Results and Discussions Optimization of the Acid Catalyst Concentration for Synthesis of Anti‐Cancer Agent Gamavuton‐0 by Using Mathematical and Statistical Software

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Figure . TLC of GVT‐ yellow and vanillin purple as the standard The GVT‐O obtained from the synthesis at varying Cl concentration was arranged in Table . Table . Obtained GVT‐ from the synthesis Sample Vary of Cl concentration ppm GVT‐O g Average g . . . . . . 8 . . . 8 8 . . . Table is the ANOVA result of the obtained data from the experiment. ANOVA was conducted to determine the variation of the data. The significant variation of the data can be evaluated from the P‐value. The P‐value indicates the significance of the relationship between independent parameter and the response variable Daneshvar, . Based on the ANOVA results, there is significant difference between the data that has been obtained. The significant difference can be identified from the P‐value generated from the analysis, i.e. . P‐value . This result is less than the acceptable quality level AQL of ANOVA that was set up at P‐value of . . That means there is a significant relationship between the variations of acid catalyst concentration and GVT‐O produced. n the other word, by changing the acid concentration significantly change the GVT‐ produced. Table . Result of analysis of variance ANOVA Source Sum of squares df Mean square F‐Ratio P‐value Model . 8 . 8 . 0.0633 Residual . 8 Total Corr. . Regression analysis was chosen as a method for hypothesis testing based on its ability to measure of the strength of the relationship between the response variable and the predictor variables, determine the influence of one or several variables predictors of response variables, and was useful for predicting the effect of a variable or multiple response variables riawan and Astuti, . 2 0 Figure . Plot of catalyst concentration vs GVT‐O R‐squared = . 88 percent; R‐squared adjusted for df. = 8. Correlation of the acid catalyst concentration X and the GVT‐ produced Y can be plotted as shown in Figure . The R‐Squared value of the plot data was found to be . 88 , means that the GVT‐ produced following the mathematical model generated very well. The analysis using regression polynomial second order gave an equation as expressed as Equation . The use of the equation is for predicting the GVT‐O produced once the concentration of catalyst is known at the experiment set up as mentioned above. When the Equation assumed to be Y = aX +bX+c, the highest value of Y will be reached when the value of X = –b a. Based on the Equation , calculation of the optimum value of X was found to be . 8 ppm. Y = ‐ . X + . 8X ‐ . Figure shows that by increasing the catalyst concentration increase the GVT‐O produced. At the optimum concentration of catalyst, the GVT‐O produced was the highest one, this may due to at the optimum concentration the fastest reaction rate was occurred. Still increase the catalyst concentration at ppm and 8 ppm, the rate of the reaction decreasing. The decrease of the rate of reaction can be detected by reducing the GVT‐ produced. Equation can be used to predict the theoretical amount of GVT‐ produced once the acid catalyst concentration is known. By using Equation , GVT‐ predicted at optimum acid catalyst concentration of . 8 was found to be . grams. The calculation process can be conducted as follows: Y = ‐ . X + . 8X ‐ . Y = ‐ . . 8 + . 8 . 8 ‐ . Y = , gram predicted Validation of the equation can be conducted by carrying out an experiment using a theoretical condition suggested. During the experiment using . 8 ppm of acid catalyst concentration, the GVT‐ produced was . grams. The comparison between the predicted to the experimental results can be seen in Figure . 2 1 The difference between predicted and experiment of GVT‐O produced can be calculated using Equation . The difference of GVT‐ produced is . . This indicates that the equations obtained can be used to predict the number of GVT‐ desired when the acid catalyst concentration is known. This data will be very useful for further optimization process on finding the other optimum condition of parameter during the synthesis. Surely, this result will be very useful in proposing of production in the industry with larger scale. Conclusion Based on the experimental results, by using mathematical and statistic software the experiment was more efficient and the best acid catalyst concentration was found to be ppm at the setup