes. Here, we investigated a wood-rot basidiomycete Trametes versicolor (L.) Lloyd [Syn. Coriolus versicolor (L.) Quél.; Polyporus versicolor (L.) Fr.] as a source of the enzyme serine protease, its production, and optimized to obtain a higher yield of the enzyme.. The significant variables with optimized values for maximum production of the enzyme were temperature (30?C), incubation time (120 h) and wheat bran (10 g). The yield increased by 30.76% by statistically optimizing the media. The optimized temperature and pH for the maximum protease activity was 50?C and pH 7.0, respectively. The enzyme was purified through ion exchange (using DEAE cellulose 52 resin) and gel filtration chromatography (using Superdex 200 column). The purified enzyme had a retention time of 7 min in RP-HPLC. The enzyme was stable at a broad range of temperature (30-60?C) and pH (5.0-8.0) with a half-life of 58.72 min, Vmax of 37.17 ?M min/mL and Km of 0.657 mg/mL. Its activity was enhanced by Na+, Ca2+, Mg2+ ions and SDS surfactant. These properties make this enzyme a valuable candidate for industrial applications

High protein, gluten-free cookies made with rice, beans and avocado

Cookies are versatile foods that can supply specific needs and can be used as food vehicles to increase the intake of various nutrients. The objective was to create a gluten-free butter cookie based on rice flour (Oryza sativa). A central composite design 22 was used for analyzing the substitution of rice flour for bean flour (Phaseolus vulgaris, L.) (0-60%) and the substitution of butter for avocado puree (Persea americana) (0-100%). Response Surface Methodology were used to analyze the data with a significance of 10% (p<0.1) and a minimum R2 of 0.6. Variables analyzed were protein content (%), fat content (%), spread ratio, weight loss (%), water activity, moisture content (%), and ash content (%). Increases in the percentage of substitution of bean flour and avocado puree increased the amount of protein, ash, and moisture significantly. Fat content increased significantly following the decrease in avocado substitution. The minimum weight loss was obtained on intermediate values of bean flour. Water activity and spread ratio were not affected by changes in the variables measured. Three different formulas were obtained for the optimization: 46% bean flour and 86% of avocado puree, a formulation with an appropriate moisture range by reducing the lipid oxidation (59% bean flour and 82% avocado puree), and a formulation with 100% avocado (40% bean flour and 100% avocado puree). Sensory evaluation results of optimized treatments indicated that the formula with 46% bean flour and 86% avocado puree presented the highest global acceptance. Results from this study showcase the possibility of producing gluten-free cookies with good protein content.

Las galletas son alimentos versátiles que pueden suplir necesidades específicas y ser utilizados como vehículos para aumentar la ingesta de distintos nutrientes. El objetivo fue elaborar galletas de mantequilla libres de gluten a base de harina de arroz. Se realizó un diseño central compuesto 22 donde se estudió la sustitución parcial de harina de arroz por harina de frijol (Phaseolus vulgaris, L.) (0-60%) y la sustitución de la mantequilla por puré de aguacate (Persea americana) (0-100%). Los resultados fueron analizados por la Metodología de Superficie de Respuesta con un nivel de significancia del 10% (p<0.1) y con un mínimo R2 de 0.6. Las variables de respuesta fueron: proteína (%), grasa (%), diámetro/altura, pérdida de peso (%), humedad (%) y cenizas (%). A valores altos de las dos variables estudiadas la cantidad de proteína, de cenizas y de humedad aumentó significativamente. La cantidad de grasa se incrementó al utilizar bajos niveles de puré de aguacate. Los menores valores de pérdida de peso se obtuvieron en niveles intermedios de harina de frijol. La relación diámetro/altura no fue afectada por las variables estudiadas. Al optimizar se obtuvieron 3 formulaciones diferentes: 46% de harina de frijol y 86% puré de aguacate; 59% de frijol y 82% de puré de aguacate y otra (no estadística) 40% de frijol y 100% de puré de aguacate. Los resultados del análisis sensorial de las muestras optimizadas indicaron que la formulación con mayor aceptación global fue la elaborada con 46% de harina de frijol y 86% de puré de aguacate, concluyendo que es posible elaborar una galleta libre de gluten y con una adecuada cantidad de proteína.

