# Fabrication of Direct Compressible Tablets Containing Chatuphalathika Extract Obtained through Microwave-Assisted Extraction: An Optimization Approach

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## Abstract

**:**

_{50}from DPPH assay, and IC

_{50}from FRAP assay—were monitored. Furthermore, cytotoxicity was evaluated to ensure the safety of the extract. After that, the optimized extract was compressed into tablets. The results showed that the optimal condition of the microwave-assisted extraction gave the simultaneous maximum extraction yield, total phenolic content, and antioxidant activity with a microwave power of 450 W for 30 s and 3 cycles. The extract obtained from the optimal condition exhibited a good safety profile although a concentration of 5 mg/mL was used. The optimized tablets were achieved when a compression force of 1500 psi and magnesium stearate of 1% were applied, and no sodium starch glycolate was added. In conclusion, the optimal green extraction method could be used for the extraction of the Chatuphalathika. Furthermore, the fabrication of Chatuphalathika tablets was successful, as the tablets had low friability with a short disintegration time.

## 1. Introduction

## 2. Materials and Methods

#### 2.1. Materials

_{3}·6H

_{2}O) was purchased from Merck KGaA, Frankfurter, Darmstadt, Germany. Glacial acetic acid, hydrochloric acid (HCl), and sodium acetate were purchased from Carlo Erba Reagents, Chau. du Vexin, Val-de-Reuil, France. Sodium carbonate (Na

_{2}CO

_{3}) was purchased from Ajax Finechem Pty. Ltd., Seven Hills, New South Wales, Australia. Others were analytical grade reagents and solvents. According to the pharmaceutical excipients for the tablets, microcrystalline cellulose (Comprecel

^{®}M102, Maxway Co., Ltd., Pravet, Bangkok, Thailand), magnesium stearate (Changzhou Kaide Imp. & Exp. Co., Ltd., Changzhou, Jiangsu, China), and talcum (Tabglide

^{®}, Nitika Pharmaceutical Specialities Pvt. Ltd., Civil Lines, Nagpur, India) were obtained from Sun Herb Thai Chinese Manufacturing, Muang, Pathum Thani, Thailand. Colloidal silicon dioxide was purchased from P.C. Drug Center, Khan Na Yao, Bangkok, Thailand. Sodium starch glycolate was obtained as a gift from Onimax Co., Ltd., Yannawa, Bangkok, Thailand.

#### 2.2. Plant Sample

#### 2.3. Design of Experiments and Optimization of MAE

_{1}) of 300, 450, and 600 W; duration time (X

_{2}) of 10, 20, and 30 s; and irradiation cycle (X

_{3}) of 1, 2, and 3 cycles, for low, medium, and high levels, respectively. The stop time between each cycle was 5 s. The range of MAE condition factors was based on the preliminary study. It was ensured that the MAE parameters provided no excessive boiling and were selected to vary in the experimental design [25]. The coded and experimental values of the Box–Behnken design are shown in Table 1. Eight responses—extraction yield (Y

_{1}), total phenolic content (TPC) (Y

_{2}), gallic acid content (Y

_{3}), corilagin content (Y

_{4}), chebulagic acid content (Y

_{5}), chebulinic acid content (Y

_{6}), IC

_{50}from DPPH assay (Y

_{7}), and IC

_{50}from FRAP assay (Y

_{8})—were monitored.

^{®}filter paper no. 1 by the vacuum filtration technique, allowed to cool to room temperature. It was frozen before being freeze-dried for 20–24 h. The remaining extract powder was used to calculate an extraction yield. The extracts were analyzed for their TPC by the colorimetric method; for the contents of gallic acid, corilagin, chebulagic acid, and chebulinic acid by validated high-performance liquid chromatography (HPLC); and for antioxidant activity by two colorimetric assays: DPPH and FRAP. Each measurement was performed in triplicate.

