Penelitian ini masih perlu dikembangkan lebih lanjut. Penelitian yang perlu dilakukan untuk menunjang hasil penelitian ini adalah penelitian mengenai laju penguraian dan umur simpan. Penelitian mengenai laju penguraian akan menunjang hasil pengujian stabilitas fisik yang telah dilakukan pada penelitian ini. Penelitian lain yang perlu dilakukan adalah uji aktivitas dan toksisitas sistem fitosom. Sistem fitosom telah terbukti dapat meningkatkan laju difusi allisin.
Berdasarkan hasil tersebut diharapkan aktivitas ekstrak bawang putih sebagai penurun gula darah dapat ditingkatkan. Hal ini perlu dibuktikan dengan dilakukannya penelitian lanjutan mengenai uji aktivitas fitosom ekstrak bawang putih. Uji toksistas juga perlu dilakukan untuk memastikan keamanan dan mutu sistem fitosom ekstrak bawang putih.
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Penerbit ITB. Bandung. Hal 237-266.
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Amit, P., Tanwar, Y.S., Rakesh, S., & Poojan, P. (2013). Phytosome: Phytolipid Drug Dilivery System for Improving Bioavailability of Herbal Drug. Journal of Pharmaceutical Science and Bioscientific Research (JPSBR).Vol.3(2), 51-57
Annajiah W. (2015).Evaluasi Profil Disolusi Sediaan Lepas Lambat Diltiazem Hidroklorida Yang Beredar Di Pasaran.Skripsi.FKIK Universitas Islam Negri Syarif Hidayatullah. Jakarta. Hlm. 22-23
Ansel.(2008). Pengantar Bentuk Sediaan Farmasi Edisi 4. UI Press. Jakarta.
Halaman 376.
Balamanikandan, T., Balaji, S., & Pandiarajan, J. (2015).Biological Synthesis of Silver Nanoparticles by Using Onion (Allium cepa) Extract and Their Antibacterial and Antifungal Activity.World Applied Sciences Journal. Vol 33 (6):
939-943.
Banerjee, S., K., & Maulik, S., K. (2002). Effect of Garlic on Cardiovasculer Disorders: a Review. Nutrition Journal. Vol. 1 (4), 1-14.
Dash, S., Murthy, P., N., Nath, L., & Chowdhury, P. (2010). Kinetic modeling on drug release from controlled drug delivery systems. Journal Acta Pol Pharm. Vol.
67(3), 217-222.
Departemen Kesehatan Republik Indonesia.(1995). Farmakope Indonesia. Edisi IV. Departemen Kesehatan Republik Indonesia. Jakarta. Halaman 6.
Departemen Kesehatan Republik Indonesia.(2008). Farmakope Herbal Indonesia.Edisi I.Jakarta: Departemen Kesehatan Republik Indonesia.Halaman 6 - 9, 98-103, 110-111, 150 - 163, 171, 174 – 175.
Dewi, A., K., Sumarjaya, I., W., & Srinadi, I., G., A., M. (2013).Penerapan Metode Permukaan Respons dalam Masalah Optimalisasi.E-Jurnal Matematika.Vol2(2), 32-36
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Garg A, Aggarwal D, Garg S dan Sigla AK. 2002. Spreading of Semisolid Formulation, Pharmaceutical technology.
Hernawan, U.. E., & Setyawan, A., D. (2003). Senyawa Oragnosulfur Bawang Putih (Allium sativum L.) dan aktivitas Biologisnya.JournalBiofarmasi.Vol.1(2), 65-76
Hidayat,T., Hidayat, C., Kuntoro, M., D., P., Hastuti, P., & Sumangat, D. (2008).
Optimasi Sintesis Metil Oleat Menggunakan Biokatalis Lipase dari Kecambah BijiJatropa curcas L. Jurnal Pascapanen.Vol. 5 (2),1-9.
Londhe, V., P., Gavasane, A., T., Nipate, S., S., Bandawane, D., D., & Chaudhari, P., D. (2011). Role of Garlic (Allium sativum L) In Various Diseases: An Overview. Journal of Pharmaceutical Research and Opinion.Vol. 1(4),129-134.