Preparation and in vitro evaluation of berberine hydrochloride nanoemulsion oral drug delivery systems / 药学实践杂志

Objective To prepare berberine hydrochloride nanoemulsion, optimize its formulation composition and preparation process, and investigate its in vitro characteristics. Methods BBR-NE was prepared by water drop addition and pseudo-ternary phase diagram was drawn. The formulation of NE was optimized by central composite design-response surface methodology to choose the optimal formulation composition. The particle size, potential and appearance of the prepared BBR-NE were characterized. Results The optimal prescription of BBR-NE was determined as the oil phase Capryol 90 accounted for 32.84% of the system, the surfactant Tween-80 accounted for 33.90%, the co-surfactant 1,2-propylene glycol accounted for 16.95%, and water relative system accounted for 15.25%. The prepared NE was clear and transparent in appearance, regular in shape and uniform in size, with an average particle diameter of (68.85±8) nm, polydiseperse index of (0.245±0.03) and drug loading of 0.83 mg/g. The in vitro drug release results of NE showed that the in vitro drug release behavior was passive diffusion, which had a certain slow releasing effect and met the first-order release equation. Conclusion The BBR-NE can provide a new dosage form for the clinical use of berberine.

Optimization of extraction technology of total saponins from Trillium tschonoskii Rhizome by response surface method / 国际中医中药杂志

Objective:To optimize the ethanol reflux extraction process of total saponins in total saponins of Trillium tschonoskii Rhizome. Methods:On the basis of single factor tests, making the total extraction rate of three main compounds [paris saponin Ⅵ, paris saponin Ⅶ and pennogenin-3- O-α-L-rhamnopyranosyl-(1→4)-[O-α-L-rhamnopyranosyl (1→2)]- O-β-D-glucopyranoside (PRRG)] as the indicator, the optimal extraction parameter was selected with the main influencing factors: the ethanol concentration, solid-liquid ratio, and extraction time by the central composite design-response surface method.Results:The optimal extraction parameter for the ethanol extract of total saponins of Trillium tschonoskii Rhizome was as follows: ethanol concentration 69%, extraction time 1.9 h, and solid liquid ratio 1∶9.7. The binomial fitting complex correlation coefficient r = 0.966 1, and the deviation between the extracted predicted value and the actual value is 4.68%. Conclusion:The central composite design-response surface method is simple and reliable for the optimization of extraction process of total saponins of Trillium tschonoskii Rhizome.

Optimization of stir-frying with saltwater technology of Citrus reticulate by entropy weight method combined with central composite design-response surface method / 中国药房

O BJECTIVE To optimize stir-frying with saltwater technology of Citrus reticulata . METHODS Taking the contents of limonin ，nomilin and obacunone ，color difference value and free radical scavenging rate of 1，1-diphenyl-2-trinitrophenyl hydrazine （DPPH） as the indexes ，the entropy weight method was used for comprehensive evaluation. The stir-frying with saltwater technology of C. reticulata was optimized by central composite design-response surface method by using water-salt ratio ，stewing time，frying temperature and frying time as factors. RESULTS The optimal stir-frying with saltwater technology of C. reticulata included water-salt ratio of 8 ∶ 1（mL/g），stewing time of 22 min，frying time of 9 min and frying temperature of 158 ℃. After three times of validation tests ，the average comprehensive score of the optimized technology was 92.35（RSD＝2.19％），and its relative error with the predicted value （93.25）was 1.10％. CONCLUSIONS The optimal stir-frying with saltwater technology is stable and feasible.

Content Determination of Pulegone in Schizonepeta tenuifolia and Its Compound Preparation by Hollow Fiber Liquid-phase Microextraction Coupled with HPLC / 中国药房

OBJECTIVE：To establish t he metho d for the content determination of pulegone in Schizonepetae tenuifolia decoction pieces and its compound preparation. METHODS ：Hollow fiber liquid-phase microextraction coupled with HPLC （HF-LPME-HPLC） was adopted. Based on single factor tests ，HF-LPME condition of S. tenuifolia decoction pieces and its compound preparation （taking Compound S. tenuifolia granule as an expample ） was optimized by central composite design-response surface methodology using pulegone enrichment multiple as index ，with the concentration of sample phase solution （NaCl），extraction time and stirring speed as factors. Validation test was conducted. HPLC method was adopted to determine the content of pulegone. The determination was performed on Hypersil C 18 column with mobile phase consisted of methanol- 0.3％ phosphoric acid （gradient elution ）at the flow rate of 1.0 mL/min. The detection wavelength was set at 252 nm，the column temperature was 25 ℃. The sample size was 20 μL. The feasibility of HF-LPME-HPLC method established in this study was validated by using HPLC method stated in the item of S. tenuifolia decoction pieces in 2020 edition of Chinese Pharmacopoeia （part Ⅰ）as reference. RESULTS ：The optimum HF-LPME conditions included n-nonanol as the extraction solvent ，sample phase solution with 11％ NaCl and pH value of 7，stirring speed of 800 r/min，extraction time of 36 min. Results of HPLC methodology investigation showed that linear range of pulegone were 0.05-5 μg/mL（r＝0.999 0）. The limits of detection and quantitation were 0.4 and 1.3 ng/mL，respectively. RSDs of intra-day and inter-day precision were 1.8％-4.0％ and 1.5％-4.1％（n＝3），respectively. RSDs of reproducibility and stability tests （24 h）were all lower than 8％（n＝6）. Average recoveries of S. tenuifolia decoction pieces and Compound S. tenuifolia granule were 102.6％-105.1％ and 97.2％-102.3％，respectively；RSDs were not higher than 4.1％ and 6.2％（n＝3）. The average contents of pulegone in S. tenuifolia decoction pieces determined by pharmacopoeia method and established method were 0.84 mg/g（RSD＝4.3％ ，n＝3）and 0.87 mg/g（RSD＝5.5％ ，n＝3），respectively，with no significant difference （P＞0.05）. CONCLUSIONS ：The established HF-LPME-HPLC method can enrich and concentrate pulegone ， shows strong purification ability and high sensitivity ，and can be used to determine the contents of pulegone in S. tenuifolia decoction pieces and its compound preparation.