^{®}version 11 (Stat-Ease, Inc., Minneapolis, MN, USA). The three-dimensional response surfaces of each response were reported. The optimal condition provided the simultaneous highest extraction yield, TPC, and the lowest IC

_{50}values from DPPH and FRAP assays were selected based on the desirability function [26]. The prediction accuracy of the optimal condition by Design-Expert

^{®}was confirmed by re-extracting the Chatuphalathika recipe. The experimental values were compared with the predicted values, and the percentage error was calculated using Equation (1).

#### 2.4. Determination of Total Phenolic Content

_{2}CO

_{3}aqueous solution (80 μL) was added and mixed. They were further incubated at a room temperature for 1 h. Then, they were measured for absorbance at 765 nm using a microplate reader (Bio-Rad Laboratories, Inc., Hercules, CA, USA). The TPC of the plant extract was calculated from the calibration curve of gallic acid (y = 0.0059x + 0.0254, R

^{2}= 0.9990). The content of phenolic compounds of the extract was expressed as mg gallic acid equivalents (GAE) per g extract [24,25].

#### 2.5. HPLC Analysis of Gallic Acid, Corilagin, Chebulagic Acid, and Chebulinic Acid Contents

#### 2.6. Determination of Antioxidant Activity by DPPH Assay

_{blank}is the optical density of the blank and OD

_{extract}is the optical density of the extract.

#### 2.7. Determination of Antioxidant Activity by FRAP Assay

_{3}·6H

_{2}O in a volume ratio of 10:1:1, respectively, was then added and mixed. They were incubated at 37 °C for 15 min. They were measured for absorbance at 593 nm. The reducing powers were calculated using Equation (3).

_{blank}is the optical density of the blank and OD

_{extract}is the optical density of the extract.

#### 2.8. In Vitro Cytotoxicity Test

_{2}O

_{2}) was used as a positive control. Then, the culture medium was substituted with 500 µg/mL MTT solution and incubated for 3 h at 37 °C. MTT solution was then removed and 100 μL of dimethyl sulfoxide was added. It was measured using the microplate reader at 570 nm. A relative cell viability was calculated as a percentage of the vehicle control group. The average value and the standard deviation (SD) were reported [25,31].

#### 2.9. Design of Experiments, Fabrication, and Optimization of Chatuphalathika Tablets

_{1}) of 1000, 1500, and 2000 psi; the amounts of sodium starch glycolate (X

_{2}) of 0, 2, and 4%; and the amounts of magnesium stearate (X

_{3}) of 0.5, 1, and 1.5%, for low, medium, and high levels, respectively. The coded and experimental values of the Box–Behnken design are shown in Table 1.

_{1}), weight variation (Y

_{2}), thickness (Y

_{3}), diameter (Y

_{4}), hardness (Y

_{5}), friability (Y

_{6}), and disintegration time (Y

_{7})—were monitored. However, only four responses including thickness (Y

_{3}), hardness (Y

_{5}), friability (Y

_{6}), and disintegration time (Y

_{7}), were used in the optimization step.

^{®}version 11. The contour plots of each of the responses, including thickness, hardness, friability, and disintegration time, were reported. The design spaces in which friability was not more than 0.5% and disintegration time was not more than 180 s were constructed. The optimal condition was selected based on the optimization desirability function [26]; thickness and hardness were set at “none” while friability and disintegration time were set at “minimize”. The optimal condition was also considered from the condition that fell in the design space. The accuracy of the prediction by Design-Expert

^{®}was confirmed by preparing the new batch of Chatuphalathika tablets according to the optimal condition. The experimental values were compared with the predicted values and a percentage error was calculated as Equation (1).

