Physalis alkekengi calyx extract effervescent tablet as well as preparation process and quality evaluation thereof

Abstract

The invention discloses a physalis alkekengi calyx extract effervescent tablet as well as a preparation process and quality evaluation thereof. The effervescent tablet comprises the following extracts and auxiliary materials in percentage by weight: 7-12% of physalis alkekengi calyx extract, and the auxiliary materials comprising 50% of total acid and alkali (the ratio of acid to alkali is 0.6: 1-1.4: 1), 5-15% of a lubricant, 1-5% of a sweetening agent, 2-10% of an adhesive and the balance of a filling agent, totaling 100%. The invention provides a preparation method of the physalis alkekengi calyx extract effervescent tablet powder by a direct tabletting method, and the process comprises the following steps: uniformly mixing and grinding a lubricant and sodium bicarbonate, adding the ground citric acid, the physalis alkekengi calyx extract, an adhesive, a sweetening agent and a filling agent, uniformly mixing, and tabletting. After the process is optimized, the disintegration time limit of the obtained effervescent tablets meets the requirements of pharmacopeia, and the tablet weight difference is qualified. The method is simple, convenient, feasible, stable and reliable, and the prepared effervescent tablets are rapid in disintegration, good in taste and stable in quality and have high clinical application value and market prospects.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine preparation technology, specifically to an effervescent tablet of Phyllanthus urinaria calyx extract and its preparation process and quality evaluation. Background Technology

[0002] Physalis alkekengi L. var. francheetii (Mast.) Makino, also known as Chinese ground cherry, is the dried persistent calyx or fruit-bearing persistent calyx of the plant Physalis alkekengi L. var. francheetii (Mast.) Makino, belonging to the Solanaceae family. It is a perennial herb named for its unique lantern-like shape caused by the persistent calyx covering its fruit. It is widely distributed in Jilin, Xinjiang, and Hebei provinces of China. Physalis alkekengi has been used in medicine for nearly two thousand years. The 2020 edition of the Chinese Pharmacopoeia records that it is cold in nature and bitter in taste, entering the lung meridian, and possesses multiple effects such as clearing heat and detoxifying, relieving sore throat and resolving phlegm, and promoting urination. In traditional Chinese medicine, Physalis alkekengi combined with Shuanghuanglian (a traditional Chinese medicine formula) can be used to treat herpetic pharyngitis in children; Physalis alkekengi injection is used to treat upper respiratory tract infections in children; and Physalis alkekengi decoction can treat bacterial dysentery. It is a highly valued and commonly used traditional Chinese medicine that is both food and medicine.

[0003] Physalis alkekengi was first recorded in the *Shennong Bencao Jing* (Shennong's Classic of Materia Medica). As a traditional Chinese medicine, Physalis alkekengi has a long history of medicinal use, and its use is also documented in many classic texts such as the *Compendium of Materia Medica*, *Erya*, and *Supplement to the Compendium of Materia Medica*. The chemical components of Physalis alkekengi mainly include steroids, flavonoids, terpenes, sugars and glycosides, nitrogenous compounds, and phenolic acids. With further research, these components have been found to possess more modern pharmacological activities, such as antibacterial, anti-inflammatory, antioxidant, anti-mycoplasma, hypoglycemic, and antitumor effects.

[0004] Traditional dosage forms of *Phyllanthus urinaria* (Chinese lantern) suffer from limitations such as inconvenient administration and low bioavailability, restricting its clinical application. Effervescent tablets, as a novel dosage form, offer advantages such as rapid disintegration, convenient administration, and high bioavailability, showing broad application prospects in the field of traditional Chinese medicine extract preparations. Effervescent tablets are tablets made by adding disintegrants to the raw materials. Upon dissolving in water, they rapidly disintegrate, producing a large amount of gas and exhibiting an effervescent appearance. During disintegration, some of the released carbon dioxide dissolves in the water, giving the solution a soda-like taste, which is widely popular. The advantages of effervescent tablets include: ready to drink, practicality, portability, high safety, and greater appeal compared to other tablets, better meeting the purchasing desires and preferences of modern consumers. Effervescent tablets are less prone to leakage during transportation and storage, aligning with the development trend of high efficiency, safety, and convenience. Currently, there are no research or products on effervescent tablets containing *Phyllanthus urinaria* calyx extract. Therefore, developing an effervescent tablet containing *Phyllanthus urinaria* calyx extract and its preparation process has significant clinical practical value and social benefits. Summary of the Invention