Progress on application of central composite design-response surface methodology in optimization of preparations in China / 药学学报

Central composite design (CCD) is one of the most commonly used design methods in response surface optimization and has been widely applied in the field of pharmaceutics to optimize preparations. On the 20th anniversary of the introduction of CCD into China, the paper reviews its application in domestic pharmaceutical researches. Based on the brief introduction of basic principle and operation steps of CCD, the mistakes emerging in the application of CCD are summarized, including conceptual confusion with Box-Behnken design and face-centered CCD as well as wrong designs. Besides, the issues concerning the selection of factors and responses are discussed. The article is helpful for researchers to comprehensively understand the CCD and facilitates the rational application of this method.

Optimization of the matrix formulation of Erhuang analgesic gels by central composite design-response surface methodology / 国际中医中药杂志

Objective:To optimize the matrix formulation of Erhuang analgesic gels. Methods:Central composite design-response surface methodology was adopted to optimize the best formulation of Erhuang analgesic gels by using carbomer 940, triethanolamine and glycerine as independent variables, the appearance, stability, viscosity and in vitro release of berberine hydrochloride as comprehensive evaluation indices. Results:The fitting regressing equation was Y= 82.25 + 4.95 A+ 5.19 B + 1.41 C+ 1.51 AB + 0.904 0 AC- 0.531 9 BC- 2.92 A2-1.80 B2-0.182 1 C2. P value of the model was less than 0.000 1, and the correlation coefficient r value was 0.977. The optimal formulation of Erhuang analgesic gels consisted of 1.84% carbomer 940, 1.30 times triethanolamine of carbomer 940 and 13.99 grams of glycerine. The average comprehensive scores of three verification experiments was 88.56, and the deviations from the predicted values were 2.93%, 2.85% and 1.55%. Conclusion:The formulation process by central composite design-response surface methodology was stable and the formulation of Erhuang analgesic gels has been optimized.

Study on the optimization of the preparation technic and pharmacological activity of Chuanxiong Rhizoma / 国际中医中药杂志

Objective:To optimize the preparation technic of Chuanxiong Rhizoma with vacuum steam method, and to investigate the anti-inflammatory and analgesic activity of Chuanxiong Rhizoma decoction pieces with Central Composite Design-Response Surface Method. Methods:Taking the content of ferulic acid as the evaluation index and the moistening temperature, moistening time and vacuum time as the observation indexes, the moistening technic of Chuanxiong Rhizoma was optimized by Response Surface Method, and selected the optimized plan. The anti-inflammatory and analgesic activities of Chuanxiong Rhizoma were investigated by auricle swelling induced by xylene and writhing induced by glacial acetic acid. Results:The optimum vacuum moistening technic was that the softening temperature was 80 ℃, the softening time was 50 min and the vacuum time was 45 min. The content of ferulic acid in Chuanxiong Rhizoma produced by this technic is highand could decreased the times of wrinkle reaction induced by acetic acid in mice, prolonged the latent period, and obviously or partially inhibitied the ear swelling degree induced byxylene in rats. Conclusions:The Response Surface Method technic of Chuanxiong Rhizoma is easy to operate with high accuracy. The vacuum steam treatment was more obvious than traditional technology group. It provides reference for the subsequent production of Chuanxiong Rhizoma decoction pieces and have the certain value for its promotion and application.

