Ginseng ultrafine powder buccal fast-release film and preparation method and application thereof

Abstract

The present application provides a kind of ginseng superfine powder oral fast-release film and its preparation method and application, it is related to oral mucosa drug preparation process technical field.The oral fast-release film includes the following weight parts of components: ginseng superfine powder 20-40 parts, PVA (polyvinyl alcohol) 4-10 parts, PVP (polyvinylpyrrolidone) 8-15 parts, honey 10-20 parts, glycerol 10-20 parts and tween-80 4-8 parts, above-mentioned weight parts are with dry film quality metering.The oral fast-release film is obtained by optimizing the mass ratio of film forming agent polyvinyl alcohol and polyvinylpyrrolidone and the ternary plasticizing flavor system composed of honey, glycerol and tween, realizes more than 20% drug loading, has the characteristics of faster disintegration (2.5-3.1 min under the test conditions of example) and good mechanical properties, is expected to improve the dissolution and onset speed of ginsenoside, is suitable for children, the elderly and dysphagia population.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of oral mucosa drug delivery, in particular to a ginseng ultrafine powder oral fast-dissolving film and its preparation method and application. BACKGROUND

[0002] Oral fast-dissolving film (OFF) is a kind of oral mucosa absorption type fast-release preparation. The drug is loaded in the film, which rapidly disintegrates and is absorbed through the oral mucosa or gastrointestinal tract after being wetted by saliva. It can accelerate the onset of action, bypass the liver first-pass metabolism to some extent, and improve the efficiency of drug delivery. The 2020 edition of Chinese Pharmacopoeia defines film as "a film-shaped preparation prepared by processing drug and suitable film-forming material for oral or mucosal use". This dosage form is suitable for children, the elderly or bedridden patients who have difficulty swallowing, and can improve the compliance of drug taking. In ginseng preparations, ginseng ultrafine powder (GUP) has the following advantages: the specific surface area is significantly increased, which promotes the dissolution of effective ingredients; the volatile oil, polysaccharides, saponins and other complete ingredient spectrum of ginseng are retained, and the drug efficacy is closer to the whole medicinal material; it can be blended with a hydrophilic matrix to form a film, and theoretically it is expected to realize the rapid drug delivery of "one piece at a time". Ginseng ultrafine powder has a larger specific surface area and a more complete ingredient spectrum than traditional coarse powder or extract, but ginsenosides have a heavy bitter taste, and the direct consumption of powder will cause a rough particle feeling, resulting in a "sandiness" and mucosa irritation, which affects the compliance of patients. Moreover, the ultrafine powder usually needs to be taken by a medicine spoon, but the powder has poor flowability and high adhesion, which easily causes dosage deviation, making it difficult to ensure the accuracy of the dose and the stability of the therapeutic effect.

[0003] However, a series of technical bottlenecks are still faced when a high proportion (≥8% w / w) of ginseng ultrafine powder is directly loaded into a buccal instant film: (1) insufficient drug content or single component, such as Chinese invention patent application CN107157963A relates to a ginseng polysaccharide oral dissolving film and a preparation method thereof, but the above application only contains ginseng polysaccharide and does not contain ginsenosides, the component is relatively single compared with the whole powder, and the content of ginsenosides in ginseng whole powder is relatively high, and the effect is better; Chinese invention patent application CN104784235A discloses a preparation method of fresh ginseng freeze-dried oral instant preparation, the content of ginsenosides is less than 10%, which is difficult to meet the effective dose; (2) high powder loading film is easy to crack and delay disintegration, when the loading amount is increased to ≥8%, the tensile strength of the film is significantly decreased, and the disintegration time is prolonged to >5 min (from the literature "Effect of surfactants and drug load on physico-mechanical and dissolution properties of nanocrystalline tadalafil-loaded oral films". European Journal of Pharmaceutical Sciences, Volume 109, 15 November 2017, Pages 372-380).