[0005] To address the aforementioned problems, the present invention aims to provide an effervescent tablet of *Phyllanthus urinaria* calyx extract, its preparation process, and quality evaluation, thereby overcoming the deficiencies of existing *Phyllanthus urinaria* dosage forms and fully utilizing its medicinal value. The objective of this invention is achieved through the following technical solution: an effervescent tablet of *Phyllanthus urinaria* calyx extract, its preparation process, and quality evaluation, comprising the following steps:

[0006] Polyethylene glycol 6000 was mixed with sodium bicarbonate and passed through a 100-mesh sieve. Citric acid, Physalis alkekengi extract powder, polyvinylpyrrolidone, sucralose and mannitol were each passed through a 100-mesh sieve. All materials were thoroughly mixed and then compressed into tablets.

[0007] The preparation method of the Physalis extract includes the following steps:

[0008] The calyx of *Phyllostachys edulis* was dried, cut into small pieces, and then extracted with 70% ethanol at a solid-liquid ratio of 1:4. The mixture was refluxed at 80°C for 2 hours, filtered, and the extraction was repeated twice. The filtrates were combined, concentrated, and freeze-dried to obtain *Phyllostachys edulis* calyx extract powder.

[0009] An effervescent tablet containing *Phyllostachys edulis* calyx extract, the tablet comprising 100% by weight. It consists of the following components by weight percentage: 7-12% *Phyllostachys edulis* calyx extract, 50% total disintegrant (acid-base ratio 0.6:1-1.4:1), 5%-15% polyethylene glycol 6000 (lubricant), 1%-5% sucralose (sweetener), 2%-10% polyvinylpyrrolidone (binder), and mannitol (filler) to bring the total to 100%.

[0010] Preferably, an effervescent tablet containing *Lysimachia foenum-graecum* extract is composed of the following raw materials in parts by weight: 20% *Lysimachia foenum-graecum* extract, 50% disintegrant, 10% lubricant, 4% sweetener, 6% binder, and 10% filler.

[0011] The acid source in the disintegrant is citric acid, and the base source is sodium bicarbonate, with a preferred ratio of 0.8:1.

[0012] The lubricant is polyethylene glycol 6000.

[0013] The sweetener is sucralose.

[0014] The adhesive is polyvinylpyrrolidone.

[0015] The filler is mannitol.

[0016] A method for preparing effervescent tablets of Physalis alkekengi extract includes the following steps: polyethylene glycol 6000 is mixed with sodium bicarbonate, passed through a 100-mesh sieve, and dried in a drying oven. Citric acid, Physalis alkekengi calyx extract, polyvinylpyrrolidone, sucralose, and mannitol are mixed evenly, passed through a 100-mesh sieve, and dried in a drying oven. The two materials are then evenly mixed and compressed into tablets.

[0017] The advantages of this invention are:

[0018] 1. This invention provides an effervescent tablet of *Phyllanthus urinaria* calyx extract; the effervescent tablet of *Phyllanthus urinaria* calyx extract has good effervescent effect, rapid disintegration, and good taste, and can improve the bioavailability of the drug.

[0019] 2. Optimized formulation to ensure product performance: By screening formulation factors such as the ratio of acid-base disintegrants, the amount of flavoring agents, the amount of lubricants, and the amount of binders, the optimal formulation and process were determined. The disintegration time of the prepared *Phyllanthus urinaria* calyx extract effervescent tablets meets the requirements of the 2025 edition of the Chinese Pharmacopoeia.

[0020] This preparation process employs direct powder compression, which is simple, highly efficient, and avoids the influence of humid and hot environments on drug components, thus ensuring drug stability. During preparation, raw materials and excipients undergo pretreatment, such as passing them through a 100-mesh sieve, resulting in a clear solution with minimal sedimentation after disintegration, improving solution clarity and taste. Attached Figure Description

[0021] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0022] Figure 1 This is a schematic diagram comparing the moisture absorption rates of citric acid and tartaric acid in effervescent tablets of *Lysimachia nummularia* calyx extract in an embodiment of the present invention.