Mardiyadi, E., Muttaqien, S. E., Setyawati, D. R., Rosidah, I., and Sriningsih.(2012). Preparasi dan Aplikasi Nanopartikel Kitosan sebagai Sistem Penghantaran Insulin Secara Oral.Prosiding InSINAS MT-25. Halaman 25-30.
Mitkari, B. V., Korde, S. A., Mahadik, K. R., & Kokare, C. R. (2010).
Formulation and evaluation of topical liposomal gel for fluconazole. Dalam:
Indian J Pharm Educ Res. Vol. 44(4), 324-333.
Nazeer, A., A., Veeraiya, S., & Vijaykumar, S., D. (2017). Anti-cancer potency and sustained release of phytosomal diallyl disulfide containing methanolic allium sativum extract against breast cancer.Int. Res.J. Pharm.Vol. 8(8). Halaman 34-40.
Nurmiah, S., Syarief, R., Sukarno, Peranginangin, R., & Nurtama, B. (2013).
Aplikasi Response Surface Methodology pada Optimalisasi Kondisi Proses Pengolahan Alkali Treated Cottonii (ATC). Jurnal Pascapanen dan Bioteknologi Kelautan dan Perikanan. Vol. 8(1),9 – 22.
Octavia, N. (2016). Formulasi Sediaan Gel Hand Sanitizer Minyak Atsiri Pala(Myristica fragransHoutt.) : Uji Stabilitas Fisik Dan Uji AktivitasAntibakteri Terhadap Bakteri Staphylococcus aureu. Journal.Universitas Muhammadyah Surakarta. Surakarta. Hlm. 1-15
Ramadon, d., and Mun’im A. (2016). Pemanfaatan nanoteknologi dalam sistem penghantaran obat baru untuk produk bahan alam. Jurnal ilmu kefarmasian Indonesia. Vol. 14, no. 2. Hlm. 118-127
Rana, M., S., Rohani, S., Hossain, M., N., Rahmatullah, M. (2018). Improved Glucose Tolerance With A Polyherbal Formulation OfColocasia EsculentaTubers AndAllium SativumCloves. World Journal of Pharmaceutical Research (WJPR).Vol 7 (16), 55-61.
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Rowe, Raymond C., Marian E., Queen., Paul J., Sheskey. (2009). Handbook of Pharmaceutical Excipients 6 th Edition. American Pharmacist Assistion and Pharmaceutical Press : Washington DC and London. Halaman 110-113, 385-387, 441-444, 754-755.
Saha, S., Sarma, A., Saikia, P., & Chakrabarty, T. (2013). Phytosome: A Brief Overview. Journal Scholars Academic Journal of Pharmacy (SAJP).Vol 2(1), 12- 20.
Sayuti, N.A. (2015). Formulation and Physical Stability of Cassia alata L. Leaf Extrac Gel. Dalam: Jurnal Kefarmasian Indonesia. Jakarta. Vol.5. Hal 77.
Setiawan, A., S., Yulinah, E., Adnyana, K., Permana, H., & Sudjana, P. (2011).
Efek antidiabetes kombinasi ekstrak bawang putih (Allium sativumLinn) Dan rimpang kunyit (Curcumma domestica Val.) dengan pembanding Glibenklamid pada penderita diabetes mellitus tipe 2.MKB.Vol 43(1).26-34.
Shaikh H. K., Kshirsagar R. V., & Patil S. G. (2015). Mathematical models for drug release characterization: a review. Dalam: World J. Pharm. Pharm. Sci, Vol.
4(4). Mumbai. Hlm. 324-338.
Singla V., Saini S., Joshi B., Rana A.C. (2012). Emulgel : A New Platform For Topical Drug Delivery. Dalam: International Journal of Pharma and Bio Sciences, Vol. 3. 1(01).Punjab. Hlm. 485-498.
Sinko, P., J. (2011). Martin Farmasi Fisika dan Ilmu Farmasetika edisi 5.diterjemahkan oleh Tim Alih Bahasa Sekolah Farmasi ITB. Jakarta : EGC. Hlm 379-383, 498, 513, 514, 537, 538, 114, 145, 151, 154.
