{"id":62067,"date":"2024-12-30T11:22:31","date_gmt":"2024-12-30T11:22:31","guid":{"rendered":"https:\/\/biomedpharmajournal.org\/?p=62067"},"modified":"2025-01-06T18:25:49","modified_gmt":"2025-01-06T18:25:49","slug":"evaluation-of-self-nanoemulsifying-drug-delivery-system-from-qusthul-hindi-saussurea-lappa-extract-in-vitro-release-and-absorption-assessment","status":"publish","type":"post","link":"https:\/\/biomedpharmajournal.org\/staging\/vol17no4\/evaluation-of-self-nanoemulsifying-drug-delivery-system-from-qusthul-hindi-saussurea-lappa-extract-in-vitro-release-and-absorption-assessment\/","title":{"rendered":"Evaluation of Self Nanoemulsifying Drug Delivery System from Qusthul Hindi (Saussurea lappa) Extract: In vitro Release and Absorption Assessment"},"content":{"rendered":"\n

Introduction<\/strong><\/p>\n\n\n\n

Pharmaceutical formulation technology and drug delivery systems are essential in discovering new pharmaceutical therapies1<\/sup> . Developing a drug delivery system generally takes a long time because many variables must be optimized to obtain a formula that meets predetermined specifications. A drug delivery system can be used to develop chemotherapy drugs or cancer treatments that kill abnormal cells in the body, so it is necessary to develop technology to reduce side effects 2<\/sup> .<\/p>\n\n\n\n

Applying drug delivery systems to natural products has several advantages, including increasing solubility, increasing bioavailability, reducing toxicity, increasing pharmacological activity, increasing stability, and preventing physical or chemical degradation3<\/sup>. Preparations based on drug delivery systems can be an alternative to pharmaceutical preparations that contain natural ingredients.<\/p>\n\n\n\n

Based on data on the solubility and pharmacological activity of Qustul Hindi extract, it is necessary to develop formulation technology to increase its solubility, stability, and bioavailability to maximize the therapeutic effect by using the extract as a medicinal compound. One technology widely used in formulation is nanoparticle technology, which has now become a model for developing drug delivery systems4<\/sup>. Research on the ability of SNEDDS to increase the bioavailability of drugs with low solubility in systemic circulation has been widely proven compared to conventional preparations such as tablets.<\/p>\n\n\n\n

Using nanotechnology, bioactive components from herbal ingredients can be isolated and encapsulated into nanoparticles to increase drug availability and facilitate drug delivery to the target location. Therefore, in this research, researchers will develop a standardized formulation and downstream nanotechnology preparation of qusthul Hindi as a chemopreventive agent to minimize the side effects of chemotherapy 4<\/sup>.<\/p>\n\n\n\n

Qusthul Hindi, indigenous to the Himalayan region, has gained attention due to its various metabolites, including sesquiterpenes, flavonoids, phytosterols, lignans, and terpenes, which have pharmacological effects as chemotherapy agents. To further validate these components and subsystems, metabolite profiling will be conducted to determine significant compounds in the extract responsible for its pharmacological activity, specifically as chemopreventive. Therefore, this study aimed to determine the release and absorption flux values of qusthul Hindi SNEDDS using the template formula for the optimal D-optimal design approach.<\/p>\n\n\n\n

Materials and Methods<\/strong><\/p>\n\n\n\n

Materials<\/strong><\/p>\n\n\n\n

The main ingredient used in this study was the qusthul Hindi extract obtained from Saudi Arabia as costus root powder. The simplicity was identified in the pharmaceutical biology laboratory, Faculty of Medicine and Health Sciences, UIN Maulana Malik Ibrahim Malang, using macroscopic and microscopic approaches to ensure the accuracy of the name. The specimen was labeled with the number 075\/212\/102 20-A\/2022. <\/p>\n\n\n\n

Ingredient formulation comprised Miglyol 812 (Sigma Aldrich, USA), Tween 80 and PEG 400 (Merck, Germany), Ethanol 96% (Smartlab, Indonesia), HCl, NaOH, KH2<\/sub>PO4<\/sub>, HCl, NaCl, MgCl2<\/sub>, CaCl2<\/sub>, NaHCO3<\/sub>, KCl, NaHPO4 <\/sub>pro analysis (Merck, Germany).<\/p>\n\n\n\n

Research Design <\/strong><\/p>\n\n\n\n

This study used an experimental\nlaboratory design focused on SNEDDS formulations using different active\ningredients. The optimal formula template from a previous investigation was\nachieved with the optimal D-design approach using Design-Expert\u00ae<\/sup>12\nsoftware5<\/sup> . This study used further formula application\nwith a different active ingredient, qusthul Hindi. The effectiveness\nexaminations carried out were release and absorption tests. The release test used\nthe dialysis bag method, while the absorption test used the reverse gut\ntechnique.<\/p>\n\n\n\n

Method<\/strong><\/strong><\/p>\n\n\n\n

Preparation of Qusthul\nHindi (Saussurea lappa<\/em>) Extract<\/strong><\/strong><\/p>\n\n\n\n

Extraction\nwas carried out using the maceration method with the help of\nultrasound-assisted extraction. Qustul Hindi was extracted thrice using 500 mL\nof 96% ethanol at room temperature at 10-minute intervals. Approximately 25\ngrams of sample was dissolved in 500 mL of 96% ethanol at a ratio of 1:20.\nAfter obtaining the liquid extract, it was concentrated using a rotary\nevaporator (Heidolph, Germany). After obtaining a thick extract, an\nethanol-free examination is carried out to ensure no solvent influence in the\nextract. This examination is carried out by adding H2<\/sub>SO4<\/sub>\n(p) to the extract, then adding CH3COOH, then heating. The test result is\nnegative if there is no characteristic ester odor.<\/strong><\/p>\n\n\n\n

Formulation of SNEDDS\nQusthul Hindi (Saussurea lappa<\/em>)\nExtract<\/strong><\/strong><\/p>\n\n\n\n

The SNEDDS\nformula was prepared using the D-optimal design approach based on a previous\ntemplate6<\/sup>. The components included 50 mg of qusthul Hindi\nextract, 2.13%, Miglyol 812 (oil component), 5.81% Tween 80 (surfactant), and\n2.06% PEG 400 (co-surfactant)7\u20139<\/sup>.<\/strong><\/p>\n\n\n\n

Preparation for Making Release and\nAbsorption Test Media<\/strong><\/strong><\/p>\n\n\n\n

The\nmedia used in this study were artificial gastric fluid (AGF) at pH 1.2 \u00b1 0.05\nand artificial intestinal fluid (AIF) at pH 6.8 \u00b1 0.05. As illustrated in Table\n1, the media were prepared by dissolving each ingredient with distilled water,\nand then the degree of acidity of the solution was measured with a pH meter10<\/sup>.<\/p>\n\n\n\n

Table 1: Composition of artificial gastric fluid pH 1.2 \u00b1 0.05 and artificial intestinal fluid pH 6.8 \u00b1 0.05<\/strong><\/p>\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n
\n