#### 2.10. Evaluation of Chatuphalathika Tablet Properties

#### 2.10.1. Average Weight and Weight Variation

#### 2.10.2. Thickness and Diameter

#### 2.10.3. Hardness

#### 2.10.4. Friability

_{1}) using an analytical balance. Friability was tested using a friability tester (Model: CS-2, Tianjin Guoming Medicinal Equipment Co., Ltd., Hua Yuan, Tianjin, China) at 25 rpm for 4 min. Then, the tablets were removed from the drum. Dust was removed, and the tablets were weighed (W

_{2}) again. The friability was calculated using Equation (5).

#### 2.10.5. Disintegration Time

#### 2.11. Statistical Analysis

## 3. Results

#### 3.1. Extraction Yield, TPC, the Content of Some Phenolic Compounds, and Antioxidant Activity of Chatuphalathika Extracts

_{1}), chebulagic acid (Y

_{5}), and chebulinic acid (Y

_{6}) were fitted to the linear model while other responses were fitted to the quadratic model. The three-dimensional response surfaces of each response are shown in Figure 1. According to the response surfaces of the extraction yield, when the microwave power, the extraction time, and the irradiation cycle increased, the extraction yield also increased.

_{2}in Table 2, the irradiation cycle played the greatest effect on TPC, but the microwave power and the extraction time were comparatively lower than the irradiation cycle. X

_{2}X

_{3}, X

_{1}

^{2}, X

_{2}

^{2}, and X

_{3}

^{2}had a negative effect on TPC.

_{3}in Table 2, the irradiation cycle had the greatest effect on gallic acid content, followed by the extraction time and the microwave power. X

_{1}, X

_{2}, and X

_{3}had a positive effect on the gallic acid content while other interaction and quadratic terms had a negative effect on it.

_{4}in Table 2, the extraction time had a better positive effect on Y

_{4}when compared with the microwave power and the irradiation cycle. The terms X

_{1}, X

_{2}, ad X

_{3}

^{2}had a positive effect on the corilagin content, while other linear, interaction, and quadratic terms harmed the corilagin content.

_{5}and Y

_{6}in Table 2. Furthermore, perturbation plots of the Box–Behnken design for microwave-assisted extraction are shown in Figure S1 in Supplementary Materials.

_{50}, a low value was required to ensure a good antioxidant activity. The response surfaces of IC

_{50}from the DPPH and FRAP assays are shown in Figure 1. The result showed that a low IC

_{50}value obtained from the DPPH assay was achieved when a medium to high irradiation cycle was applied. Meanwhile, a low IC

_{50}value obtained from the FRAP assay was achieved when a low or high irradiation cycle was applied. According to the equation of Y

_{7}in Table 2, a good antioxidant activity (or low IC

_{50}value) based on the DPPH assay was achieved by X

_{2}, X

_{3}, and X

_{1}

^{2}. Meanwhile, a good antioxidant activity based on the FRAP assay was achieved by X

_{1}, X

_{1}X

_{2}, X

_{1}X

_{3}, X

_{2}X

_{3}, and X

_{3}

^{2}.

#### 3.2. Optimal Condition of MAE

_{1}) and TPC (Y

_{2})—were set at “maximize”, while IC

_{50}from the DPPH assay (Y

_{7}) and IC

_{50}from the FRAP assay (Y

_{8}) were set at “minimize”, with a microwave power of 450 W for 30 s and repeated for 3 cycles. The gallic acid, corilagin, chebulagic acid, and chebulinic acid contents (Y

_{3}to Y

_{6}) were not used in the optimization process because the TPC (Y

_{2}) covered the Y

_{3}to Y

_{6}. Verification of the predicted optimal condition was performed to ensure the accuracy of the prediction of computer software. The percentage prediction error of all responses was less than 15%. The percentage error seemed to be relatively high due to the small value that caused a huge percentage error. However, the research suggested that all experimental values were close to the predicted values (Table 3).

#### 3.3. In Vitro Cytotoxicity

_{50}values of both extracts could not be determined from the study (Figure 4). A significant decrease in the cell viability in the presence of Chatuphalathika extract was observed at a concentration of 0.0001 mg/mL, and the cell viability further decreased up to a concentration of 5 mg/mL, compared with the non-treated group. Meanwhile, the positive control, 200 μM hydrogen peroxide, yielded a cell viability of only 62.82 ± 0.64% (Figure 4).