of experimental condition. Acknowledgements The financial and facility support to the author from Universitas Muhammadiyah Yogyakarta is highly acknowledged. References Agrawal D.K., Mishra P. K.., . Curcumin and its analogues: potential anticancer agents. Med Res Rev. Sep; :8 8‐ .doi: . med. 88. http:www.ncbi.nlm.nih.govpubmed 8 . Accesed on nd May . Daneshvar, N., Behnajady, M. A., Asghar, Y. Z., . Photooxidative Degradation of ‐ nitrophenol ‐NP in UV O Process: nfluence of Operational Parameters and Reaction Mechanism, J. Hazard. Mater., vol. B , p. ‐ Fahrurozi, 8 . The influence of mole concentration of reactant on the gamavuton‐ synthesis using ethanol as the solvent and cytotoxic test toward e La cell, Final year project, Pengaruh jumlah mol pereaksi pada sintesis senyawa gamavuton‐0 dengan pelarut etanol 2 2 dan uji sitotoksik terhadap sel HeLa , Final year project Skripsi , Universitas Gadjah Mada, Yogyakarta. Fessenden, R.J., and Fessenden, J.S., . Organic Chemistry, Volume , Translated by Pudjaatmaka A.., Erlangga Publisher, Jakarta. arimurti, S., Rahmah, A. U., Omar, A. A., Murugesan, T., . Application of Response Surface Method in the Degradation of Wastewater Containing MDEA Using UV O Advance Oxidation Process, J. Appl. Sci., vol. , pp – riawan, N. S. Dan Astuti, P. . Mengolah Data Statistika dengan Mudah Menggunakan Minitab . Yogyakarta Ministry of ealth of ndonesia . Situasi Penyakit Kanker, Center of Data and nformation, Ministry of ealt of ndonesa, Jakarta. National Cancer nstitute, . Cancer statistics, assessed on th October , https:www.cancer.govabout‐cancerunderstandingstatistics. Nugroho, A., 8 . Synthesis of ‐ ‐Bis ‐ydroxy‐ ‐Metoxybenzilidine cyclopentanone on the vary of temperature at mixing step Sintesa 2‐5‐Bis4‘‐Hidroksi‐3‘‐Metoksibenzilidin Siklopentanon dengan variasi suhu 28 o C, 38 o C, 48 o C pada Fase Pengadukan , Final year project Skripsi , Faculty of Pharmacy, Gadjah Mada University, Yogyakarta. Sardjiman, . Synthesis of Some New Series of Curcumin Analogues, Anti‐oxidative, Anti‐ inflammatory, Antibacterial Activities and Quantitative‐Structure Activity Relationship. Dissertation. Gadjah Mada University. Yogyakarta. Suryohudoyo P., . Basic Carsinogenesis Molecular Dasar Molekuler Karsinogenesis , in the : Capita Selecta Molecular Medicine Kapita Selekta Ilmu Kedokteran Molekuler , nfomedika Publisher , Jakarta. Tonnesen ., Karlsen J., 8 . Studies on Curcumin and Curcuminoids: Alkaline Degradation of. Curcumin. Z. Lebens. Unters Forsch 8 : ‐ . Yuniarti N. . Aktivitas antiinflamasi invivo dan invitro , ‐bis ’‐hidroksi‐ ’‐etoksifenil ‐ , ‐pentadien‐ ‐on ndometasin dan turunannya. Tesis. Yogyakarta: Universitas Gadjah Mada. Joint Scientific Symposium IJJSS 2016 Chiba, 20‐24 November 2016 2 3 EFFERVESCENT TABLET FORMULATION OF PURPLE MANGOSTEEN GARCINIA MANGOSTANA L AND APPLE PYRUS MALUS L PEEL EXTRACTS MT Ghozali a , Rischa Ayuningsih b a Universitas Muhammadiyah Yogyakarta, Yogyakarta 55282, Indonesia b Universitas Muhammadiyah Yogyakarta, Yogyakarta 55183, Indonesia Abstract Purple mangosteen and apple are the two most popular fruits in ndonesia, but very few consume the peel, which is arguably the healthiest part of the whole fruit. Both purple mangosteen and apple peels are rich in antioxidants, which contribute many of their health benefits. People generally use the peels for many purposes, either medical or non‐ medical, by brewing, boiling, and juicing. To make the peels easier to take, the formulation of effervescent tablet is needed. This research aimed to get the optimum effervescent tablet formula of purple mangosteen and apple peel extract, which fulfils the requirement of standard effervescent tablet and physical evaluation. The extraction method in this research is maceration, which used ethanol as the solvent. The process of this effervescent tablet used a wet granulation that optimizes various formulas to get the best one. The analysis of physical effervescent tablet properties used theoretical approach. The result of this study concluded that the best effervescent tablet formula of purple mangosteen and apple peel extract contained citric acid, tartaric acid, sodium bicarbonate with the ratio of : : . Meanwhile, the results of physical evaluation showed that the content uniformity of the effervescent tablets was . gram, the hardness test was . 8 kgcm , the friability test was . , and the solubility test was . minutes. Keywords Purple mangosteen; apple; effervescent; tablet; formulation