Voigt R. (1995). Buku Pelajaran Teknologi Farmasi. Diterjemahkan oleh Soendani N. S. Yogyakarta: UGM Press. Hlm. 116-118, 607-608, 578-583, 609, 613-615.
50 Lampiran 1. Luaran wajib
PHYSICAL STABILITY TEST OF THE OPTIMAL FORMULA PHYTOSOME GARLIC EXTRACT
Rahmah Elfiyani1,2, Naniek Setiadi Radjab1, Anisa Amalia1, Anisa Nurul Wijaya1
1Universitas Muhammadiyah Prof.DR.HAMKA
ABSTRACT
One effort of improve the stability of allicin was to formulate garlic extract into the phytosome delivery system. Components forming and the conditions of making phytosomes affected the physicochemical properties of phytosomes so they need to be optimized to produce phytosomes with optimal physical properties. Phytosomes tend to experience Ostwald ripening during storage due of the relatively small particle size. The purpose of this study was to see the effect of temperature and length of storage time on the physical stability of the optimal formula phytosomes extract of garlic (Allium sativum L). In this study, optimization was carried out on concentration (lecithin and garlic extract), the temperature of manufacture and stirring speed. Optimization is done by using the CCD- RSM (central composite design-response surface methodology) to obtain 30 designs of phytosomes manufacturing. Physical stability tests were
51
carried out at storage temperatures of 40C, 250C, and 400C for 4 weeks.
Evaluations carried out were organoleptic, pH, density, particle size, polydispersity index (PDI), and zeta potential. Optimal design results obtained were the concentrations of garlic extract and lecithin of 4.5%
respectively, the temperature of making 300C and the stirring speed of 125 rpm. The measurement results obtained are a pH value of 5.5-5.73;
density 1.00370-1.00574 g/mL; particle size of 214.3-358.60 nm; PDI 0.458-0.571; and zeta potential of -29.08 to -33.29 mV. Based on the results, it can be concluded that extreme temperatures (40C and 400C) can reduce the physical stability of the phytosome system starting at week 2 to week 4 of storage.
Keywords: garlic extract, allicin, phytosomes, temperature and storage time, physical stability
INTRODUCTION
Methanol extract of garlic at a concentration of 400 mg / kgBB has the effect of reducing blood glucose levels in mice (Akter and Rahmatullah 2018). Garlic extract (Allium sativum L) can be made in the phytosome system by using lecithin as a phospholipid binding agent so that it can increase its stability and absorption (Amit et al. 2013). Previous studies have formulated an ethanol extract of garlic in phytosomes for slow release delivery which is used in the treatment of cancer with satisfactory
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results, i.e that the phytosomes obtained show 100 % toxic to cancer cell lines (MCF 7) at 108.5 μg / ml (Nazeer et al. 2017). Optimal formulas and manufacturing methods are needed to form phytosomes. Optimization of formulas and methods can be done using Response Surface Methodology (RSM) analysis. RSM is a collection of mathematical and statistical techniques that are useful for analyzing problems, where several variables affect a response. Variables that influence on produce the phytosomes are the composition of phosphatidylcholine and garlic extract, as well as temperature conditions and stirring speed. After obtaining the optimum formula and method, physical testing of the phytosomes system is then performed. Physical stability is one of the important factors that will affect the effectiveness of the delivery system and drug preparations. A system or preparation can be said to be physically stable if it can maintain its physical properties during the storage period (Sinko 2011). Physical stability is affected by conditions (temperature and duration) of storage.
Based on this, the research will be tested the effect of temperature and storage duration on the physical stability of the phytosome of garlic extract MATERIAL AND METHODS
Materials
The equipment used in this study include UV-Vis 1601 spectrophotometer (Shimadzu), Analytical Balance (OHAUS), glassware, pH meter (Metler Toledo), Ultracentrifuge (HC1180T type), Vacum Rotary Evaporator (Buchi), Refrigerator, Particle Size Analyzer (Delsa Max), Oven
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(Memmert), and Waterbath (Memmert). The materials used in this study include Allium sativum, 70% Ethanol, lecithin, Aquadest, dichloromethane, potassium dihydrogenphosphate, Sodium hydroxide, and Hydrogen disodium phosphate.