[0004] Therefore, it is urgent to develop a kind of oral instant film and its preparation method which can still maintain excellent mechanical properties, rapid disintegration and uniformity of taste and dose under the condition of high loading of ginseng ultrafine powder. SUMMARY

[0005] In view of the deficiencies of the prior art, the purpose of the present application is to provide a ginseng ultrafine powder-containing buccal immediate-release film and a preparation method and application thereof, by optimizing the mass ratio of film-forming agent polyvinyl alcohol (PVA) and polyvinylpyrrolidone (PVP), and using a ternary plasticizing / flavoring / wetting system composed of honey, glycerol and Tween-80, a buccal immediate-release film with good mechanical properties and rapid disintegration under high loading conditions is prepared; under the same metering caliber (based on the mass of dry film), the prescription has reproducibility and stability.

[0006] The technical solution adopted by the present application to solve its technical problems is as follows:

[0007] The first aspect of the present application relates to a ginseng ultrafine powder-containing buccal immediate-release film, which is prepared from the following raw materials in parts by weight: ginseng ultrafine powder 20-40 parts, PVA (polyvinyl alcohol) 4-10 parts, PVP (polyvinylpyrrolidone) 8-15 parts, honey 10-20 parts, glycerol 10-20 parts, Tween-80 4-8 parts, the above parts by weight are based on the mass of dry film.

[0008] Preferably, the mass ratio of PVA to PVP is 1:1.2-2.

[0009] Further preferably, the mass ratio of PVA to PVP is 3:5.

[0010] Preferably, the total amount of PVA and PVP accounts for 25%-40% of the mass of the dry film.

[0011] Preferably, the glycerol and honey independently account for 10%-20% of the mass of the dry film.

[0012] Preferably, the particle size D90 of the ginseng ultra-fine powder is ≤50µm.

[0013] Preferably, the mass ratio of the ginseng ultra-fine powder in the dry film is ≥20%.

[0014] Further preferably, the mass ratio of the ginseng ultra-fine powder in the dry film is ≥30%.

[0015] Preferably, to improve the disintegration performance, the thickness of the dry film is 0.05-0.20mm; the 1mm or 500µm thick film used for prescription screening in the embodiments of the present specification is only used for process condition exploration.

[0016] The second aspect of the present application relates to a preparation method of the above-mentioned ginseng ultra-fine powder-containing buccal rapid-release film, which comprises the following steps:

[0017] (1) Dissolve the film-forming materials PVA and PVP in water by heating, and then add glycerol, honey and Tween-80 in sequence to obtain a mixed solution;

[0018] (2) Disperse the ginseng ultra-fine powder in the mixed solution, homogenize and vacuum degassing;

[0019] (3) Casting, drying, demolding and cutting, and the ginseng ultra-fine powder-containing buccal rapid-release film is obtained.

[0020] Preferably, the PVA and PVP in step (1) are soaked for 20-26h, and the heating temperature is 80-100℃.

[0021] Preferably, in step (3), the casting is performed at 45-55℃ for 45-60min, and the film thickness is 0.05-0.20mm in terms of the thickness of the dry film.

[0022] Further preferably, the thickness of the dry film of the ginseng ultra-fine powder-containing buccal rapid-release film is 0.08-0.12mm.

[0023] Preferably, the drying in step (3) is specifically: first stage, air-drying at 50-55℃ for 40-50min, second stage, vacuum-drying at 30-35℃, -0.08MPa for 60-90min, until the final moisture content is ≤5%.

[0024] The third aspect of the present application relates to the use of the above-mentioned buccal fast-release film containing ginseng ultra-fine powder or the buccal fast-release film containing ginseng ultra-fine powder prepared according to the above-mentioned preparation method in the preparation of a drug for oral mucosal administration.

[0025] The beneficial effects of the present application compared with the prior art include: the preferred mass ratio of the film-forming agent PVA (polyvinyl alcohol) to PVP (polyvinyl pyrrolidone) and the preferred ternary plasticizing and flavoring system composed of honey, glycerol, and Tween under high load conditions obtain better film-forming property and flexibility, the disintegration time is 2.5-3.1min under the test conditions of the examples (37℃, 50mL water, 60rpm), showing a faster disintegration trend; and it is expected to improve the dissolution and onset speed of ginsenosides, suitable for children, the elderly and people with swallowing disorders. BRIEF DESCRIPTION OF DRAWINGS

[0026] Figure 1 : Particle size distribution graph of ginseng ultra-fine powder in Example 1;

[0027] Figure 2 : Film appearance graph of the buccal fast-release film obtained in Example 4. DETAILED DESCRIPTION

[0028] The following describes the embodiments of the present application in detail: The present embodiments are implemented on the premise of the technical solutions of the present application, and detailed implementation methods and processes are given, but the protection scope of the present application is not limited to the following embodiments. The experimental methods not specified in the following embodiments are usually performed under conventional conditions.