#### 3.4. Optimal Fabricated Chatuphalathika Tablets

_{1}), the weight variation (Y

_{2}), and the diameter (Y

_{4}), the average weight per tablet was about 600 mg with a diameter of 12.7 mm. No tablets had a weight variation of more than 5% of the average weight. The factors and responses of the Box–Behnken design for tablet fabrication are shown in Table S2 in Supplementary Materials. Among the optimized responses, the tablet thickness (Y

_{3}), friability (Y

_{6}), and disintegration time (Y

_{7}) were fitted to the quadratic model while hardness (Y

_{5}) was fitted to the linear model. The contour plots of the four responses of the fabricated tablets are shown in Figure 5. Furthermore, perturbation plots of the Box–Behnken design for tablet fabrication are shown in Figure S2 in Supplementary Materials. When compression force increased, tablet thickness and friability decreased, whereas hardness and disintegration time increased in all levels of magnesium stearate. An increasing amount of sodium starch glycolate seemed to have no effect on tablet thickness, hardness, and disintegration time, but increased tablet friability. The amount of magnesium stearate had more effect on tablet friability than the disintegration time and thickness. However, it seemed to have no effect on tablet hardness. According to the equation in Table 4, the terms that decreased tablet thickness (Y

_{3}) were X

_{1}, X

_{2}, X

_{1}X

_{3}, and X

_{3}

^{2}. The terms X

_{1}and X

_{3}increased tablet hardness (Y

_{5}) while X

_{2}decreased Y

_{5}. The terms decreasing tablet friability (Y

_{6}) were X

_{1}, X

_{1}X

_{2}, and X

_{1}X

_{3}, while the others increased tablet friability. The terms that shortened the disintegration time (Y

_{7}) were X

_{1}, X

_{2}, X

_{3}, X

_{2}X

_{3}, and X

_{2}

^{2}. Among these terms, X

_{3}affected Y

_{7}the most.

## 4. Discussion

_{50}value of 77.63 µg/mL, which was close to the IC

_{50}values of P. emblica and T. chebula, while T. bellirica had an IC

_{50}value of 129.3 µg/mL [40]. The clinical trial showed that Triphala aqueous extract is safe for healthy volunteers, raises HDL-C levels, and decreases blood sugar [41]. However, the present work revealed that Chatuphalathika extracts had no toxic effects on HepG2 cells even though a high concentration of up to 5 mg/mL was used.

_{1}X

_{2}) seemed to increase the disintegration time but decrease friability.

_{2}

^{2}) decreased the disintegration time. Furthermore, the interaction of sodium starch glycolate and magnesium stearate (X

_{2}X

_{3}) decreased the disintegration time while increasing friability. Nevertheless, the fabricated Chatuphalathika tablets rapidly disintegrated naturally, so sodium starch glycolate was unnecessary for this formulation. Magnesium stearate is a lubricant used to decrease friction forces between particles [50]. Because of its hydrophobic property, it could prolong the disintegration time [50], especially when a high compression force was applied, as found in this research.

## 5. Conclusions

## Supplementary Materials

_{50}from DPPH assay, and (h) IC

_{50}from FRAP assay; Figure S2: Perturbation plots of each response of the Box–Behnken design for tablet fabrication; (a) tablet thickness, (b) hardness, (c) friability, and (d) disintegration time.