Production of Garlic Extract
Garlic powder weighed 1000 g and extracted with 5000 mL ethanol solvent using maceration method for 48 hours. The results of the crude extract obtained are then filtered using whatman filter paper No. 1 and the solvent was evaporated to form a viscous extract using a Rotary Evaporator at 40 ° C (Akter and Rahmatullah 2018).
Fitosom Optimization Production of phytosome
Phosphatidylcholine is dissolved with dichloromethane, while garlic extract is dissolved with ethanol, then the two mixtures are put into a round bottom flask. Dichloromethane is evaporated using a rotary evaporator at the temperatures listed in Table 1 at the speeds listed in Table 1 and vacuumed until a thin layer is evenly obtained. Then the layer is stored in the refrigerator at a temperature of 2 – 8 oC for up to 24 hours. The thin layer was hydrated with a phosphate buffer solution of pH 5.5 at 40 °C.
After the suspension is formed, do sonication for 2 minutes. Then put it in a glass bottle.
Phytosome evaluation Organoleptic
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The organoleptic examination includes the color, odor, and homogenity of phytosome garlic extract
Density (Departemen Kesehatan Republik Indonesia 2014) Measurement of the value of density is done using a pycnometer.
Entrapment efficiency (Anwar and Farhana 2018)
Done by entering a 0.5 mL sample into a centrifugation tube, then centrifugation is done to separate the active substance that is not entrap in the phytosome at a speed of 14000 rpm for 90 minutes. The supernatant is taken to measure the levels of allicin which are not entrap in the phytosome vesicles. Furthermore, the volume is sufficient by getting 10 mL phosphate buffer pH of 6.8, and the solution is measured using a spectrophotometer. The entrapment efficiency of the allicin is determined using the equation 1:
% 𝐸𝑛𝑡𝑟𝑎𝑝𝑚𝑒𝑛𝑡 𝑒𝑓𝑓𝑖𝑐𝑖𝑒𝑛𝑐𝑦 =
𝑇𝑜𝑡𝑎𝑙 𝑎𝑙𝑙𝑖𝑐𝑖𝑛 𝑖𝑛 𝑠𝑢𝑠𝑝𝑒𝑛𝑠𝑖𝑜𝑛−𝑓𝑟𝑒𝑒 𝑎𝑙𝑙𝑖𝑐𝑖𝑛 𝑐𝑜𝑛𝑐𝑒𝑛𝑡𝑟𝑎𝑡𝑖𝑜𝑛
𝑇𝑜𝑡𝑎𝑙 𝑎𝑙𝑙𝑖𝑠𝑖𝑛 𝑖𝑛 𝑠𝑢𝑠𝑝𝑒𝑛𝑠𝑖𝑜𝑛 𝑥 100%……… (1)
Average of particle size, polydispersity index, and zeta potential (Keerthi et al. 2014)
The sample was diluted with aqua dest (1:9). The instrument will measure the sample for 9 minutes, then the particle size, polydispersion index, and zeta potential of the phytosome vesicles will be measured.
RSM analysis
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Response Surface Methodology (RSM) analysis in this study was used to determine the optimal formula of garlic phytosome (Allium sativum L) with the desired criteria, i.e: particle size 190.4 - 694 nm, polydispersity index 0 - 0.571, zeta potential ± 1.37 - 53.15 mV, entrapment efficiency 37.2354 - 92.7226 % and density 1.
Optimal phytosome evaluation
The evaluation of optimal phytosome is the entrapment efficiency test, density, particle size testing, polydispersity index, zeta potential and pH value using a pH meter at a temperature of 25oC ± 2oC
Phytosome physical stability testing
Physical stability testing is carried out by storing phytosome at 4oC ± 2oC, room temperature (25-30oC ± 20C) and 40oC ± 2oC for 4 weeks and evaluating including organoleptic testing, pH, density, particle size, polydispersity index and zeta potential (Natalia M, 2012).