[0029] Example 1: Preparation of ginseng ultra-fine powder

[0030] Select ginseng without deterioration, cut into blocks, crush in a pulverizer, pass through an 80-mesh sieve (178μm), and dry to a water content of less than 10%. To further refine the ginseng powder, use a ball mill to ultra-finely crush for 4-8h, separate the material from the grinding balls with a screen, pass through a 300-mesh sieve (48μm), and obtain ginseng ultra-fine powder, which is stored in a bag.

[0031] Measure the particle size distribution of the ginseng ultra-fine powder by an LS-POP (9) laser particle size analyzer under the conditions of a medium refractive index of 1.333, an obscuration rate of 10.96%, and a dispersion medium of purified water. The results are shown in Table 1 and Figure 1 .

[0032] Table 1: Particle size distribution table of ginseng ultra-fine powder

[0033]

[0034] By Figure 1 The results of Table 1 show that the particle size distribution of the sample is relatively concentrated, showing a single peak symmetry, and the particle size is mainly concentrated in the 5-30 μm range. At a particle size of 11.565 μm, the differential percentage content reaches 8.14%, which is the peak point of the distribution, corresponding to an accumulated content of 41.41%, indicating that this particle size segment is the main particle group; the particle size of 14.666 μm corresponds to a differential content of 6.92%, and the cumulative value reaches 48.33%, further indicating that the main distribution area is concentrated in the medium particle size segment; the cumulative content at a particle size of 29.907 μm is 78.40%, indicating that nearly 80% of the particles have a particle size of not more than 30 μm; D 10 , D 50 and D 90 (estimated value) are located near about 4 μm, 11-13 μm and 30-35 μm, respectively, showing that the sample particle size distribution range is moderate and the fineness is high; the portion with a particle size greater than 60.988 μm accounts for only 0.08%, indicating that there are very few large particle impurities and the distribution convergence is good; when the particle size exceeds 77.339 μm, the differential content is 0.00% and the cumulative distribution reaches 100.00%, indicating that the particle size determination is complete.

[0035] Example 2: Single film-forming material screening

[0036] From six common hydrophilic polymers including polyvinyl alcohol (PVA), polyvinylpyrrolidone (PVP), gelatin, chitosan, xanthan gum and gum arabic, the most suitable film-forming material for oral fast-dissolving film was screened. The focus of the investigation was placed on five indicators: film-forming integrity, drying and demolding convenience, flexibility, disintegration performance after soaking and appearance uniformity. To reduce operational bias, three batches of parallel samples were prepared for each material at a ratio of 2 g / 20 mL, and ginseng ultra-fine powder (GUP) was uniformly added, so that the mass ratio of ginseng ultra-fine powder to film-forming material was 1:1 (based on the dry film mass); the film was prepared on a clean glass substrate using the blade coating method for comparison.

[0037] (1) Experimental operation

[0038] Each film-forming material was first soaked in a specified medium to ensure swelling, then heated in a water bath at 80-95°C until completely dissolved; before dissolving, PVA and PVP were pre-soaked for 24h, gelatin could be directly heated and dissolved, chitosan was prepared as an acidic solution with 2% (w / w) acetic acid as the solvent, xanthan gum and gum arabic were cold-soaked for 12h before heating to eliminate agglomeration. After the viscosity of the solution was stable, pre-weighed ginseng ultra-fine powder was added and uniformly dispersed by high-speed homogenization (8000 rpm, 2 min), followed by vacuum degassing at -0.08 MPa for 3 min. While the flowability was optimal, it was thinly spread on a clean glass plate and uniformly coated on a clean glass plate (100 mm x 100 mm) using an adjustable doctor blade (wet film thickness 500 µm). All the films were dried to constant weight in an environment of 25 ± 2°C and relative humidity of 45 ± 5%, then peeled off as a whole. After drying, the dry film thickness was measured at 5 points on the film surface with a micrometer, and the average value was recorded (target 0.08-0.12 mm).