Materials<\/strong><\/p>\n<\/td>\n

\n

Weight(gram)<\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

Artificial Gastric Fluid (AGF)<\/p>\n<\/td>\n<\/tr>\n

\n

NaCl<\/p>\n<\/td>\n

\n

2<\/p>\n<\/td>\n<\/tr>\n

\n

HCl<\/p>\n<\/td>\n

\n

7<\/p>\n<\/td>\n<\/tr>\n

\n

CO2<\/sub>-free distilled water<\/p>\n<\/td>\n

\n

ad1L<\/p>\n<\/td>\n<\/tr>\n

\n

Artificial Intestinal Fluid (AIF)<\/p>\n<\/td>\n<\/tr>\n

\n

MgCl2<\/p>\n<\/td>\n

\n

0.152<\/p>\n<\/td>\n<\/tr>\n

\n

CaCl2<\/p>\n<\/td>\n

\n

0.147<\/p>\n<\/td>\n<\/tr>\n

\n

KCl<\/p>\n<\/td>\n

\n

0.093<\/p>\n<\/td>\n<\/tr>\n

\n

NaCl<\/p>\n<\/td>\n

\n

1.758<\/p>\n<\/td>\n<\/tr>\n

\n

NaHCO3<\/p>\n<\/td>\n

\n

0.420<\/p>\n<\/td>\n<\/tr>\n

\n

CO2<\/sub>-free distilled water<\/p>\n<\/td>\n

\n

ad 500 mL<\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

 <\/p>\n\n\n

Preparation of Release and Absorption\nTest Membrane<\/strong><\/strong><\/p>\n\n\n\n

The\nrelease membrane used in the test was a 12,000 g\/mole dialysis bag with a 0.45\n\u03bcg filter. The preparation method is to cut the membrane 5 cm long and then\nsoaked in distilled water for (\u00b112 hours). Immediately before use, the membrane\nis drained until no water sticks to it. A dialysis bag ready to be filled with\n1 gram of sample is then tied at the bottom and top ends using thread. Before\nusing the dialysis bag, ensure that the dialysis bag filled with the sample\ndoes not leak.<\/p>\n\n\n\n

The\nabsorption test membrane was used in rat intestines. Experimental animals were\nfasted for 20 – 24 hours but were given boiled water. The mice were euthanized\nusing ether under anesthesia for 20 minutes, then their stomachs were opened\nalong the linea mediana, and the intestines were removed. The intestine was\nremoved 15 cm below the pylorus, and 20 cm below it was cut for experiments.\nThe intestine is divided into two equal parts and then cleaned. The anal\nsection was used as a control. The anal end of the piece of the intestine is\ntied with thread; then, using a glass rod with a diameter of 2 mm, the\nintestine is inverted so that the mucosa is located outside.<\/strong><\/p>\n\n\n\n

The Release Test of Qusthul Hindi\n(Saussurea lappa<\/em>) Extract<\/strong><\/strong><\/p>\n\n\n\n

The\nrelease test used a type 2 paddle type dissolution equipment8<\/sup>, and the media used was 500 mL with a\ntemperature of 37oC \u00b1 0.5oC. The dialysis bag containing the sample was\ninserted into a chamber containing 500 mL of artificial gastric fluid (AGF) at\npH 1.2 \u00b1 0.05, and the device was run. The release media used were AGF, at pH\n1.2 \u00b1 0.05, and artificial intestinal fluid (AIF), at pH 6.8 \u00b1 0.05. Stirring\nwas carried out at a speed of 100 rpm to maintain the homogeneity of the\nrelease medium. The distance of the paddle base from the bottom of the chamber\nwas 2.5 \u00b1 0.2 cm, and the release test was carried out for 4 hours. Sampling\nwas conducted at 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140,\n150, 160, 170, 180, 190, 200, 210, 220, 230, and 240 minutes with the number of\nsamples per collection being 3 ml. The release media was added at each sampling\nwith a 3 mL AGF solution volume. The samples taken were then filtered, and the\nabsorbance of the filtrate was measured using a spectrophotometer (Shimadzu\nUV-1800) at the maximum wavelength. In addition, the release test was carried\nout in three replications, while the absorbance results were used to calculate\nthe cumulative amount at a specific time interval. The levels\nwere calculated using the standard curve equation, and a release profile was\ncreated by entering the levels released at a particular time. The steps were\nrepeated in AIF pH 6.8 \u00b1 0.059<\/sup> for the release test.<\/strong><\/p>\n\n\n\n

In vitro study for Absorption\nTesting of SNEDDS Qusthul Hindi (Saussurea\nlappa<\/em>) <\/strong><\/strong><\/p>\n\n\n\n

Absorption\ntesting was carried out using Crane and Wilson tubes. The cannula is inserted\ninto the oral end of the unattached intestine. The intestine was measured with\nan effective length of 7 cm, which was previously filled with 1.4 mL serosal\nfluid consisting of 0.9% w\/v NaCl solution. The intestinal bag filled with\nserosal fluid is put into a tube filled with 75 mL of artificial gastric fluid\n(AGF) pH 1.2 \u00b1 0.05 (which contains SNEDDS extract of qustul Hindi at a\ntemperature of 37\u00b0C. Intestinal control bags were carried out the same way but\nusing SNEDDS without Qustul Hindi extract. During the experiment, all parts of\nthe intestine were submerged in mucosal fluid and continuously supplied with\noxygen gas at approximately 100 bubbles per minute. The drug level in the\nserosal fluid is determined at a particular time. For this determination, 1 mL\nof serosal fluid is taken through a cannula and filled with 1 mL of 0.9% w\/v\nNaCl solution. The absorption test is carried out for 4 hours. Samples are\ntaken in minutes 10, 20, 30, 40, 50, 60,70, 80, 90, 100, 110, 120, 130, 140,\n150, 160, 170, 180, 190, 200, 210, 220, 230, and 240. The absorption test was\ncarried out three times. The absorbance results were used to calculate the\ncumulative amount at a specific time interval. The levels are calculated using\nthe standard curve equation, and a release profile is created by entering the\nlevels released at a particular time. The same steps were repeated for\nabsorption testing using artificial intestinal fluid (AIF) medium pH 6.8 \u00b1 0.05\n9<\/sup>.<\/strong><\/p>\n\n\n\n

Data Analysis<\/strong><\/strong><\/p>\n\n\n\n

Determination of the cumulative\namount released\/absorbed from SNEDDS per unit membrane area at any time was\ncalculated from the levels obtained at each time (\u03bcg\/mL) correlated using the\nWurster formula multiplied by the amount of media and divided by the membrane\nsurface area. Subsequently, a curve was created between the cumulative amount\nreleased\/absorbed (\u03bcg\/cm2) versus time. A regression equation was obtained\nbased on the resulting curve: y = bx + a. According to Fick’s law of diffusion,\nthe slope of the regression equation is the speed of release and absorption. <\/p>\n\n\n\n

The Wurster formula equation is as follows: <\/p>\n\n\n\n

Cn     = C\u2019n + \ud835\udc49\ud835\udc60<\/sup>\u2211N\u22121 <\/sup>\ud835\udc36\ud835\udc60\ud835\udc49\ud835\udc5a<\/sub>s\u22121 <\/p>\n\n\n\n