Data analysis
Data obtained from the physical stability test were then statistically analyzed using the two-way ANOVA analysis test to determine the effect of temperature and storage time on the physical stability of the phytosome of garlic extract.
RESULTS AND DISCUSSION Phytosome Optimization
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The results of an evaluation of the physical and chemical properties of the phytosome system can be seen in Table 1. The results of the evaluation are then analyzed with predetermined criteria to obtain a design plan that meets these criteria. RSM analysis can be seen in Table 2.
RSM analysis results
The variables used in this study are Garlic (A), Lecithin (B), Stirring Speed (C), Temperature (D). while the observed response are entrapment efficiency, density, particle size, zeta potential, and polydispersity index.
Entrapment Efficiency
The equation used is 2FI, where this equation connects responses and variables is as follows:
Y = +62.60 + 1.84*A + 1.43*B - 0.37*C - 0.31*D + 0.68*A*B + 4.50*A*C + 1.08*A*D - 2.88*B*C - 0.97*B*D - 4.18*C*D ………..………. (2)
From the results of the equation obtained showed the Stirring Speed, Temperature, Interaction Between Lecithin and Stirring Speed, Interaction Between Lecithin and Temperature, as well as the interaction between Stirring Speed and Temperature showed a significant effect on the entrapment efficiency.
Density
The equation used is 2FI, where this equation connects responses and variables is as follows:
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Y = +1,02 + 3,237E - 003*A + 1,542E - 004*B - 8,042E - 004*C + 1,679E - 003D - 4,156E - 003*A*B - 1,269E - 003*A*C - 7,437E - 004*A*D + 6,938E - 004*B*C - 1,081E - 003*B*D + 2,331E - 003*C*D ... (3) The results of the equation obtained showed the relationship of stirring speed, interaction between garlic and lecithin, interaction between garlic and stirring speed, interaction of garlic and temperature, as well as interaction of lecithin and temperature showed a significant effect on density.
Particle size
The Linear Equation which connects the response and variables as follows are:
Y = +346.06 + 3,80*A + 59.02*B - 11.18*C + 20.46*D ……… (4) The results of the equation are obtained that the stirring speed shows a significant effect on particle size.
Zetta potential
The linear equation that links the responses and variables is as follows:
Y = +28.71 - 2.81*A - 3.76*B - 1.52*C - 0.36*D ……….… (5) From the results obtained that garlic, lecithin, stirring speed, and temperature showed a significant influence on zetta potential.
Polydispersity index
The 2FI equation that links the responses and variables is as follows:
Y = +0,45 - 0,024*A - 0,056*B + 0,024*C -7,958E - 003*D - 0,036*A*B + 0,083*A*C - 0,036*A*D - 0,036*B*C - 0.012*B*D - 0.036*C*D …………. (6)
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From the equation obtained that lecithin, temperature, interaction of garlic and lecithin, interaction of garlic and temperature, interaction of lecithin and stirring speed, interaction of lecithin and temperature, interaction of stirring speed and temperature showed a significant influence on index polydispersion.
Production and evaluating the optimal phytosome design
Based on the results of RSM analysis, one design was chosen with a concentration of 4.5% garlic and lecithin extract, a temperature of 300C and a stirring speed of 125 rpm. The evaluation results can be seen in Table 2.
Physical stability test Organoleptic
Organoleptic tests include observing the color, odor, and homogeneity of the phytosome of garlic extract. Changes in color and odor do not occur in the phytosome during the storage period. Based on observations at first week, there was no change in homogeneity. Separation of new phases occurred at the time of observation at second week. This separation occurred in the phytosome with storage conditions at 4oC and 40oC.
Phase separation at 4°C according to theory because phosphatidylcholine has a phase transition temperature at temperatures below 10oC or more than 160oC (Rowe 2009). Phase separation at 4oC may be caused because particles tend to stretch at hot temperatures so that the space
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between particles becomes wider, resulting in aggregation and phase separation.
Test of pH
Based on the results obtained, the pH of the phytosome system is 5.5 - 5.73. Changes in pH occur in the phytosome stored at 40oC. Increased pH may be due to positive groups in the binding system of OH groups in the environment. Statistical analysis showed that there were significant differences in pH values at each time and storage temperature.