## Author Contributions

## Funding

## Institutional Review Board Statement

## Informed Consent Statement

## Data Availability Statement

## Acknowledgments

## Conflicts of Interest

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**Figure 1.**Response surfaces of extraction yield, TPC, IC

_{50}from DPPH assay, and IC

_{50}from FRAP assay when the irradiation cycle was (

**a**) low, (

**b**) medium, and (

**c**) high.

**Figure 2.**HPLC chromatogram of the Chatuphalathika extract obtained from the optimal condition (2 mg/mL).

**Figure 3.**Response surfaces of gallic acid, corilagin, chebulagic acid, and chebulinic acid contents when the irradiation cycle was (

**a**) low, (

**b**) medium, and (

**c**) high.

**Figure 4.**In vitro cytotoxicity of Chatuphalathika extracts in HepG2 cells compared with the non-treated (NT) group and the positive control group (200 μM hydrogen peroxide). The significance is presented as ** and *** when p < 0.01 and p < 0.001, respectively.

**Figure 5.**Contour plots of tablet thickness, hardness, friability, and disintegration time when the amount of magnesium stearate was (

**a**) low, (

**b**) medium, and (

**c**) high.

**Figure 6.**Design spaces in which friability was not more than 0.5% and the disintegration time was not more than 180 s when the amount of magnesium stearate was (

**a**) low, (

**b**) medium, and (

**c**) high.

**Table 1.**Coded values and experimental values of the Box–Behnken design: for microwave-assisted extraction, X

_{1}is the microwave power, X

_{2}is the duration time, and X

_{3}is the irradiation cycle for microwave-assisted extraction; and for tablet fabrication, X

_{1}is the compression force, X

_{2}is the amount of sodium starch glycolate, and X

_{3}is the amount of magnesium stearate.

Factors | Levels * | ||
---|---|---|---|

−1 | 0 | +1 | |

Microwave-assisted extraction | |||

X_{1} (W) | 300 | 450 | 600 |

X_{2} (s) | 10 | 20 | 30 |

X_{3} (cycle) | 1 | 2 | 3 |

Tablet fabrication | |||

X_{1} (psi) | 1000 | 1500 | 2000 |

X_{2} (%) | 0 | 2 | 4 |

X_{3} (%) | 0.5 | 1.0 | 1.5 |

Responses | Models | Equations * |

Y_{1} (%) | Linear | ${Y}_{1}=2.54+0.01{\mathit{X}}_{\mathbf{1}}+0.43{\mathit{X}}_{\mathbf{2}}+4.96{X}_{3}$ |

Y_{2} (mg GAE/g extract) | Quadratic | ${Y}_{2}=103.03+0.90{X}_{1}+1.60{X}_{2}+50.98{\mathit{X}}_{\mathbf{3}}+\left(1.19\times {10}^{-3}\right){X}_{1}{X}_{2}+0.10{X}_{1}{X}_{3}-0.74{X}_{2}{X}_{3}-\left(1.31\times {10}^{-3}\right){\mathit{X}}_{\mathbf{1}}^{\mathbf{2}}-\left(4.79\times {10}^{-3}\right){X}_{2}^{2}-12.12{X}_{3}^{2}$ |

Y_{3} (%) | Quadratic | ${Y}_{3}=-4.37+0.03{X}_{1}+0.19{X}_{2}+1.19{\mathit{X}}_{\mathbf{3}}-\left(0.14\times {10}^{-3}\right){X}_{1}{X}_{2}-\left(0.51\times {10}^{-3}\right){X}_{1}{X}_{3}-0.03{\mathit{X}}_{\mathbf{2}}{\mathit{X}}_{\mathbf{3}}-\left(0.03\times {10}^{-3}\right){\mathit{X}}_{\mathbf{1}}^{\mathbf{2}}-\left(1.88\times {10}^{-3}\right){X}_{2}^{2}-0.15{X}_{3}^{2}$ |