Cn     = Actual levels after correction (ppm)<\/p>\n\n\n\n

C\u2019n    = Readable levels (calculation results from\nthe sample absorption values read on the<\/p>\n\n\n\n

   spectrophotometer in ppm<\/p>\n\n\n\n

Cs      = Readability from previous samples <\/p>\n\n\n\n

Vs      = Sample volume taken<\/p>\n\n\n\n

Vm     = Media\nvolume<\/p>\n\n\n\n

Results and Discussion<\/strong><\/p>\n\n\n\n

The Release Test of SNEDDS Qusthul\nHindi (Saussurea lappa<\/em>)<\/strong><\/strong><\/p>\n\n\n\n

Results of determining the average cumulative amount of qustul Hindi extract released in SNEDDS qustul Hindi extract and qustul Hindi extract solution on AGF media 1.2 \u00b1 0.05 and AIF 6.8 \u00b1 0.2 can be seen in Table 2. The results of the cumulative amount released are then used to create a curve relating the cumulative amount of drug released to time (minutes). The release test was replicated three times for SNEDDS of qustul Hindi extract and qustul Hindi extract solution, which was carried out for 4 hours. The initial concentration of the extract used in the test was 5000.045 \u03bcg and 5004.133 \u03bcg for the SNEDDS extract of qustul Hindi. The released qustul Hindi extract was calculated to obtain a cumulative amount over 4 hours. Figure 1 shows the release profile of qustul Hindi extract and qustul Hindi extract solution on AGF 1.2 \u00b1 0.05 and AIF 6.8 \u00b1 0.2 media. Based on the release profile and continued calculation of the release flux, SNEDDS of qustul Hindi extract provides a higher release of 3.82 times than qustul Hindi extract solution on AGF 1.2 \u00b1 0.05 and AIF media. 6.8 \u00b1 0.2.<\/p>\n\n\n\n\n\n
\"\"<\/td>\n\n

Figure 1: Graph of the cumulative amount of qusthul Hindi extract (\u03bcg\/cm2<\/sup>) released<\/strong><\/p>\n

\u00a0<\/p>\n

\u00a0<\/p>\n

Click here to view Figure<\/a><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

\u00a0<\/p>\n\n\n

Table 2: The cumulative amount of qustul Hindi extract (\u03bcg\/cm2<\/sup>) released (p-value 0.05)<\/strong><\/p>\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n
\n

Time (minute)<\/strong><\/p>\n<\/td>\n

\n

Cumulative amount of SNEDDS extracts<\/strong><\/p>\n

qusthul Hindi shedding (\u03bcg\/cm2<\/sup>)*<\/strong><\/p>\n<\/td>\n

\n

Cumulative amount of extract solution<\/strong><\/p>\n

qusthul Hindi shedding (\u03bcg\/cm2<\/sup>)*<\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