1. Introduction

Purple mangosteen Garcinia mangostana L. is a functional plant, since most parts of it can be used for both medicinal and non‐medicinal purposes. The peel of it, which is usually discarded as a waste, has a number of essential health benefits. t is rich in antioxidants, including anthocyanins and xanthones Moongkarndi et al., . Apple Pyrus mallus L is a fruit that is rich in various phytochemical substances; one of them is flavonoids Boyer et al., . Other studies had confirmed that the peel of apple has a higher antioxidant property than its flesh. Simamora, . 2 4 People have traditionally used purple mangosteen peel by steeping and bringing to a boil, while apple peel is by juicing. The proper formulation in processing natural ingredients into a simple preparation easily accepted by society is expected to improve the practicality and interest in using natural medicine. One of the efforts to improve them is to formulate these natural ingredients into effervescent tablets. Some of main advantages of effervescent tablets is that it is easy to prepare and does contain the proper dose. Effervescent tablets also produce a good taste, since their carbonates help improve the taste of certain drugs Lachman et al., . The main purposes of this study were to formulate the peel extracts of purple mangosteen and apple into effervescent tablet and to test their physical properties.

2. Methods

2.1. Materials Materials used in this study came in two types, namely active and additive. Active ingredients were peel extracts of purple mangosteen and apple, while additives included tartaric acid, citric acid, sodium bicarbonate, mannitol, aspartame, PVP, magnesium stearate, and lactose. . . Tools Some tools used in this study included rotary evaporator KA® , some glass tools Pyrex® , some containers for granulation, mortar and stamper, type GTGTB granulate flow tester Erweka® , digital stopwatch, hardness tester Stokes Monsanto® , friability tester TA‐ TA‐ , moisture balance MB Ohaus® , analytical scales AR Ohaus® , oven Memmert drying oven , sieves no. and type AT‐ ndotest Multi Laboratama® , and single punch tablet press Korsch® .

3. Procedures

3.1. Extraction Powdered peels were extracted with a maceration method using ethanol. t was done by immersing the peels into ethanol for days and stirring every day for the perfect results. After days, the extracted peels were filtered and re‐macerated for days to optimize them. The macerated extracts were entirely evaporated using a rotary evaporator to obtain thickened extracts, then weighed with an analytical scale. 3.2. Granule Preparation Preparing effervescent granules of purple mangosteen and apple peel extracts was done by weighing thick extracts mixed with lactose and then preparing mass of wet granules using PVP by sieving the ingredients with sieve no. and then drying them with a temperature of about ‐ °C for hours. After dried, granules were re‐sieved with a sieve no. . The mixture was put into an oven at °C for an hour, so it will be melted. Dried granules obtained were sieved with sieve no. . 3.3. Formulation Effervescent tablets of purple mangosteen and apple peel extracts were made in one formula Formula , but after evaluation of granule, physical, and organoleptic