[0023] Figure 2 This is a schematic diagram comparing the sensory scores of citric acid and tartaric acid in the effervescent tablets of the calyx extract of *Lysimachia nummularia* in an embodiment of the present invention.

[0024] Figure 3 This is a graph showing the effect of the disintegrant ratio on pH value of the effervescent tablets of *Lysimachia foenum-graecum* extract in an embodiment of the present invention.

[0025] Figure 4 This is a schematic diagram illustrating the effect of the disintegrant ratio on the disintegration time of the effervescent tablets containing the extract of *Lysimachia nummularia* in an embodiment of the present invention.

[0026] Figure 5 This is a schematic diagram illustrating the effect of the disintegrant ratio on sensory scores of the effervescent tablets containing the extract of Phyllanthus urinaria in an embodiment of the present invention.

[0027] Figure 6 This is a schematic diagram illustrating the effect of the amount of disintegrant in the effervescent tablets of *Lysimachia foenum-graecum* extract on sensory scores in an embodiment of the present invention.

[0028] Figure 7 This is a schematic diagram illustrating the effect of the amount of disintegrant used on the disintegration time of the effervescent tablets containing the extract of *Lysimachia nummularia* in an embodiment of the present invention.

[0029] Figure 8 This is a schematic diagram of the response surface three-dimensional relationship and contour plot of the effect of various interaction terms of the calyx extract effervescent tablets on the disintegration time in an embodiment of the present invention.

[0030] Figure 9 This is a schematic diagram of the response surface three-dimensional relationship and contour plot of the influence of various interaction terms of the effervescent tablets of Phyllanthus urinaria extract on sensory scores in an embodiment of the present invention. Detailed Implementation

[0031] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0032] In the current field of preparation technology for effervescent tablets of *Caragana korshinskii* extract, the direct powder compression method is widely used. Compared with many other methods such as wet granulation and dry granulation, this method has significant advantages. Its process is relatively simple, without the need for granulation and drying steps, and can achieve stable molding of *Caragana korshinskii* extract. It also has lower requirements for production equipment and can adapt to the needs of large-scale production. It occupies an extremely important position in the formulation research and industrialization process of *Caragana korshinskii* extract, and lays a solid and reliable technical foundation for the subsequent industrial production and clinical application of related effervescent tablet products.

[0033] Based on existing technologies, the preparation process and quality control methods of existing effervescent tablets containing Phyllanthus urinaria calyx extract have the following problems: the resulting effervescent tablets are easily affected by environmental humidity, there is a lot of precipitation in the solution after disintegration, and the preparation process is complicated due to the strict requirements on the ratio of excipients.

[0034] Example 1

[0035] See Figure 1 , Figure 2 , Figure 3 , Figure 4 , Figure 5 , Figure 6 , Figure 7 , Figure 8 , Figure 9 This embodiment provides an effervescent tablet of Phyllanthus urinaria calyx extract, its preparation process, and quality evaluation.

[0036] Instruments: UV1200 UV-Vis spectrophotometer; RE-52AA rotary evaporator; 101-2AB electric heating drying oven; GK-70 rotary multi-punch tablet press.

[0037] Medicinal materials and reagents: Phyllanthus urinaria calyx. Citric acid, sodium bicarbonate, D-mannitol, polyethylene glycol 6000, sucralose, polyvinylpyrrolidone, ethanol. All are food grade.

[0038] Table 1 Sensory Evaluation Criteria for Effervescent Tablets

[0039]

[0040]

[0041] Example 1: Preparation of extract from the calyx of *Phyllanthus urinaria*

[0042] The calyxes of *Phyllostachys edulis* were dried, cut into small pieces, and 70% ethanol was added to them at a material-to-liquid ratio of 1:4. The mixture was refluxed at 80°C for 2 hours, filtered, and the process was repeated twice. The filtrates were combined, concentrated, and freeze-dried to obtain the *Phyllostachys edulis* calyx extract.