AGF 1.2 \u00b1 0.05<\/strong><\/p>\n<\/td>\n

\n

AIF 6.8 \u00b1 0.2<\/strong><\/p>\n<\/td>\n

\n

AGF 1.2 \u00b1 0.05<\/strong><\/p>\n<\/td>\n

\n

AIF 6.8 \u00b1 0.2<\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

10<\/p>\n<\/td>\n

\n

31.081 \u00b1 1.008<\/p>\n<\/td>\n

\n

27.991 \u00b1 0.054<\/p>\n<\/td>\n

\n

2.874 \u00b1 0,289<\/p>\n<\/td>\n

\n

1.511 \u00b1 0.166<\/p>\n<\/td>\n<\/tr>\n

\n

20<\/p>\n<\/td>\n

\n

32.049 \u00b1 1.949<\/p>\n<\/td>\n

\n

28.191 \u00b1 0.150<\/p>\n<\/td>\n

\n

2.898 \u00b1 0,381<\/p>\n<\/td>\n

\n

1.469 \u00b1 0.078<\/p>\n<\/td>\n<\/tr>\n

\n

30<\/p>\n<\/td>\n

\n

33.503 \u00b1 0.607<\/p>\n<\/td>\n

\n

29.491 \u00b1 0.041<\/p>\n<\/td>\n

\n

2.930 \u00b1 0,302<\/p>\n<\/td>\n

\n

1.667 \u00b1 0.156<\/p>\n<\/td>\n<\/tr>\n

\n

40<\/p>\n<\/td>\n

\n

34.646 \u00b1 0.970<\/p>\n<\/td>\n

\n

30.911 \u00b1 0.015<\/p>\n<\/td>\n

\n

3.045 \u00b1 0,545<\/p>\n<\/td>\n

\n

1.817 \u00b1 0.076<\/p>\n<\/td>\n<\/tr>\n

\n

50<\/p>\n<\/td>\n

\n

35.303 \u00b1 1.284<\/p>\n<\/td>\n

\n

31.291 \u00b1 0.025<\/p>\n<\/td>\n

\n

3.408 \u00b1 0,569<\/p>\n<\/td>\n

\n

2.544 \u00b1 0.179<\/p>\n<\/td>\n<\/tr>\n

\n

60<\/p>\n<\/td>\n

\n

36.959 \u00b1 0.140<\/p>\n<\/td>\n

\n

31.901 \u00b1 0.015<\/p>\n<\/td>\n

\n

3.611 \u00b1 0,733<\/p>\n<\/td>\n

\n

4.955 \u00b1 0.722<\/p>\n<\/td>\n<\/tr>\n

\n

70<\/p>\n<\/td>\n

\n

38.138 \u00b1 0.727<\/p>\n<\/td>\n

\n

32.910 \u00b1 0.015<\/p>\n<\/td>\n

\n

3.897 \u00b1 0,423<\/p>\n<\/td>\n

\n

7.568 \u00b1 0.117<\/p>\n<\/td>\n<\/tr>\n

\n

80<\/p>\n<\/td>\n

\n

39.492 \u00b1 1.871<\/p>\n<\/td>\n

\n

33.091 \u00b1 0.021<\/p>\n<\/td>\n

\n

4.522 \u00b1 1,262<\/p>\n<\/td>\n

\n

9.087 \u00b1 0.407<\/p>\n<\/td>\n<\/tr>\n

\n

90<\/p>\n<\/td>\n

\n

39.110 \u00b1 1.259<\/p>\n<\/td>\n

\n

33.941 \u00b1 0.015<\/p>\n<\/td>\n

\n

4.900 \u00b1 1,170<\/p>\n<\/td>\n

\n

9.267 \u00b1 0.511<\/p>\n<\/td>\n<\/tr>\n

\n

100<\/p>\n<\/td>\n

\n

31.081 \u00b1 1.008<\/p>\n<\/td>\n

\n

34.291 \u00b1 0.251<\/p>\n<\/td>\n

\n

5.018 \u00b1 1,030<\/p>\n<\/td>\n

\n

10.840 \u00b1 0.239<\/p>\n<\/td>\n<\/tr>\n

\n

110<\/p>\n<\/td>\n

\n

32.049 \u00b1 1.949<\/p>\n<\/td>\n

\n

35.911 \u00b1 0.235<\/p>\n<\/td>\n

\n

5.339 \u00b1 1,498<\/p>\n<\/td>\n

\n

11.650 \u00b1 1.117<\/p>\n<\/td>\n<\/tr>\n

\n

120<\/p>\n<\/td>\n

\n

33.503 \u00b1 0.607<\/p>\n<\/td>\n

\n

36.111 \u00b1 0.148<\/p>\n<\/td>\n

\n

5.557 \u00b1 1,652<\/p>\n<\/td>\n

\n

12.942 \u00b1 0.686<\/p>\n<\/td>\n<\/tr>\n

\n

130<\/p>\n<\/td>\n

\n

34.646 \u00b1 0.970<\/p>\n<\/td>\n

\n

47.141 \u00b1 0.214<\/p>\n<\/td>\n

\n

6.610 \u00b1 0,195<\/p>\n<\/td>\n

\n

14.240 \u00b1 0.663<\/p>\n<\/td>\n<\/tr>\n

\n

140<\/p>\n<\/td>\n

\n

38.691 \u00b1 5.120<\/p>\n<\/td>\n

\n

48.951 \u00b1 0.154<\/p>\n<\/td>\n

\n

6.592 \u00b1 0,121<\/p>\n<\/td>\n

\n

16.071 \u00b1 0.352<\/p>\n<\/td>\n<\/tr>\n

\n

150<\/p>\n<\/td>\n

\n

45.438 \u00b1 1.064<\/p>\n<\/td>\n

\n

49.991 \u00b1 0.457<\/p>\n<\/td>\n

\n

6.741 \u00b1 0,737<\/p>\n<\/td>\n

\n

16.901 \u00b1 0.385<\/p>\n<\/td>\n<\/tr>\n

\n

160<\/p>\n<\/td>\n

\n

47.513 \u00b1 3.151<\/p>\n<\/td>\n

\n

50.191 \u00b1 0.450<\/p>\n<\/td>\n

\n

9.558 \u00b1 2,443<\/p>\n<\/td>\n

\n

16.919 \u00b1 1.077<\/p>\n<\/td>\n<\/tr>\n

\n

170<\/p>\n<\/td>\n

\n

48.439 \u00b1 3.638<\/p>\n<\/td>\n

\n

55.221 \u00b1 0.542<\/p>\n<\/td>\n

\n

10.235 \u00b1 0,912<\/p>\n<\/td>\n

\n

17.322 \u00b1 0.755<\/p>\n<\/td>\n<\/tr>\n

\n

180<\/p>\n<\/td>\n

\n

49.287 \u00b1 4.094<\/p>\n<\/td>\n

\n

56.991 \u00b1 0.012<\/p>\n<\/td>\n

\n

9.918 \u00b1 0,792<\/p>\n<\/td>\n

\n

18.011 \u00b1 0.306<\/p>\n<\/td>\n<\/tr>\n

\n

190<\/p>\n<\/td>\n

\n

50.639 \u00b1 1.581<\/p>\n<\/td>\n

\n

57.351 \u00b1 0.002<\/p>\n<\/td>\n

\n

10.266 \u00b1 0,768<\/p>\n<\/td>\n

\n

18.512 \u00b1 1.212<\/p>\n<\/td>\n<\/tr>\n

\n

200<\/p>\n<\/td>\n

\n

50.999 \u00b1 1.314<\/p>\n<\/td>\n

\n

58.491 \u00b1 0.050<\/p>\n<\/td>\n

\n

10.110 \u00b1 1,887<\/p>\n<\/td>\n

\n

18.728 \u00b1 0.582<\/p>\n<\/td>\n<\/tr>\n

\n

210<\/p>\n<\/td>\n

\n

51.607 \u00b1 1.331<\/p>\n<\/td>\n

\n

59.491 \u00b1 0.208<\/p>\n<\/td>\n

\n

11.121 \u00b1 0,092<\/p>\n<\/td>\n

\n

19.519 \u00b1 0.859<\/p>\n<\/td>\n<\/tr>\n

\n

220<\/p>\n<\/td>\n

\n

52.297 \u00b1 1.483<\/p>\n<\/td>\n

\n

60.991 \u00b1 0.158<\/p>\n<\/td>\n

\n

12.811 \u00b1 4,084<\/p>\n<\/td>\n

\n

20.026 \u00b1 0.687<\/p>\n<\/td>\n<\/tr>\n

\n

230<\/p>\n<\/td>\n

\n

54.157 \u00b1 2.057<\/p>\n<\/td>\n

\n

65.021 \u00b1 0.152<\/p>\n<\/td>\n

\n

13.516 \u00b1 0,629<\/p>\n<\/td>\n

\n

20.630 \u00b1 1.412<\/p>\n<\/td>\n<\/tr>\n

\n

240<\/p>\n<\/td>\n

\n

55.950 \u00b1 2.196<\/p>\n<\/td>\n

\n

67.191 \u00b1 0.068<\/p>\n<\/td>\n

\n

13.897 \u00b1 1,715<\/p>\n<\/td>\n

\n

20.228 \u00b1 0.729<\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

*Data are expressed as mean\u00b1SD, n=3<\/p>\n\n\n

The release movement that occurred in the test was observed for 240 minutes. Based on curve one, there was an increase in the cumulative amount released on a flat curve. This indicates a difference in the cumulative amount of drug content released in the AGF medium pH 1.2 \u00b1 0.05 and AIF pH 6.8 \u00b1 0.05. It can be concluded that the results of the SNEDDS extract of qustul Hindi on AIF media provide a higher release than on AGF media. This is possible because the number of hydronium ions in the pH 1.2 \u00b1 0.05 medium could not significantly release the qustul Hindi extract in SNEDDS. The increase in the cumulative amount of drug content released in media pH 6.8 \u00b1 0.05 is due to the solubility of SNEDDS extract of qustul Hindi used in this study, namely 7.04 – 7.33, causing a tendency for more neutral solubility at pH 6, 8 \u00b1 0.05. The release profile in AGF media pH 1.2 \u00b1 0.05 and AIF pH 6.8 \u00b1 0.05 occurred following the first-order reaction. The conclusion that can be drawn at the initial contact of SNEDDS with the media is that the release is influenced by the ability of the media solution to dissolve SNEDDS. The better the ability, the greater the drug that can be released. From the release data in Table 1, a linear regression equation was created between the cumulative amount (\u03bcg\/cm2<\/sup>) and the time (minutes) released. The discharge flux value is the slope of the linear regression equation. The SNEDDS release flux values of qustul Hindi extract. The qustul Hindi extract solution can be seen in Table 3.<\/p>\n\n\n\n

Table 3: The release flux (\u00b5g\/cm2<\/sup>\/minute) of SNEDDS and qusthul Hindi extract solution<\/strong><\/p>\n\n\n\n\n\n\n\n\n\n
\n

Media<\/strong><\/p>\n<\/td>\n

\n

Test<\/strong><\/p>\n<\/td>\n

\n

Discharge flux (\u00b5g\/cm2<\/sup>\/minute)<\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