Density test
The density of the phytosome system is in the range 1.0037 - 1.0057. At storage at a temperature of 40°C, there is a change in the value of density.
This may be due to the termination of bonds in the system causing weight solids to be reduced. Based on statistical analysis, there is a significant difference in the value of density during storage.
Particle size distribution, zeta potential, and polydispersity index Phytosome have nano-sized vesicles with particle sizes of 1-300 nm (Agoes 2010). Based on the measurement results, it can be seen that the particle size of phytosome is 214.3 nm at week 0, so the phytosome is still included in nanoparticle preparations. On observation for 4th weeks, there was an increase in particle size in all storage conditions. This could be due to the potential for the formation of aggregates in nano-sized particles which tended to be larger because the contact angles between particles
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were greater (Sinko 2011). This data was also supported by test results the zeta potential value is also decreasing.
Zeta potential value shows the distance between particles. The greater the potential zeta value, the system can be said to be stable because the possibility of particles forming aggregates is smaller (Mardiyadi et al, 2012). Nanoparticles with zeta potential values approaching ± 30 mV have proven to be stable, the stability of a dosage form is poor if the zeta potential value is smaller than 30 and preparation is said to be stable if the zeta value is greater than 30 (Mardiyadi et al, 2012). From the data obtained, the zeta value is -32.55 mV, meaning that the phytosome preparation with a zeta value greater than 30 mV has good stability. The results of particle size, polydispersity index, and zetta potential can be seen in Table 3.
The particle size distribution is expressed in the polydispersity index value.
Based on the results obtained, the value of the phytosome polydispersity index is 0.458. Polydispersity (PD) refers to the level of particle size homogeneity. The smaller the PD value, the more dispersed the nanoparticle dispersion. According to Anonymous (2013) if the value of % PD is less than 0.15 the particles are considered homogeneous or monodispersed and if the value of % PD is greater than 0 35 particles can be considered unhomogeneous or polydisperse. The results of the phytosome polydispersity index value indicate that the phytosome system is a polydispersion system. Based on the results of statistical analysis,
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there is a significant difference in the particle size, zeta potential, and polydispersion potential in each storage condition.
REFERENCES
Agoes G. 2012. Sistem penghantaran obat pelepasan terkendali. Seri III.
Penerbit ITB. Bandung. pp. 237-266.
Akter F., and Rahmatullah M., 2018. Antihyperglycemic Activity Studies WithMalva Verticillata Leaves. World Journal of Pharmaceutical Research.Vol 7 (19), 107-113
Amit P., Tanwar YS., Rakesh S., and Poojan P., 2013. Phytosome:
Phytolipid Drug Dilivery System for Improving Bioavailability of Herbal Drug. Journal of Pharmaceutical Science and Bioscientific Research (JPSBR).3(2), 51-57
Anwar E., and Farhana N., 2018. Formulation and Evaluation of Phytosome-Loaded Maltodextrin-Gum Arabic Microsphere System for Delivery of Camellia sinensis Extract. Journal of Young Pharmacists.
10(2S), s56-s62
Departemen Kesehatan Republik Indonesia. 2014. Farmakope Indonesia.
Edisi V Jakarta: Direktorat Jendral Pengawasan Obat dan Makanan. pp.
47, 399, 856, 1070, 1553, 1563, 1750.
Keerthi B., Pingali PS., and Srinivas P. 2014. Formulation and evaluation of capsules of ashwagandha phytosomes. Int J Pharm Sci Rev Res.
29(2),.138-142
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Mardiyadi E., Muttaqien SE., Setyawati DR., Rosidah I., and Sriningsih.
2012. Preparasi dan Aplikasi Nanopartikel Kitosan sebagai Sistem Penghantaran Insulin Secara Oral. Prosiding InSINAS MT-25. pp. 25-30.
Natalia M. 2012. Uji Stabilitas Fisik dan Uji Aktivitas Antibakteri Minyak Jintan Hitam (Nigella sativa L.,) yang Diformulasikan sebagai Sistem Nanoemulsi Gel (Nanoemulgel).Skripsi.Universitas Indonesia. Jakarta.