[0039] (2) Observation and evaluation

[0040] After drying, the smoothness, transparency and bubble / crack defects of the film surface were observed first; then the size of the external force required for demolding was recorded to judge the film strength and adhesion; the bending resistance times of the film under constant humidity conditions were measured to evaluate the flexibility; finally, a 1 cm x 1.3 cm segment was put into 50 mL of distilled water and shaken to observe the time required for complete disintegration. The three batches of data show that: the PVA film has the smoothest and most transparent surface, the demolding is smooth, the film can be bent 180° for 20 times without cracking, and it quickly disintegrates in water without sticking; the PVP film is transparent but brittle and curls after absorbing moisture; the gelatin film has shrinkage lines after drying and easily curls at room temperature; the chitosan film is opaque and has low fracture flexibility; xanthan gum and gum arabic only form brittle gel films, which have poor integrity and long disintegration time.

[0041] (3) Conclusion

[0042] Under the same ginseng ultra-fine powder load (50% of the dry film) and the same thickness, the PVA film showed: smooth and transparent film surface, peel force less than 0.5N, high elongation at break, shortest disintegration time and no sticking; the PVP film had good transparency but was brittle and curled after absorbing moisture; the gelatin film had shrinkage lines after drying and curled at room temperature; the chitosan film was opaque and had low elongation at break; xanthan gum and gum arabic only formed brittle gel films, which had poor integrity and long disintegration time. PVA performed best among the single materials, forming a film with good mechanical properties and short disintegration time under standard conditions without the addition of plasticizers, making it suitable as the main film-forming material for subsequent compounding and prescription optimization; the remaining materials each have limitations and can be used as auxiliary materials or compounded with PVA to improve specific properties, but should not be used as the main material alone. To ensure comparability, the above conclusions were obtained under uniform ginseng ultra-fine powder load, film thickness and test conditions.

[0043] Example 3: Composite film-forming material screening

[0044] Based on the single film-forming material screening results, polyvinyl alcohol (PVA) was used as the main body, and hydrophilic polymers such as polyvinylpyrrolidone (PVP) were compounded to investigate the effect of prescription composition on oral fast-dissolving films. Orthogonal design was used to optimize the three factors of plasticization (glycerol), flavoring (honey), and wetting / emulsification (Tween-80) to obtain the optimal prescription. Unless otherwise specified, "mass parts" and "percentage content" are based on the mass of dry film, the environmental conditions are 25 ± 2°C and 45 ± 5% RH, the ratio of ginseng ultra-fine powder to total polymer is 1:1 (dry film basis), and the dry film thickness is controlled for comparison.

[0045] (1) Preparation of film-forming solution

[0046] For each test group, 2.00 g of total polymer was prepared in 30 mL of pure water or 2% acetic acid solution (for chitosan). PVA / PVP was pre-soaked for 24 h and then completely dissolved in a 90°C water bath; gelatin was added directly and heated; chitosan was dissolved in an acidic medium. After the solution viscosity stabilized, ginseng ultra-fine powder (GUP), glycerol, honey, and Tween-80 were added in sequence, and the slurry was magnetically stirred for 5 min to ensure homogeneity. The hot slurry (55-60°C) was evenly coated onto a clean glass plate (20 cm x 20 cm), and the film was dried to constant weight at 25°C and 45% RH before being peeled off.

[0047] (2) Evaluation indicators and detection methods

[0048] Film-forming time: from the completion of coating to the film surface no longer adhering to the glass rod, accurate to 0.1 min.

[0049] Disintegration time: cut 1.0 cm x 1.3 cm samples (n = 3), place in 50 mL pure water at 37°C and shake (60 rpm), record the time when the film completely disintegrates and no visible fragments are present.

[0050] Flexibility: according to ASTM D882-18, cut 5 mm x 50 mm test strips (n = 5), stretch to break at 50 mm / min, and record the elongation length.

[0051] Appearance score: based on film uniformity, color consistency, and bubble defects, use a 10-point scale (total of 10 points, uniformity 4 points, color 3 points, and bubbles 3 points).