AGF pH1.2\u00b10.05<\/p>\n<\/td>\n

\n

Qusthul Hindi extract SNEDDS<\/p>\n<\/td>\n

\n

0.436 \u00b1 0.005<\/p>\n<\/td>\n<\/tr>\n

\n

Qusthul Hindi extract solution<\/p>\n<\/td>\n

\n

0.114 \u00b1 0.007<\/p>\n<\/td>\n<\/tr>\n

\n

AIF pH6.8\u00b10.05<\/p>\n<\/td>\n

\n

Qusthul Hindi extract SNEDDS<\/p>\n<\/td>\n

\n

0.405 \u00b1 0.007<\/p>\n<\/td>\n<\/tr>\n

\n

Qusthul Hindi extract solution<\/p>\n<\/td>\n

\n

0.088 \u00b1 0.002<\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

*Data are expressed as mean\u00b1SD, n=3<\/p>\n\n\n

Based on the two-way ANOVA statistical analysis of the release test flux (p=0.02), there was a significant difference between the SNEDDS and Qusthul Hindi extract solutions in AIF and AGF media.<\/p>\n\n\n\n

In Vitro Study for Absorption Testing of SNEDDS\nQusthul Hindi (Saussurea lappa<\/em>) <\/strong><\/strong><\/p>\n\n\n\n

Table 4 shows the average\namount absorbed in SNEDDS and Qusthul Hindi extract solution on AGF and AIF\nmedia. The results were then used to create a curve relating the cumulative\namount of drug absorbed to time (minutes).<\/p>\n\n\n\n\n\n
\"\"<\/td>\n\n

Figure 2: Graph of the cumulative amount of Qusthul Hindi extract (\u03bcg\/cm2<\/sup>) absorbed (time vs. the cumulative amount of drug absorbed)<\/strong><\/p>\n

\u00a0<\/p>\n

Click here to view Figure<\/a><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

\u00a0<\/p>\n\n\n

Table 4: The cumulative amount of Qusthul hindi extract (\u03bcg\/cm2<\/sup>) absorbed (p-value 0.05)<\/strong><\/p>\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n
\n

Time (minute)<\/strong><\/p>\n<\/td>\n

\n

Cumulative number of SNEDDS extracts<\/strong><\/p>\n

Qusthul Hindi absorbed (\u03bcg\/cm2<\/sup>)*<\/strong><\/p>\n<\/td>\n

\n

Cumulative amount of extract solution<\/strong><\/p>\n

Qusthul Hindi absorbed (\u03bcg\/cm2<\/sup>)*<\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