Y_{4} (%) | Quadratic | ${Y}_{4}=0.21+\left(2.57\times {10}^{-3}\right){\mathit{X}}_{\mathbf{1}}+0.05{\mathit{X}}_{\mathbf{2}}-0.30{X}_{3}-\left(0.03\times {10}^{-3}\right){\mathit{X}}_{\mathbf{1}}{\mathit{X}}_{\mathbf{2}}-\left(0.08\times {10}^{-3}\right){X}_{1}{X}_{3}-\left(0.39\times {10}^{-3}\right){X}_{2}{X}_{3}-\left(1.61\times {10}^{-6}\right){X}_{1}^{2}-\left(0.74\times {10}^{-3}\right){\mathit{X}}_{\mathbf{2}}^{\mathbf{2}}+0.09{\mathit{X}}_{\mathbf{3}}^{\mathbf{2}}$ |

Y_{5} (%) | Linear | ${Y}_{5}=1.22+\left(2.96\times {10}^{-3}\right){\mathit{X}}_{\mathbf{1}}+0.06{\mathit{X}}_{\mathbf{2}}+0.87{\mathit{X}}_{\mathbf{3}}$ |

Y_{6} (%) | Linear | ${Y}_{6}=3.36+\left(2.05\times {10}^{-3}\right){X}_{1}+0.06{\mathit{X}}_{\mathbf{2}}+0.25{X}_{3}$ |

Y_{7} (μg/mL) | Quadratic | ${Y}_{7}=77.76+0.08{X}_{1}-2.67{X}_{2}-51.12{\mathit{X}}_{\mathbf{3}}+\left(0.31\times {10}^{-3}\right){X}_{1}{X}_{2}+0.02{X}_{1}{X}_{3}+0.50{X}_{2}{X}_{3}-\left(0.15\times {10}^{-3}\right){X}_{1}^{2}+0.03{X}_{2}^{2}+6.56{\mathit{X}}_{\mathbf{3}}^{\mathbf{2}}$ |

Y_{8} (μg/mL) | Quadratic | ${Y}_{8}=10.07-0.03{X}_{1}+0.26{\mathit{X}}_{\mathbf{2}}+11.22{X}_{3}-\left(2.85\times {10}^{-3}\right){\mathit{X}}_{\mathbf{1}}{\mathit{X}}_{\mathbf{2}}-(0.06\times {10}^{-3}){X}_{1}{X}_{3}-0.03{X}_{2}{X}_{3}+\left(0.10\times {10}^{-3}\right){\mathit{X}}_{\mathbf{1}}^{\mathbf{2}}+0.03{\mathit{X}}_{\mathbf{2}}^{\mathbf{2}}-2.63{\mathit{X}}_{\mathbf{3}}^{\mathbf{2}}$ |

Responses * | Predicted Values | Experimental Values ** | Percentage Error (%) |
---|---|---|---|

Y_{1} (%) | 35.46 | 37.77 ± 0.60 | 6.12 |

Y_{2} (mg GAE/g extract) | 417.80 | 421.90 ± 6.19 | 0.97 |

Y_{7} (μg/mL) | 15.97 | 14.65 ± 0.87 | −9.01 |

Y_{8} (μg/mL) | 15.17 | 13.39 ± 0.64 | −13.29 |

_{1}is the extraction yield, Y

_{2}is the TPC, Y

_{7}is the IC

_{50}from the DPPH assay, and Y

_{8}is the IC

_{50}from the FRAP assay. ** The data are presented as mean ± SD.

Responses | Models | Equations * |
---|---|---|

Y_{3} (mm) | Quadratic | ${Y}_{3}=6.14-\left(1.96\times {10}^{-3}\right){\mathit{X}}_{\mathbf{1}}-0.10{X}_{2}+0.26{X}_{3}+\left(2.00\times {10}^{-5}\right){X}_{1}{X}_{2}-(1.30\times {10}^{-4}){X}_{1}{X}_{3}+0.01{X}_{2}{X}_{3}+\left(4.83\times {10}^{-7}\right){\mathit{X}}_{\mathbf{1}}^{\mathbf{2}}+0.01{X}_{2}^{2}-0.09{X}_{3}^{2}$ |