[0052] (3) Design scheme

[0053] Compound feasibility screening: investigate the effect of PVA and PVP, gelatin, chitosan, and their ternary and quaternary systems on film properties.

[0054] PVA and PVP mass ratio gradient experiment: set 3:1, 5:3, 1:1, 3:5, 1:3 five grades, to clear the best mass ratio of binary system.

[0055] Single factor investigation: on the basis of fixing PVA: PVP = 3:5, ginseng ultra-fine powder (GUP) 2g, water 30mL, respectively adjust the content of glycerol, honey, Tween-80 (glycerol 10-20%, honey 10-20%, Tween-80 1.4-1.6%, mass fraction, the same below, wherein the mass fraction of glycerol and honey does not include the weight of water in the system, and the mass fraction of Tween-80 includes the weight of water in the system).

[0056] (4) Compound results

[0057] PVA / PVP binary system film forming is complete, and can be peeled off within 25±2min; PVA / gelatin and PVA / chitosan are eliminated respectively due to dry shrinkage and opacity; ternary and quaternary systems are inferior to binary systems in appearance and toughness.

[0058] The PVA: PVP = 3:5 group has the shortest film forming time (23.8±1.1min), the fastest disintegration (2.7±0.3min), the highest flexibility (150%) and the highest appearance score (9.2±0.2 points). When PVA is excessive (PVA / PVP mass ratio is 3:1), the film body is brittle and cracked; when PVP is excessive (PVA / PVP mass ratio is 1:3), the film appears sticky and stringing.

[0059] (5) Single factor investigation results

[0060] ① Investigation of glycerol dosage: glycerol addition amounts are 0.67g (10%), 1.06g (15%), 1.5g (20%), and 2.0g film forming material (PVA: PVP = 3:5), 2.0g ginseng ultra-fine powder (GUP), 0.5g Tween-80, 1.5g honey, and 30mL water are used to prepare films with different glycerol addition amounts. Preparation method: dissolve the film forming materials PVA and PVP in 90℃ water, cool to 50℃, after complete dissolution, add glycerol, honey and Tween-80 in sequence to obtain a mixed solution; uniformly disperse ginseng ultra-fine powder in the mixed solution, homogenize and vacuum degassing; coat and shape to a wet film thickness of 1.0mm, first dry at 50℃ for 45min, then vacuum dry at 30℃ and -0.08MPa for 60min until the final water content is ≤5%, vacuum dry, demould, and cut.

[0061] The elongation rates of the three groups of ginseng ultra-fine powder (GUP) containing oral fast-release films with different glycerol contents are 120%, 130% and 135% respectively. The film forming property, solubility, flexibility and appearance of the films are shown in the following table.

[0062] Table 2: Glycerin content investigation results table

[0063]

[0064] From the data in Table 2, it can be seen that the glycerin content has a significant effect on the film forming time, and the flexibility also changes with different glycerin contents. The properties of the 10% and 15% groups are not much different, the 15% group has relatively good flexibility, and when the content is 20%, the film forming time of the film is prolonged, and the produced film is slightly sticky. Considering the glycerin content comprehensively, 15% is the best.

[0065] ②Honey dosage investigation

[0066] The honey addition amounts were 0.67 g (10%), 1.06 g (15%), and 1.5 g (20%), respectively, and were mixed with 2.0 g of film forming material (PVA:PVP=3:5), 2.0 g of ginseng ultra-fine powder (GUP), 0.5 g of Tween-80, 1.5 g of glycerin, and 30 mL of water to prepare film preparations with different honey addition amounts. The preparation method was as follows: the film forming materials PVA and PVP were dissolved in 90°C water, cooled to 50°C, and after complete dissolution, glycerin, honey, and Tween-80 were added in sequence to obtain a mixed solution; the ginseng ultra-fine powder was dispersed in the mixed solution, homogenized, and vacuum degassed; the wet film was formed to a thickness of 1 mm, first dried at 50°C for 45 min, then vacuum dried at 30°C and -0.08 MPa for 60 min until the final water content was ≤5%, the film was removed, cut, and obtained.