[0043] Example 2: A method for preparing effervescent tablets of *Phyllostachys edulis* calyx extract: 5-15% polyethylene glycol 6000 and sodium bicarbonate (citric acid to sodium bicarbonate ratio of 0.6:1-1.4:1, total acid-base content of 50%) were mixed, passed through a 100-mesh sieve, and dried in a drying oven. Citric acid (citric acid to sodium bicarbonate ratio of 0.6:1-1.4:1, total acid-base content of 50%), 10% *Phyllostachys edulis* calyx extract, 6% polyvinylpyrrolidone, and 4% sucralose were each passed through a 100-mesh sieve, mixed evenly, and dried in a drying oven. The two materials were then uniformly mixed and compressed into tablets. The average weight of each prepared effervescent tablet was 1.0g.

[0044] 1. Screening of fillers

[0045] As the main excipient in effervescent tablets, the filler primarily serves to dilute the tablet components and fill the tablet's weight and volume, thus facilitating tablet compression. Its hygroscopic effect was examined; high hygroscopicity can lead to tablet failure during storage, therefore a filler with lower hygroscopicity was selected. The hygroscopicity of 5g of soluble starch and mannitol after 24, 48, 72, and 96 hours is shown in Table 2. Mannitol showed a lower hygroscopicity at the same time, and while the total extract of *Physalis alkekengi* has a bitter taste, mannitol has flavor-regulating properties; therefore, mannitol was chosen as the filler for this effervescent tablet.

[0046] Table 2. Screening of filler types

[0047]

[0048] 2. Screening of acid sources

[0049] The acid sources investigated were citric acid and tartaric acid. Accurately weighed 5g each of tartaric acid and citric acid were placed in air for 24, 48, 72, and 96 hours, and their moisture absorption rates were measured. Figure 1 and Figure 2 It is known that citric acid has a significantly higher hygroscopicity than tartaric acid, and its foaming capacity is also significantly higher. Insufficient foaming capacity will lead to a prolonged disintegration time of the effervescent tablets. Citric acid also has a significantly higher sensory score than tartaric acid. Therefore, citric acid was chosen as the acid source.

[0050] 3. Determination of sweeteners

[0051] The chosen sweetener is sucralose, which boasts advantages such as high sweetness, no calories, no blood sugar spikes, and high safety. Sucrose is also a common sweetener with many beneficial effects, such as promoting calcium absorption, and is readily available and inexpensive. The calyx extract of *Phyllanthus urinaria* has a bitter taste; to neutralize this flavor, a higher amount of sucrose is required than sucralose. Therefore, sucralose was chosen as the sweetener for *Phyllanthus urinaria* total extract effervescent tablets.

[0052] 4. Effect of acid-base ratio on disintegration time and pH of effervescent tablets.

[0053] Citric acid and sodium bicarbonate were selected as disintegrants, with an addition amount of 50%; *Phyllanthus urinaria* calyx extract powder was added at 10%; PEG6000 was added as a lubricant at 10%; polyvinylpyrrolidone was added as a binder at 6%; sucralose was added as a sweetener at 4%; and mannitol was added as a filler to bring the total to 100%. The ratio of effervescent disintegrants has a significant impact on the disintegration rate and taste of effervescent tablets. When the proportion of acid sources is high, the effervescent tablets taste more acidic, while when the proportion of alkali sources is high, the effervescent tablets taste more bitter and the color is darker, affecting the overall taste of the effervescent tablets. A suitable acid-base ratio is necessary. Single-factor experiments were conducted with effervescent agent ratios of 0.6:1, 0.8:1, 1:1, 1.2:1, and 1.4:1, and the results are as follows. Figure 3 , 4 As shown in Figure 5.