Y_{5} (kP) | Linear | ${Y}_{5}=-4.75+\left(5.44\times {10}^{-3}\right){\mathit{X}}_{\mathbf{1}}-0.06{X}_{2}+1.18{X}_{3}$ |

Y_{6} (%) | Quadratic | ${Y}_{6}=9.99-0.06{\mathit{X}}_{\mathbf{1}}+12.00{\mathit{X}}_{\mathrm{2}}+46.63{\mathit{X}}_{\mathbf{3}}-0.02{\mathit{X}}_{\mathbf{1}}{\mathit{X}}_{\mathbf{2}}-0.10{\mathit{X}}_{\mathbf{1}}{\mathit{X}}_{\mathbf{3}}+24.66{\mathit{X}}_{\mathbf{2}}{\mathit{X}}_{\mathbf{3}}+\left(5.00\times {10}^{-5}\right){\mathit{X}}_{\mathbf{1}}^{\mathbf{2}}+3.02{\mathit{X}}_{\mathbf{2}}^{\mathbf{2}}+49.05{\mathit{X}}_{\mathbf{3}}^{\mathbf{2}}$ |

Y_{7} (s) | Quadratic | ${Y}_{7}=1236.53-1.53{\mathit{X}}_{\mathbf{1}}-7.01{X}_{2}-694.63{X}_{3}+0.01{X}_{1}{X}_{2}+0.47{\mathit{X}}_{\mathbf{1}}{\mathit{X}}_{\mathbf{3}}-6.48{X}_{2}{X}_{3}+\left(4.69\times {10}^{-4}\right){\mathit{X}}_{\mathbf{1}}^{\mathbf{2}}-0.56{X}_{2}^{2}+66.95{X}_{3}^{2}$ |

Responses * | Predicted Values | Experimental Values ** | Percentage Error (%) |
---|---|---|---|

Y_{3} (mm) | 4.28 | 4.30 ± 0.06 | 0.93 |

Y_{5} (kP) | 4.58 | 4.30 ± 0.50 | −6.51 |

Y_{6} (%) | 0.00 | 0.37 | 100 |

Y_{7} (s) | 77.62 | 75.26 ± 9.62 | −3.14 |

_{3}is the tablet thickness, Y

_{5}is the tablet hardness, Y

_{6}is the friability, and Y

_{7}is the disintegration time. ** The data are presented as mean ± SD.

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## Share and Cite

**MDPI and ACS Style**

Monton, C.; Keawchay, P.; Pokkrong, C.; Kamnoedthapaya, P.; Navabhatra, A.; Suksaeree, J.; Wunnakup, T.; Chankana, N.; Songsak, T. Fabrication of Direct Compressible Tablets Containing Chatuphalathika Extract Obtained through Microwave-Assisted Extraction: An Optimization Approach. *Sci. Pharm.* **2023**, *91*, 17.
https://doi.org/10.3390/scipharm91020017

**AMA Style**

Monton C, Keawchay P, Pokkrong C, Kamnoedthapaya P, Navabhatra A, Suksaeree J, Wunnakup T, Chankana N, Songsak T. Fabrication of Direct Compressible Tablets Containing Chatuphalathika Extract Obtained through Microwave-Assisted Extraction: An Optimization Approach. *Scientia Pharmaceutica*. 2023; 91(2):17.
https://doi.org/10.3390/scipharm91020017

**Chicago/Turabian Style**

Monton, Chaowalit, Piyapa Keawchay, Chantisa Pokkrong, Pariyakorn Kamnoedthapaya, Abhiruj Navabhatra, Jirapornchai Suksaeree, Thaniya Wunnakup, Natawat Chankana, and Thanapat Songsak. 2023. "Fabrication of Direct Compressible Tablets Containing Chatuphalathika Extract Obtained through Microwave-Assisted Extraction: An Optimization Approach" *Scientia Pharmaceutica* 91, no. 2: 17.
https://doi.org/10.3390/scipharm91020017