Halaman : 47.
Nazeer, AA., Veeraiya S., and Vijaykumar SD. 2017. Anti-cancer potency and sustained release of phytosomal diallyl disulfide containing methanolic allium sativum extract against breast cancer. Int. Res.J. Pharm.Vol. 8(8).
34-40.
Sinko PJ. 2011. Martin Farmasi Fisika dan Ilmu Farmasetika edisi 5.diterjemahkan oleh Tim Alih Bahasa Sekolah Farmasi ITB. Jakarta : EGC. pp. 379-383, 498, 513, 514, 537, 538, 114, 145, 151, 154.
63
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Table 1. Optimization of phytosome garlic extract (Allium sativum L) based on RSM(Design-Expert 7.1.6)
Run
Factor Response
A: Concentration of garlic extract (%)
B: Concentration of lecithin (%)
C: Temperature (celcius)
D: Stirring speed (rpm)
Entrapment efficiency (%)
Polydispersity index
Zeta Potential (mV)
Particle size (nm)
Density (g/mL)
1 7.5 4.5 40 125 69.494 0.571 18.12 212.9 1.0237
2 6 6 35 100 92.7226 0.571 4.33 190.4 1
3 4.5 7.5 30 75 71.3422 0.571 27.27 219.8 1.0188
4 7.5 4.5 30 75 43.6837 0.571 25.49 260.6 1.0271
5 4.5 7.5 40 125 59.4557 0.19 1.37 694 1.219
6 7.5 7.5 40 75 73.9598 0.19 4.73 624.3 1.0139
7 7.5 7.5 30 125 80.1088 0.571 3.51 434.9 1.0142
8 6 6 35 100 66.9369 0.571 15.88 303.3 1.013
9 4.5 4.5 30 125 64.4466 0.571 27.88 330.2 1.0034
10 4.5 4.5 40 75 64.3559 0.571 16.6 373.7 1.0081
11 4.5 4.5 30 75 69.3217 0 13.42 384.2 1.0133
12 7.5 4.5 30 125 75.2103 0.571 32.09 340.2 1.0233
13 7.5 7.5 30 75 66.2674 0 20.65 501.6 1.0258
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14 7.5 4.5 40 75 63.5148 0.571 37.21 293.6 1.0322
15 7.5 7.5 40 125 53.3698 0.571 17.48 219.2 1.0228
16 4.5 4.5 40 125 49.4948 0.571 23.14 279.7 1.0199
17 6 6 35 100 50.4389 0.571 47.37 259.6 1.0229
18 6 6 35 100 37.2354 0.571 44.26 221.3 1.0109
19 4.5 7.5 30 125 59.0405 0 19.44 440.3 1.0206
20 4.5 7.5 40 75 68.688 0.571 36.1 424.7 1.0203
21 6 6 35 50 65.9282 0.571 39.21 328.8 1.0244
22 9 6 35 100 56.3523 0 20.8 386.2 1.0259
23 6 6 35 100 41.9372 0.571 47.68 449.1 1.0197
24 3 6 35 100 43.9952 0.571 51.5 211 1.0154
25 6 3 35 100 63.8584 0.571 53.15 223 1.0205
26 6 6 45 100 71.5393 0 45.04 433.4 1.0242
27 6 6 35 100 62.1885 0.571 45.79 399.3 1.0249
28 6 9 35 100 64.6292 0.571 39.77 389.4 1.0187
29 6 6 35 150 66.79 0.571 40.19 260.2 1.0196
30 6 6 25 100 61.7163 0.571 41.82 293 1.0122
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Table2. Results of optimal phytosome formula evaluation
No Subject Results
1. Organoleptic - Color - Shape - Odor - Taste
Brown Liquid Typical garlic
Bitter
2. Density 1.0051 g/mL
3. Zeta potential -32.55 mV
4. Polidispersity index 0.571
5. Particle size 270 nm
6. Entrapment efficiency 64.8798 %
Table3. Result of particle size, zeta potential, polidispersity index of phytosome garlic extract
Temperature Evaluation
Week of observation
0 1 2 4
40C Particle size (nm)* 214.3 1.32 217.86 0.51 242.8 15.88 307.36 10.55 Zeta potential (mV)* -29.08 0.85 -28.52 0.79 -28.45 2.61 -33.82 12.31 Polidispersity index (%)* 0.46 0.12 0.45 0.04 0.56 0.02 0.57 0.0 250C Particle size (nm)* 214.3 1.32 219.16 0.65 286.9 3.27 321.36 1.62