[0054] As the acid-base ratio of the effervescent disintegrant gradually increases, the pH of the effervescent tablet after disintegration shows a gradual decreasing trend. Figure 3 ).Depend on Figure 4 It can be seen that the disintegration time exhibits a trend of first decreasing and then significantly increasing, which is consistent with... Figure 5 The sensory evaluation trends were consistent. At an acid-base ratio of 0.8:1, the total extract effervescent tablets of *Phyllanthus urinaria* exhibited the shortest disintegration time (151 seconds), achieving a sensory score of 71 points and reaching optimal taste, possessing the unique aroma of *Phyllanthus urinaria* and a pleasantly sweet and sour flavor. At an acid-base ratio of 0.6:1, the effervescent tablets exhibited a bitter taste, which disappeared with increasing acidity. At disintegrant ratios of 1.2:1 and 1.4:1, the total extract effervescent tablets of *Phyllanthus urinaria* showed a slightly acidic taste. Therefore, when the ratio of citric acid to sodium bicarbonate was 0.8:1, the total extract effervescent tablets of *Phyllanthus urinaria* had the best taste, with a balanced sweet and sour flavor. Thus, the disintegrant in the effervescent tablets was determined to be a citric acid to sodium bicarbonate ratio of 0.8:1.

[0055] 5. Determination of the dosage of effervescent disintegrant

[0056] Citric acid and sodium bicarbonate were selected as disintegrants in a ratio of 0.8:1. 10% total extract powder of *Phyllostachys edulis* was added, PEG6000 was added as a lubricant at 10%, polyvinylpyrrolidone as a binder at 6%, sucralose as a sweetener at 4%, and mannitol as a filler, to be added to 100%. 0.2g, 0.3g, 0.4g, 0.5g, and 0.6g of citric acid and sodium bicarbonate were weighed out separately, with a disintegrant ratio of 0.8:1. PEG6000 and sodium bicarbonate were mixed, passed through a 100-mesh sieve, and dried in a drying oven. Citric acid, *Phyllostachys edulis* extract, polyvinylpyrrolidone, and sucralose were mixed evenly, passed through a 100-mesh sieve, and dried in a drying oven. The two materials were then evenly mixed and compressed into tablets. 200ml of distilled water was placed in a beaker. Sensory evaluation, pH, and disintegration time of the total extract effervescent tablet solution of Physalis alkekengi were determined, and the results are as follows: Figure 6 and Figure 7 As shown.

[0057] Depend on Figure 6 It can be seen that as the amount of effervescent disintegrant added gradually increases, the sensory score of the *Phyllostachys edulis* calyx extract effervescent tablets shows a trend of first increasing and then decreasing. When the amount of disintegrant added is 0.5g, the sensory score of the *Phyllostachys edulis* calyx extract effervescent tablets reaches its maximum, with a rich taste and unique flavor. As the amount of disintegrant added gradually increases, the taste of the effervescent tablets becomes bitter. Figure 7 It can be seen that as the disintegrant is added, the disintegration time shows a trend of gradually decreasing and then increasing. When the amount added is 0.6g, too many bubbles are generated, which coat the effervescent tablet and affect the disintegration of the effervescent tablet, thus prolonging the disintegration time. Therefore, when the amount of disintegrant added is 0.5g, the effervescent tablets of Phyllanthus urinaria extract have the best taste and the shortest disintegration time.

[0058] 6. Determination of the amount of sweetener sucralose added

[0059] Citric acid and sodium bicarbonate were selected as disintegrants in a ratio of 0.8:1. 10% of the *Phyllanthus urinaria* calyx extract powder was added. PEG6000 was added as a lubricant at 10%, polyvinylpyrrolidone as a binder at 6%, and mannitol as a filler, with the addition amount brought to 100%. The amount of sweetener significantly affects the taste and flavor of the effervescent tablets. Excessive sweetener dosage results in an overly sweet taste, while insufficient sweetener dosage fails to mask the bitterness of the total *Phyllanthus urinaria* extract, affecting the flavor. Single-factor experiments were conducted with additive dosages of 1%, 2%, 3%, 4%, and 5% to investigate the optimal ratio. The results are shown in Table 3 below.

[0060] Table 3. Effect of sweetener addition amount on sensory scores

[0061]

[0062] As shown in the table, a small amount of sweetener results in a bitter taste, while an excessive amount makes the solution overly sweet, masking the flavor of the total extract of Physalis alkekengi. Therefore, the recommended addition amount of sucralose is 4% of the total tablet weight.