AGF 1.2 \u00b1 0.05<\/strong><\/p>\n<\/td>\n

\n

AIF 6.8 \u00b1 0.2<\/strong><\/p>\n<\/td>\n

\n

AGF 1,2 \u00b1 0,05<\/strong><\/p>\n<\/td>\n

\n

AIF 6,8 \u00b1 0,2<\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

10<\/p>\n<\/td>\n

\n

2.874 \u00b1 0.289<\/p>\n<\/td>\n

\n

1.511 \u00b1 0.166<\/p>\n<\/td>\n

\n

0.077 \u00b1 0.000<\/p>\n<\/td>\n

\n

0.077 \u00b10.000<\/p>\n<\/td>\n<\/tr>\n

\n

20<\/p>\n<\/td>\n

\n

2.898 \u00b1 0.381<\/p>\n<\/td>\n

\n

1.469 \u00b1 0.078<\/p>\n<\/td>\n

\n

0.161 \u00b1 0.005<\/p>\n<\/td>\n

\n

0.146 \u00b1 0.012<\/p>\n<\/td>\n<\/tr>\n

\n

30<\/p>\n<\/td>\n

\n

2.930 \u00b1 0.302<\/p>\n<\/td>\n

\n

1.667 \u00b1 0.156<\/p>\n<\/td>\n

\n

0.240 \u00b1 0.018<\/p>\n<\/td>\n

\n

0.210 \u00b1 0.003<\/p>\n<\/td>\n<\/tr>\n

\n

40<\/p>\n<\/td>\n

\n

3.045 \u00b1 0.545<\/p>\n<\/td>\n

\n

1.817 \u00b1 0.076<\/p>\n<\/td>\n

\n

0.320 \u00b1 0.024<\/p>\n<\/td>\n

\n

0.277 \u00b1 0.019<\/p>\n<\/td>\n<\/tr>\n

\n

50<\/p>\n<\/td>\n

\n

3.408 \u00b1 0.569<\/p>\n<\/td>\n

\n

2.544 \u00b1 0.179<\/p>\n<\/td>\n

\n

0.410 \u00b1 0.042<\/p>\n<\/td>\n

\n

0.354 \u00b1 0.018<\/p>\n<\/td>\n<\/tr>\n

\n

60<\/p>\n<\/td>\n

\n

3.611 \u00b1 0.733<\/p>\n<\/td>\n

\n

4.955 \u00b1 0.722<\/p>\n<\/td>\n

\n

0.499 \u00b1 0.047<\/p>\n<\/td>\n

\n

0.433 \u00b1 0.021<\/p>\n<\/td>\n<\/tr>\n

\n

70<\/p>\n<\/td>\n

\n

3.897 \u00b1 0.423<\/p>\n<\/td>\n

\n

7.568 \u00b1 0.117<\/p>\n<\/td>\n

\n

0.591 \u00b1 0.034<\/p>\n<\/td>\n

\n

0.519 \u00b1 0.019<\/p>\n<\/td>\n<\/tr>\n

\n

80<\/p>\n<\/td>\n

\n

4.522 \u00b1 1.262<\/p>\n<\/td>\n

\n

9.087 \u00b1 0.407<\/p>\n<\/td>\n

\n

0.687 \u00b1 0.051<\/p>\n<\/td>\n

\n

0.620 \u00b1 0.043<\/p>\n<\/td>\n<\/tr>\n

\n

90<\/p>\n<\/td>\n

\n

4.900 \u00b1 1.170<\/p>\n<\/td>\n

\n

9.267 \u00b1 0.511<\/p>\n<\/td>\n

\n

0.800 \u00b1 0.048<\/p>\n<\/td>\n

\n

0.727 \u00b1 0.023<\/p>\n<\/td>\n<\/tr>\n

\n

100<\/p>\n<\/td>\n

\n

5.018 \u00b1 1.030<\/p>\n<\/td>\n

\n

10.840 \u00b1 0.239<\/p>\n<\/td>\n

\n

0.910 \u00b1 0.056<\/p>\n<\/td>\n

\n

0.833 \u00b1 0.047<\/p>\n<\/td>\n<\/tr>\n

\n

110<\/p>\n<\/td>\n

\n

5.339 \u00b1 1.498<\/p>\n<\/td>\n

\n

11.650 \u00b1 1.117<\/p>\n<\/td>\n

\n

1.022 \u00b1 0.047<\/p>\n<\/td>\n

\n

0.947 \u00b1 0.078<\/p>\n<\/td>\n<\/tr>\n

\n

120<\/p>\n<\/td>\n

\n

5.557 \u00b1 1.652<\/p>\n<\/td>\n

\n

12.942 \u00b1 0.686<\/p>\n<\/td>\n

\n

1.136 \u00b1 0.046<\/p>\n<\/td>\n

\n

1.063 \u00b1 0.077<\/p>\n<\/td>\n<\/tr>\n

\n

130<\/p>\n<\/td>\n

\n

6.610 \u00b1 0.195<\/p>\n<\/td>\n

\n

14.240 \u00b1 0.663<\/p>\n<\/td>\n

\n

1.254 \u00b1 0.054<\/p>\n<\/td>\n

\n

1.210 \u00b1 0.066<\/p>\n<\/td>\n<\/tr>\n

\n

140<\/p>\n<\/td>\n

\n

6.592 \u00b1 0.121<\/p>\n<\/td>\n

\n

16.071 \u00b1 0.352<\/p>\n<\/td>\n

\n

1.374 \u00b1 0.043<\/p>\n<\/td>\n

\n

1.345 \u00b1 0.064<\/p>\n<\/td>\n<\/tr>\n

\n

150<\/p>\n<\/td>\n

\n

6.741 \u00b1 0.737<\/p>\n<\/td>\n

\n

16.901 \u00b1 0.385<\/p>\n<\/td>\n

\n

1.495 \u00b1 0.082<\/p>\n<\/td>\n

\n

1.483 \u00b1 0.068<\/p>\n<\/td>\n<\/tr>\n

\n

160<\/p>\n<\/td>\n

\n

9.558 \u00b1 2.443<\/p>\n<\/td>\n

\n

16.919 \u00b1 1.077<\/p>\n<\/td>\n

\n

1.642 \u00b1 0.096<\/p>\n<\/td>\n

\n

1.707 \u00b10.132<\/p>\n<\/td>\n<\/tr>\n

\n

170<\/p>\n<\/td>\n

\n

10.235 \u00b1 0.912<\/p>\n<\/td>\n

\n

17.322 \u00b1 0.755<\/p>\n<\/td>\n

\n

1.795 \u00b1 0.098<\/p>\n<\/td>\n

\n

1.925 \u00b1 0.120<\/p>\n<\/td>\n<\/tr>\n

\n

180<\/p>\n<\/td>\n

\n

9.918 \u00b1 0.792<\/p>\n<\/td>\n

\n

18.011 \u00b1 0.306<\/p>\n<\/td>\n

\n

1.967 \u00b1 0.170<\/p>\n<\/td>\n

\n

2.124 \u00b1 0.103<\/p>\n<\/td>\n<\/tr>\n

\n

190<\/p>\n<\/td>\n

\n

10.266 \u00b1 0.768<\/p>\n<\/td>\n

\n

18.512 \u00b1 1.212<\/p>\n<\/td>\n

\n

2.167 \u00b1 0.093<\/p>\n<\/td>\n

\n

2.335 \u00b1 0.108<\/p>\n<\/td>\n<\/tr>\n

\n

200<\/p>\n<\/td>\n

\n

10.110 \u00b1 1.887<\/p>\n<\/td>\n

\n

18.728 \u00b1 0.582<\/p>\n<\/td>\n

\n

2.365 \u00b1 0.190<\/p>\n<\/td>\n

\n

2.536 \u00b1 0.083<\/p>\n<\/td>\n<\/tr>\n

\n

210<\/p>\n<\/td>\n

\n

11.121 \u00b1 0.092<\/p>\n<\/td>\n

\n

19.519 \u00b1 0.859<\/p>\n<\/td>\n

\n

2.599 \u00b1 0.181<\/p>\n<\/td>\n

\n

2.768 \u00b1 0.080<\/p>\n<\/td>\n<\/tr>\n

\n

220<\/p>\n<\/td>\n

\n

12.811 \u00b1 4.084<\/p>\n<\/td>\n

\n

20.026 \u00b1 0.687<\/p>\n<\/td>\n

\n

2.821 \u00b1 0189<\/p>\n<\/td>\n

\n

3.041 \u00b1 0.071<\/p>\n<\/td>\n<\/tr>\n

\n

230<\/p>\n<\/td>\n

\n

13.516 \u00b1 0.629<\/p>\n<\/td>\n

\n

20.630 \u00b1 1.412<\/p>\n<\/td>\n

\n

3.053 \u00b1 0.184<\/p>\n<\/td>\n

\n

3.319 \u00b1 0.035<\/p>\n<\/td>\n<\/tr>\n

\n

240<\/p>\n<\/td>\n

\n

13.897 \u00b1 1.715<\/p>\n<\/td>\n

\n

20.228 \u00b1 0.729<\/p>\n<\/td>\n

\n

3.303 \u00b1 0.158<\/p>\n<\/td>\n

\n

3.599 \u00b1 0.060<\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

 *Data are expressed as mean\u00b1SD, n=3<\/p>\n\n\n

The absorption test was replicated three times for SNEDDS of qustul Hindi extract and qustul Hindi solution, which was carried out for 4 hours. The initial concentration of the extract used in the test was 67,240 \u03bcg and 66,700 \u03bcg for the SNEDDS extract of qustul Hindi. The absorbed qustul Hindi extract was calculated to obtain the cumulative amount for 4 hours. Figure 2 shows the absorption profile of qustul Hindi extract and qustul Hindi extract solution on AGF 1.2 \u00b1 0.05 and AIF 6.8 \u00b1 0.2 media. Based on the absorption profile and followed by the absorption flux calculation, Table 5 shows that SNEDDS of qustul Hindi extract provides 4.66 times higher absorption than qustul Hindi extract solution on AGF 1.2 \u00b1 0 media. 05 and AIF 6.8 \u00b1 0.2.<\/p>\n\n\n\n

Results\nof determining the average amount of qustul Hindi extract absorbed in SNEDDS qustul\nHindi extract and extract solution. Based on the absorption profile and\ncontinued absorption flux calculations, it shows that SNEDDS of qustul Hindi\nextract provides 4.66 times higher absorption compared to qustul Hindi extract\nsolution in AGF medium pH 1.2 \u00b1 0.05. The absorption data in Table 4 created a\nlinear regression equation between the cumulative amount (\u03bcg\/cm2) and the time\n(minutes) absorbed. The absorption flux value is the slope of the linear\nregression equation. The SNEDDS absorption flux value can be seen in Table 5.\nIt was obtained based on the two-way ANOVA statistical analysis of the\nabsorption test (p >0.05). This shows a significant difference between the\nSNEDDS absorption flux of qustul Hindi extract and qustul Hindi extract\nsolution in AIF medium pH 6.8 and AGF 1.2. From the results of determining the\nabsorption flux value, the reverse rat intestinal permeability value was\ncalculated for the absorbed qustul Hindi extract by dividing the absorption flux\nby the level of qustul Hindi extract used. The permeability value of the rat\nintestine to the absorbed qustul Hindi extract can be seen in Table 6. It was\nobtained based on the two-way ANOVA statistical analysis of permeability\ncalculations (p = 0.02). This shows that there is a significant difference\nbetween the intestinal permeability of inverted mice to the qustul Hindi\nextract absorbed in the qustul Hindi extract SNEDDS and the qustul Hindi\nextract solution in AGF media pH 1.2 \u00b1 0, 05 and AIF pH 6.8 \u00b1 0.05.<\/p>\n\n\n\n