Zeta potential (mV)* -29.08 0.85 -27.98 0.99 -27.49 2.75 -34.96 11.15 Polidispersity index (%)* 0.46 0.12 0.46 0.10 0.57 0.0 0.57 0.0 400C Particle size (nm)* 214.3 1.32 227.33 3.57 292.8 2.07 358.6 45.5
Zeta potential (mV)* -29.08 0.85 -29.45 1.75 -24.84 4.08 -33.29 8.45
67
Polidispersity index (%)* 0.46 0.12 0.46 0.08 0.57 0.0 0.57 0.0
*n=3
Figure 1. RSM analysis results
B: Lecithin
A: Garlic extract
68 Lampiran 2. Luaran tambahan
Peningkatan Laju Difusi Allisin dalam Sistem Fitosom Ekstrak Bawang Putih Enhancement Allicin Diffusion Rate in The Garlic Extract Phytosome System
Anisa Amalia1,2, Rahmah Elfiyani1, Adesi Chenia1
1Universitas Muhammadiyah Prof. DR. Hamka
ABSTRAK
Bawang putih (Allium sativum L) diketahui mengandung allisin yang memiliki khasiat sebagai penurun gula darah. Penelitian sebelumnya menunjukkan ekstrak metanol bawang putih 400 mg/kgBB dapat menurunkan kadar gula darah pada mencit. Penetrasi allisin dapat ditingkatkan dengan memformulasikan ekstrak kedalam bentuk sistem penghantaran fitosom. Pada penelitian ini akan dilihat pengaruh pembuatan sistem fitosom ekstrak bawang putih terhadap laju difusi allisin. Fitosom ekstrak bawang putih dibuat menggunakan metode hidrasi lapis tipis. Evaluasi yang dilakukan adalah pengujian sifat fisikokimia yang meliputi uji efisiensi penjerapan, berat jenis, ukuran partikel, indeks polidispersi dan potensial zeta. Penentuan laju difusi allisin pada ekstrak dan sistem fitosom dilakukan menggunakan sel difusi termodifikasi selama 420 menit. Hasil evaluasi menunjukkan fitosom memiliki nilai efisiensi penjerapan 64,8789% denagn berat jenis 1,0051, ukuran partikel 270 nm, potensial zeta -32,55mV dan indeks polidispersi 0,571. Hasil pengujian laju difusi menunjukkan sistem fitosom dapat mempercepat laju difusi allisin bila dibandingkan dengan laju difusi allisin dalam ekstrak bawang putih.
Kata kunci: allisin, ekstrak bawang putih, fitosom, laju difusi
ABSTRACT
Garlic (Allium sativum L) contains allicin which has the property of reducing blood sugar levels. In previous studies, methanol extract of garlic can reduce blood sugar levels in mice at a dose of 400 mg/kgBW. The penetration of allicin can be increased by formulating extracts in the phytosome system.
In this study, it will be observed the effect of making a phytosome system on the diffusion rate of allicin.
Garlic extract phytosome was made using a thin layer hydration method which was then evaluated for its physicochemical properties which included testing of entrapment efficiency, density, particle size, index polydispersion and the zeta potential. Determination of the value of the diffusion rate of allisin in the extract and in the phytosome system was carried out using a modified diffusion cell for 420 minutes. The phytosome system formed has an entrapment efficiency value of 64.8789% with a density of 1.0051 g/mL, particle size of 270 nm, zeta potential of -32.55 mV and the polydispersion index of 0.571.
Diffusion rate testing indicate the diffusion rate of the phytosome system can increase the diffusion rate of allicin when compared to the diffusion rate of allisin in garlic extract.
Keyword : allicin, garlic extract, phytosome, diffusion rate.