[0063] 7. Determination of the amount of polyvinylpyrrolidone (PVP) added as an adhesive:

[0064] The binder for effervescent tablets is polyvinylpyrrolidone (PVP). Citric acid and sodium bicarbonate are selected as disintegrants in a ratio of 0.8:1. 10% total extract powder of *Physalis alkekengi* is added, along with PEG6000 as a lubricant at 10%. Mannitol is added to bring the total to 100%. The amount of binder affects tablet formation. Single-factor experiments were conducted with binder addition amounts of 2%, 4%, 6%, 8%, and 10% to investigate the effect of the binder ratio on the quality of effervescent tablets. The results are shown in Table 4. The amount of binder affects tablet formation, exhibiting a phenomenon where lower amounts result in poor tablet formation, while higher amounts lead to sticking and disintegration. At a 6% addition amount, the *Physalis alkekengi* total extract effervescent tablets showed the highest tableting success rate and a shorter disintegration time of 166 seconds. Therefore, the optimal addition amount of PPVP is 6% of the total tablet mass.

[0065] Table 4. Effect of binder dosage on disintegration time and tableting.

[0066]

[0067] 8. Determination of the amount of lubricant PEG6000 added:

[0068] The lubricant for the effervescent tablets was PEG6000, which was ground and passed through a 100-mesh sieve. The effervescent agent ratio was 0.8:1, with an effervescent agent content of 50% by mass. The content of *Phyllanthus urinaria* calyx extract powder was 10%, the binder was polyvinylpyrrolidone (PVP) at 6%, and the filler was mannitol, which was added to bring the total to 100%. The effects of PEG6000 additions of 5%, 7.5%, 10%, 12.5%, and 15% on the quality of the effervescent tablets were investigated, using the clarity of the disintegrated solution and tableting effect as standards. As shown in Table 5, when the addition amount was less than 10%, the solution was clear and transparent, but tableting exhibited sticking and tackiness. When the addition amount was greater than 10%, the solution gradually became turbid after disintegration. When the addition ratio was greater than 12.5%, the tablets showed a loose and difficult-to-form-shape tendency during formulation. Therefore, the formulation works best when the amount of PEG6000 added is 10%, and the solution is clear at the same time.

[0069] Table 5. Effects of PEG6000 dosage on solution clarity and tableting effect

[0070]

[0071]

[0072] 9. Optimization of the preparation process of effervescent tablets made from the calyx extract of *Phyllanthus urinaria*

[0073] (1) Response surface methodology

[0074] Based on the single-factor experiments, the following experimental designs were selected: disintegrant addition amounts of 40%, 50%, and 60%; disintegrant ratios of 0.6:1, 0.8:1, and 1.0:1; and binder addition amounts of 4%, 6%, and 8%. Design Expert 11 software was used, and the Box-Behnken design was employed for response surface methodology optimization. The evaluation indicators were disintegration time and sensory score. The response surface experimental factors and levels are shown in Table 6. The experimental results are shown in Table 7.

[0075] Table 6. Response Surface Experiment Factor Levels

[0076]

[0077] Table 7. Experimental Design and Results of Response Surface Optimization

[0078]

[0079]

[0080] (1) Disintegration time analysis: Through Box-Behnken design and data analysis, the multivariate nonlinear regression model equation for disintegration time Y1 and A (total disintegrant), B (disintegrant ratio), and C (adhesive dosage) is obtained as follows: Y1=152.20+0.25A+0.25B-1.25C-1.25AB+1.25AC+0.25BC+15.77A 2 +19.27B 2 +10.28C 2 Table 8 shows the results of the analysis of variance. The p-value of the model is 0.0009, which is less than 0.05, indicating that the model is statistically significant. The p-value of the lack-of-fit term is greater than 0.05 (P = 0.6227), indicating that the lack-of-fit term is not significant, suggesting that the model fits the experiment well. The quadratic coefficient A... 2 B 2 and C 2 All parameters showed a significant impact (P < 0.05), with a coefficient of variation (CV%) of 2.90, indicating that the higher the accuracy of the experiment, the smaller the influence of out-of-model factors on the response value. This model can be used to predict actual experimental results. The correlation coefficient R of the model is... 2 = 0.9508, Corrected coefficient of determination R 2 adj=0.8874. The closer these two values ​​are to 1, the higher the fit between the model's true value and the predicted value, and the more accurately the evaluation index can be predicted.