Integrated

The drug formulation design of self-emulsifying drug delivery systems (SEDDS) often requires numerous experiments, which are time- and money-consuming. This research aimed to rationally design the SEDDS formulation by the integrated computational and experimental approaches. 4495 SEDDS formulation datasets were collected to predict the pseudo-ternary phase diagram by the machine learning methods. Random forest (RF) showed the best prediction performance with 91.3% for accuracy, 92.0% for sensitivity and 90.7% for specificity in 5-fold cross-validation. The pseudo-ternary phase diagrams of meloxicam SEDDS were experimentally developed to validate the RF prediction model and achieved an excellent prediction accuracy (89.51%). The central composite design (CCD) was used to screen the best ratio of oil-surfactant-cosurfactant. Finally, molecular dynamic (MD) simulation was used to investigate the molecular interaction between excipients and drugs, which revealed the diffusion behavior in water and the role of cosurfactants. In conclusion, this research combined machine learning, central composite design, molecular modeling and experimental approaches for rational SEDDS formulation design. The integrated computer methodology can decrease traditional drug formulation design works and bring new ideas for future drug formulation design.

Application Of Central Composite Design For Citalopram Hydrogen Bromide Mouth Dissolving Films

Citalopram is an antidepressant used for treating major depressive disorder. In the current work Citalopram HBr is formulated as mouth dissolving film with enhanced drug dissolution. The Central Composite Design (CCD), employed to examine the effects of amount of HPMC E50 (A), amount of maltodextrin (B) and amount of glycerol (C) on response variables tensile strength, disintegration time and cumulative % drug release. 27 formulations prepared according to CCD and evaluated for physicochemical parameters and in vitro dissolution studies. Citalopram HBr mouth dissolving films formulated by employing solvent-casting method using HPMC E50, maltodextrin and glycerol, optimized for the effective dosage of superdisintegrants. The formulation CF21 with maximum tensile strength of 67.21±1.31 gm, least disintegration time of 9±1.60 sec and highest drug release of 98.41±1.81% is chosen optimal formulation with maximum content uniformity and folding endurance. It is evident from the above results that the developed formulation can be an innovative dosage form to improve the drug delivery, quick onset of action as well as improve patient compliance in the effective management of depression.

Fabrication of potential gastroretentive microspheres of itraconazole for stomach-specific delivery: Statistical optimization and in vitro evaluation

The premise of the study was to develop and optimize multiple unit gastroretentive microspheres of itraconazoleto prolong its localization in the stomach and analyzed using response surface methodology. The emulsion solventdiffusion evaporation method was used to prepare hollow microsphere of ethyl cellulose and Eudragit RS100 as lowdensity shell-forming polymers. The experimental design matrix was prepared using a central composite design tostudy the effect of various process parameters over response variables. The optimized microspheres showed a particlesize of 285.1µm, drug entrapment efficiency of 86.8%, buoyancy of 51.1%, and cumulative drug release of 77.80%.The experimental responses were in good harmony with the predicted values. The compatibility between drug andexcipients was determined by Fourier-transform infrared and differential scanning calorimetry analysis. The resultssignify that gastroretentive hollow microspheres are a promising vehicle to extend the retention time of itraconazolein the upper GI tract, and it can be floated in an acidic medium for a prolonged period.

Optimized Aqueous Extraction Conditions for Maximal Phenolics, Flavonoids and Antioxidant Capacity from Artocarpus heterophyllus (Jackfruit) Leaves by Response Surface Methodology (RSM)

@#Introduction: There are numerous studies on the therapeutic properties of Artocarpus heterophyllus. However, studies on the aqueous extraction of A. heterophyllus leaves are limited. This present study was conducted to optimize the extraction conditions of A. heterophyllus leaves to yield the highest phenolic, flavonoids and antioxidant contents. Methods: Response surface methodology (RSM) was employed to obtain a higher phenolic extraction parameter(s) of A. heterophyllus leaves using Central Composite Design (CCD). The antioxidant activity was then determined via ABTS (2,29-azinobis (3 ethylbenzothiazoline-6-sulfonic acid)) and DPPH (2,2-Diphenyl-1-picrylhydrazyl) assay and analysis of the individual phenolics was performed by high performance liquid chromatography (HPLC). Results: The optimum extraction conditions with higher phenolics content and antioxidant activity was achieved at 81°C, 100 min and 40 mL/g sample with a good desirability value of 0.87. Under these optimized parameters, total phenolics and flavonoids were 174.48 ± 4.05 mg GAE/g sample and 21.44 ± 0.05 mg RE/g sample, respectively. Meanwhile, antioxidant activity via ABTS and DPPH assays were 90.88% ± 0.09 and 87.22% ± 0.62, respectively. Finally, under optimal extraction conditions revealed 4 compounds identified as chlorogenic acid, quercetin, rutin and kaempferol. Conclusion: The optimisation are promising to improve phenolic yield and antioxidant activity in A. heterophyllus leaves. It also proved that A. heterophyllus leaves can be used as an alternative natural antioxidant especially in medicinal applications since all identified compound possess significant biological activities for human health.