Table 5: The absorption flux (\u00b5g\/cm2<\/sup>\/minute) of SNEDDS and Qusthul Hindi extract solution (Saussurea lappa<\/em>)<\/strong>.<\/p>\n\n\n\n\n\n\n\n\n\n
\n

Media<\/strong><\/p>\n<\/td>\n

\n

Test<\/strong><\/p>\n<\/td>\n

\n

Absorption flux (\u00b5g\/cm2<\/sup>\/min)<\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

AGF pH1.2\u00b10.05<\/p>\n<\/td>\n

\n

Qusthul Hindi extract SNEDDS<\/p>\n<\/td>\n

\n

0.186 \u00b1 0.002<\/p>\n<\/td>\n<\/tr>\n

\n

Qusthul Hindi extract solution<\/p>\n<\/td>\n

\n

0.038 \u00b10.001<\/p>\n<\/td>\n<\/tr>\n

\n

AIF pH6.8\u00b10.05<\/p>\n<\/td>\n

\n

Qusthul Hindi extract SNEDDS<\/p>\n<\/td>\n

\n

0.298 \u00b1 0.009<\/p>\n<\/td>\n<\/tr>\n

\n

Qusthul Hindi extract solution<\/p>\n<\/td>\n

\n

0.050 \u00b1 0.003<\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

    *Data are expressed as mean\u00b1SD, n=3<\/p>\n\n\n

Table 6: Inverted rat intestinal permeability values for SNEDDS and Qusthul Hindi (Saussurea lappa<\/em>) extract solution (cm\/minute)<\/strong>.<\/p>\n\n\n\n\n\n\n\n\n\n
\n

Media<\/strong><\/p>\n<\/td>\n

\n

Test<\/strong><\/p>\n<\/td>\n

\n

Inverted rat intestinal permeability to Qusthul hindi extract (cm\/minute)<\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

AGF pH 1.2 \u00b10.05<\/p>\n<\/td>\n

\n

Qusthul Hindi extract SNEDDS<\/p>\n<\/td>\n

\n

1.9 x10-4<\/sup>\u00b10.000<\/p>\n<\/td>\n<\/tr>\n

\n

Qusthul Hindi extract solution<\/p>\n<\/td>\n

\n

1.3 x10-4<\/sup>\u00b10.000<\/p>\n<\/td>\n<\/tr>\n

\n

AIF pH 6.8 \u00b10.05<\/p>\n<\/td>\n

\n

Qusthul Hindi extract SNEDDS<\/p>\n<\/td>\n

\n

2.2 x10-4<\/sup>\u00b10.000<\/p>\n<\/td>\n<\/tr>\n

\n

Qusthul Hindi extract solution<\/p>\n<\/td>\n

\n

1.0 x10-4<\/sup>\u00b10.000<\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

*Data are expressed as mean\u00b1SD, n=3<\/p>\n\n\n

Discussion<\/strong><\/p>\n\n\n\n

In\nthe release and absorption test, sampling in the release test and absorption\ntest started at minute 0, and this is because the release test and absorption\ntest in this study used a continuous system so that the process could not be\ninterrupted because the parameters to be measured were to determine the rate.\nThe release and absorption rates are the cumulative amounts released or\nabsorbed. Release and absorption testing is carried out in vitro, which has the\nmain advantage, namely that the experiment can be controlled precisely, and the\nvariables used are only the membrane and the material to be tested. In this\nmethod, the solution that will be tested for its dissolution and diffusion\ncapabilities under in vitro conditions must be assumed to be as follows: (1)\nThe receptor phase is in perfect “sink” condition (2) the decrease in\nconcentration in the donor is very small (3) the membrane used is a fragile and\nflat homogeneous membrane11<\/sup><\/p>\n\n\n\n

Hopefully,\nthe results of the in vitro testing in this research can be further developed\nin vivo testing. Information about in vitro-in vivo correlation (IVIVC) helps\ndevelop pharmaceutical dosage forms and new products. Regarding the development\nof SNEDDS, IVIVC data is needed and must be studied further to accurately\npredict the desired bioavailability characteristics for a control product\nrelease8<\/sup>. According to the United States Pharmacopoeia\n(USP), IVIVC establishes a rational relationship between biological properties\nor parameters obtained from biological properties produced by a dosage form and\nthe physical-chemical properties or characteristics of the same dosage form12<\/sup>. The FDA defines IVIVC as a form of a\npredictive mathematical model that describes the relationship between the in\nvitro properties of a dosage form and a relevant in vivo response. In general,\nin vitro, characteristics are the speed and amount of dissolved or dissolved\ndrug, while the in vivo response is the drug concentration in plasma or the\namount of drug absorbed8<\/sup>.<\/p>\n\n\n\n

Research\nwas conducted on the relationship between in vitro and in vivo SNEDDS testing.\nIn his study, he compared in vitro testing using Fick’s law equation and in\nvitro lipolysis with in vivo testing using white mice on the oral absorption of\nBCS class II drugs (griseofulvin (GRI), phenytoin (PHE), indomethacin (IND),\nand ketoprofen (KET)). in SNEDDS. The results of in vitro studies show that\nGRI, PHE, IND, and KET in SNEDDS increase the absorption of SNEDDS 6\u20138 times.\nMeanwhile, in vivo, GRI, PHE, IND, and KET absorption increased 15-21 times\ncompared to the suspension form. Therefore, developing SNEDDS with in vitro and\nin vivo testing can help establish correlations with oral absorption, which may\ninfluence the properties of the drug ingredients and oils in SNEDDS13<\/sup>.<\/p>\n\n\n\n

Several\nsupporting studies have proven the controlled release profile of drug compounds\nusing SNEDDS, including research into developing the SNEDDS formula design\nusing Curcumin and Piperine as medicinal ingredients. In this study, releasing qustul\nHindi extract in SNEDDS resembles research on Curcumin and Piperine in SNEDDS.\nPure curcumin without SNEDDS showed negligible % drug release (\u22480%) in both AGF\nand AIF media. Meanwhile, a significant increase in the release of Curcumin and\nPiperine (p < 0.05) occurred in the self-nanoemulsifying formulation12<\/sup>. The release date shows the release of the qustul\nHindi extract solution. Several factors influencing drug release include\nviscosity and chemical bonds of the active ingredient with the carrier. One study\nof SNEDDS formulations with the same components but using different methods\nexplained that the bioavailability of cyclosporine (CsA) in mice formed\nparticles of various sizes by administering the drug in a nanoemulsion. By\nreducing the droplet size, CsA increases oral absorption. The SNEDDS CsA test\nwas carried out on healthy volunteers with characteristic test results of\n25-400 nm particle sizes. This study showed an inverse correlation between the\nparticle size of the studied SNEDDS and the oral bioavailability of CsA12<\/sup>. Based on the results of this research, it can\nbe concluded that particle size distribution is critical because it affects the\navailability of drugs in the body after oral administration.<\/p>\n\n\n\n