[0081] Table 8. ANOVA analysis of the disintegration time-limited regression model.

[0082]

[0083] Different conclusions can be drawn from the shape of contour lines. When the contour lines are circular, it indicates that the interaction between the factors is insignificant, while when the contour lines are elliptical, it indicates that the interaction between the two factors is significant. Figure 8 The effects of three factors—A (total disintegrant), B (disintegrant ratio), and C (binder dosage)—on the disintegration time of effervescent tablets are clearly visible. The p-values ​​for AB, AC, and BC are 0.6341, 0.9235, and 0.0078, respectively, indicating that the interaction between BC has the most significant effect on the disintegration time of effervescent tablets, followed by the interaction between AB and AC. The effects of A², B², and C² on the disintegration time are extremely significant (P < 0.01).

[0084] (2) Sensory evaluation analysis: Data analysis using a Box-Behnken design yielded the following multivariate nonlinear regression model equation for sensory score Y2 and A (total disintegrant), B (disintegrant ratio), and C (adhesive dosage): Y2 = 80.80 - 0.37A + 2.13B + 0.000C - 1.25AB - 2.00AC + 4.00BC - 9.53A 2 -10.03B 2 -9.27C 2 Table 9 shows the results of the analysis of variance. The p-value for the model is less than 0.0001, indicating that the model is statistically significant. The p-value for the lack-of-fit term is greater than 0.05 (P = 0.4753), indicating that the lack-of-fit term is not significant, suggesting that the model fits the experiment well. The quadratic coefficient A... 2 B 2 and C 2 The model had a significant impact on the sensory scores of effervescent tablets (P < 0.05), with a coefficient of variation (CV%) of 3.23. This indicates that the higher the accuracy of the experiment, the smaller the influence of out-of-model factors on the response value, and also suggests that the model can be used to predict actual experimental results. The correlation coefficient R of the model is [missing value]. 2 =0.9774, Corrected coefficient of determination R 2 adj =0.9483. The closer these two values ​​are to 1, the higher the fit between the model's true value and the predicted value, and the more accurately the evaluation index can be predicted.

[0085] Table 9. ANOVA analysis of the sensory rating regression model.

[0086]

[0087]

[0088] Based on the shape of the contour lines, it can be concluded that when the contour lines are circular, the interaction between the two factors is not significant, while when the contour lines are elliptical, the interaction between the two factors is significant. Figure 9 This indicates the influence of three factors—A (total disintegrant), B (disintegrant ratio), and C (binder amount)—on the sensory score of effervescent tablets. The interaction term BC and the quadratic term A are also discussed. 2 B 2 C 2 The p-value was less than 0.05, indicating that the interaction term between the disintegrant ratio and the amount of binder, as well as the quadratic term, had a significant impact on the sensory evaluation of effervescent tablets.

[0089] Based on Box-Behnken design analysis, the optimal preparation process for effervescent tablets containing *Phyllostachys edulis* extract was predicted to be 49.83% total acid-base content, 0.81:1 acid-base ratio, 6.06% binder, with a disintegration time of 152.21s and a sensory score of 80.87. According to actual experimental conditions, the process was adjusted to 50% total acid-base content, 0.8:1 acid-base ratio, and 6% polyvinylpyrrolidone. The effervescent tablet formulation was determined as follows: 10% *Phyllostachys edulis* extract, 50% disintegrant, 0.8:1 acid-base ratio, 10% PEG6000, 4% sucralose, 6% polyvinylpyrrolidone, and filler to 100% of tablet weight. All components were ground separately, passed through a 100-mesh sieve, dried in a drying oven, mixed thoroughly, and then compressed into tablets. The results are shown in Table 10. The average disintegration time and sensory score were 158s and 78 points, respectively, which verifies that the model has high accuracy and good fit.

[0090] Table 10. Disintegration time and sensory score of the best process

[0091]

[0092] Example 3: Quality Evaluation of Physalis alkekengi Extract Effervescent Tablets

[0093] Effervescent tablets were prepared using the optimal formulation and process obtained above for quality evaluation.

[0094] 1. Measurement of tablet weight variation

[0095] Take 20 effervescent tablets containing the extract of *Phyllostachys edulis*, accurately weigh the total weight of the tablets, calculate the average weight, and then accurately weigh each individual tablet. Compare the weight of each tablet with the average weight. A weight difference of <5% is considered acceptable. As shown in Table 11, the average weight is 0.9923g, and the weight difference of all effervescent tablets is <5%, which meets the requirements of the Chinese Pharmacopoeia.

[0096] Table 11 Quality Differences of Tablets

[0097]

[0098]

[0099] 2. Determination of the disintegration time of effervescent tablets

[0100] The disintegration time was determined according to General Chapter 0921 of the 2025 edition of the Chinese Pharmacopoeia. One effervescent tablet was placed in 200 mL of a beaker containing 200 mL of randomly selected total extract of *Phyllanthus urinaria*. The disintegration time was recorded, and all disintegration times were <5 minutes. The results are shown in Table 21.

[0101] Table 12 Determination of disintegration time

[0102]

[0103] 3. pH measurement

[0104] Ten effervescent tablets containing total extract of *Phyllanthus urinaria* calyx were randomly selected and placed into 250ml beakers containing 200ml of distilled water. The pH was measured and recorded after the bubbles completely disappeared. The results showed that the pH value of the effervescent tablets containing *Phyllanthus urinaria* calyx extract was 5.30±0.02.

Claims

1. An effervescent tablet containing extract of *Phyllanthus urinaria* calyx, its preparation process and quality evaluation, characterized in that... By weight percentage, it consists of the following components: 7-12% extract of *Phyllanthus urinaria* calyx, excipients including 50% total acid and alkali (acid-base ratio 0.6:1-1.4:1), 5%-15% lubricant, 1%-5% sweetener, 2%-10% binder, and filler to 100%. Of the total acid and alkali, the acid source is citric acid, and the alkali source is sodium bicarbonate.

2. The effervescent tablet of *Phyllanthus urinaria* calyx extract according to claim 1, characterized in that: The preparation method of the extract of Phyllanthus urinaria calyx is as follows: the Phyllanthus urinaria calyx is dried, cut into pieces, and 70% ethanol is added to the Phyllanthus urinaria calyx at a material-to-liquid ratio of 1:

4. The mixture is refluxed at 80°C for 2 hours, filtered, and the process is repeated twice. The filtrates are combined, concentrated, and freeze-dried to obtain the extract of Phyllanthus urinaria calyx.

3. The effervescent tablet of *Phyllanthus urinaria* calyx extract according to claim 1, characterized in that: The acid source is citric acid, and the base source is sodium bicarbonate, with a mass ratio of citric acid to sodium bicarbonate of 0.8:

1.

4. The effervescent tablet of *Phyllanthus urinaria* calyx extract according to claim 1, characterized in that: The lubricant is polyethylene glycol 6000, with an optimal ratio of 10%.

5. The effervescent tablet of *Phyllanthus urinaria* calyx extract according to claim 1, characterized in that: The sweetener is sucralose, with an optimal ratio of 4%.

6. The effervescent tablet of *Phyllanthus urinaria* calyx extract according to claim 1, characterized in that: The adhesive is polyvinylpyrrolidone, with an optimal ratio of 6%.

7. The effervescent tablet of *Phyllanthus urinaria* calyx extract according to claim 1, characterized in that: The filler is mannitol.

8. The effervescent tablets of *Phyllanthus urinaria* calyx extract and its preparation method according to claim 1, characterized in that: Polyethylene glycol 6000 is mixed with sodium bicarbonate, passed through a 100-mesh sieve, and dried in a drying oven. Citric acid, Physalis alkekengi extract, polyvinylpyrrolidone, sucralose, and mannitol are mixed evenly, passed through a 100-mesh sieve, and dried in a drying oven. The two materials are then mixed evenly and compressed into tablets.

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