Absorption\ntesting was carried out using a Wilson Crene Tube. The membrane used for the\nabsorption test was the inverted rat intestine. The test conditions were\nidentical, namely at a temperature of 37o<\/sup>C. Sampling is equalized\nfor each test, namely 1 mL. The absorption of the samples was observed using a\nUV spectrophotometer (Shimadzu UV-1800) at a maximum wavelength of 306 nm. The\nmeasured levels were corrected using the Wurster equation. After that, a curve\nwas created between the cumulative amount absorbed and time. The absorption\nprofile of the qustul Hindi extract and the qustul Hindi extract solution on\nAGF medium pH 1.2 \u00b1 0.05 and AIF pH 6.8 \u00b1 0.05 showed an increase in the\ncumulative amount of qustul Hindi extract absorbed. This happens to both SNEDDS\nof qustul Hindi extract and qustul Hindi extract solution, which shows that qustul\nHindi extract can be absorbed at a higher rate through the intestine than qustul\nHindi given in extract solution form.<\/p>\n\n\n\n

Based\non the results of the two-way ANOVA statistical analysis on the absorption\ntest, it showed that there was a significant difference between the absorption\nflux of SNEDDS of qustul Hindi extract and qustul Hindi extract solution on AIF\npH 6.8 and AGF 1 media. 2 (p=0.01). Therefore, the carrier matrix (SNEDDS)\nsignificantly increased the flux and cumulative amount of qustul Hindi extract\nabsorbed through the inverted rat intestine, which was used as a membrane in\nthe absorption test. The diffusely absorbed profile of qustul Hindi extract\ndescribes the amount of drug absorbed at a certain time interval.<\/p>\n\n\n\n

The\nabsorption process is faster in AIF media pH 6.8 \u00b1 0.2 than in AGF media pH 1.2\n\u00b1 0.2. This is probably because the pH 6.8 medium is much more alkaline than\nthe pH 1.2 AGF medium, so the qustul Hindi extract, probably a weak acid, will\ndissolve more easily. Increasing the acidity of the simulation media fluid will\nincrease the qustul Hindi extract in molecular form so that its solubility\nbecomes lower. The balance of qustul Hindi extract in a molecular and ionized\nform is better in the AIF medium pH 6.8. This causes the highest absorption of qustul\nHindi extract in the AIF medium pH 6.8. Low solubility in water and lack of\npermeability to penetrate the absorption barrier can affect the bioavailability\nof a natural compound in the body12<\/sup>. Through the SNEDDS absorption mechanism,\none of which is the formation of changes in the physical barrier function of\nthe digestive tract because the presence of SNEDDS components causes an\nincrease in permeability. The permeability of biological membranes to a drug\ncan be described by its partition coefficient as a linear relationship with its\nabsorption rate. It was obtained based on the two-way ANOVA statistical\nanalysis of permeability calculations (p=0.02). This shows a significant\ndifference between the intestinal permeability of inverted mice and the qustul Hindi\nextract absorbed in SNEDDS. Linear accumulation, or in other words, there is no\nchange due to changes in time. This discharge follows a discharge order. The\nrelease profile obtained based on this research is based on its limited ability\nto adsorb certain compounds when passing through the gastrointestinal (GI). The\napplication of SNEDDS in oral use shows that with a relatively long period of\nuse, a small dose can be given to obtain optimal results from the drug compound\nused, thereby reducing the side effects of the drug used.<\/p>\n\n\n\n

The\nrelease and absorption of SNEDDS from qustul Hindi extract follow zero order\nkinetics occurring through an interfacial transport mechanism across the\nsurfactant layer coating the emulsion droplets followed by diffusion and\nconvective transport through the surrounding aqueous medium. The release\nprocess in the nanoemulsion system occurs because the components that make up\nthe formula dissolve, causing the nanoemulsion to break and the active\nsubstance to be released. The precise kinetic\nexpression depends on (1) whether the drug enters the aqueous phase as a free\nmolecule that then \u201creacts\u201d with the micelles or enters the aqueous phase by\npartitioning directly into micelles and (2) the rate-limiting step in\ninterfacial transport, mass transport, or reaction with micelle. To explore\ndrug release influenced by the physical and chemical characteristics of the\nresulting SNEDDS formula.<\/p>\n\n\n\n

Conclusion<\/strong><\/p>\n\n\n\n

In conclusion, the selected\nformulas using Miglyol 812, Tween 80, and PEG 400 components at concentrations\nof 2.13%, 5.81%, and 2.06% were suitable as SNEDDS formulations. The SNEDDS\nformula of qusthul Hindi extract provided in vitro release flux results that\nwere 4.20 times higher in AGF media at pH 1.2 \u00b1 0.05 and 5.62 times higher in\nAIF at pH 6.8 \u00b1 0, 05 compared with a solution of the extract. The In vitro\nabsorption results also indicated a higher increase of 4.02 times in AGF and\n3.32 times higher in AIF compared to the extract solution.<\/p>\n\n\n\n

Acknowledgments<\/strong><\/p>\n\n\n\n

The authors also wish to thank the Pharmacy\nDepartment of State Islamic University, Maulana Malik Ibrahim of Malang, for\nproviding the facilities to conduct this study. <\/p>\n\n\n\n

\u00a0 Funding Sources<\/strong><\/p>\n\n\n\n

This research was funded by the\nMinistry of Religion of the Republic of Indonesia through an applied research\nscheme correlated with business and industry for the 2023 fiscal year based on\nthe decision letter of the commitment-making official from the Directorate of\nIslamic Religious Higher Education, Directorate General of Islamic Education Grant\nNumber 5377 of 2023.<\/p>\n\n\n\n

Conflict of Interest<\/strong><\/p>\n\n\n\n

  The author(s) do not have any conflict of\ninterest<\/p>\n\n\n\n

Data Availability Statement<\/strong><\/p>\n\n\n\n

This statement does not apply to this article.<\/p>\n\n\n\n

Ethics Statement<\/strong><\/p>\n\n\n\n

This research did not involve human participants, animal subjects, or any material that requires ethical approval.<\/p>\n\n\n\n

Informed Consent Statement<\/strong><\/p>\n\n\n\n

This study did not involve human participants, and therefore, informed consent was not required.<\/p>\n\n\n\n

Clinical Trial Registration<\/strong><\/p>\n\n\n\n

This research does not involve any clinical trials<\/p>\n\n\n\n

Authors\u2019 Contribution<\/strong><\/p>\n\n\n\n

Rahmi Annisa: Funding Acquisition, Resources, Supervision.<\/p>\n\n\n\n

Nabila Rahmadani, Wirda Anggraini: Data Collection, Analysis, Writing \u2013 Review & Editing.<\/p>\n\n\n\n

Avin Ainur Fitrianingsih: Data Collection, Analysis, Writing \u2013 Review & Editing.<\/p>\n\n\n\n

Roihatul Muti\u2019ah: Visualization, Supervision, Project Administration.<\/p>\n\n\n\n

Begum Fauziyah: Visualization, Supervision, Project Administration.<\/p>\n\n\n\n

Reference<\/strong><\/p>\n\n\n\n

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