[0067] The appearance scores of the film preparations with 10%, 15%, and 20% honey were 7.6, 9.0, and 8.4, respectively, and the drying rate decreased by 22% at 20%. The film forming properties, solubility, flexibility, and appearance of the film were investigated, and the results are shown in Table 3.

[0068] Table 3: Honey content investigation results table

[0069]

[0070] As shown in the above table, honey mainly affects the solubility and film forming properties of the film preparation. The 20% group has a long film forming time, a sticky texture, and a poor comprehensive evaluation. The 10% and 15% groups have similar film forming time, dissolution time, and appearance flexibility, and considering the good taste of honey, the 15% group is finally selected as the best.

[0071] ③Tween-80 dosage investigation

[0072] Tween-80 addition amount of 0.53 g (1.4%), 0.56 g (1.5%), 0.6 g (1.6%) respectively, 2.0 g film forming material (PVA: PVP = 3:5), 2.0 g ginseng ultra-fine powder, 1.5 g honey, 1.5 g glycerol, water 30 mL were prepared into film agent. According to the following method: the film forming material PVA, PVP was dissolved in 90℃ water, cooled to 50℃, after complete dissolution, glycerol, honey, Tween-80 was added in turn, the mixed solution was obtained; the ginseng ultra-fine powder was dispersed in the mixed solution, homogenized and vacuum degassing; the wet film thickness was 1 mm, first dried at 50℃ for 45 min, then vacuum dried at 30℃, -0.08 MPa for 60 min, until the final moisture content ≤5%, vacuum drying, demolding, cutting, and the film was obtained.

[0073] Results: The disintegration time decreased from 3.4 ± 0.2 min at 1.4% to 2.6 ± 0.3 min at 1.6%, and the surface bubble rate of 1.6% group was the lowest (<2 / cm²). The results of film forming, solubility, flexibility and appearance of the film are shown in Table 4.

[0074] Table 4: Results of Tween-80 content investigation

[0075]

[0076] The results of Table 4 show that Tween-80 mainly affects the dissolution time of the film, and the dissolution time is 1.6% <1.5% <1.4%. Considering the content of 1.6% group, it is the best.

[0077] In summary, the optimal scheme in the single factor investigation results is Tween-80 1.6%, honey 15%, and glycerol 15%. Based on this, further orthogonal test is designed to optimize the preparation process.

[0078] (6) Orthogonal test optimization

[0079] Orthogonal optimization: L9(3 3 ) table was used, and glycerol (A), honey (B), and Tween-80 (C) were combined at three levels, as shown in Table 5. The optimal formula was screened with the target function S = film forming (10) + disintegration (10) + flexibility (10) + appearance (10).

[0080] Table 5: Orthogonal test design table

[0081]

[0082] L9(3 3 ) orthogonal table was used, and the results are shown in Table 6. The variance analysis of orthogonal test results is shown in Table 7.

[0083] Table 6: Orthogonal test results table

[0084]

[0085] Table 7: Analysis of variance of orthogonal test results

[0086]

[0087] According to the results of Table 6 and Table 7, the combination A2B2C3 (glycerol 15%, honey 15%, Tween-80 high level) obtained the highest comprehensive score (36 points) under the conditions of this test. The range analysis showed that A (glycerol) had the greatest impact, followed by C (Tween-80), and B (honey) was the smallest. According to the single factor ANOVA of Taguchi combined error method (α = 0.05), the main effect of A and C was significant, and B was not significant. Therefore, A2B2C3 is recommended as the preferred combination for prescription optimization. The suboptimal combination is A2B1C2 (33 points)

[0088] Example 4: Verification of preferred prescription

[0089] A ginseng ultra-fine powder buccal fast-release film, the preparation raw materials are: ginseng ultra-fine powder 3.0 g, PVA 0.75 g, PVP 1.25 g, glycerol 1.2 g, honey 1.2 g, Tween-80 0.6 g, and pure water 30 mL.

[0090] The preparation method is: (1) dissolve the film-forming materials PVA and PVP in 90°C water, cool to 50°C, after complete dissolution, add glycerol, honey, and Tween-80 in sequence to obtain a mixed solution; (2) disperse the ginseng ultra-fine powder in the mixed solution, homogenize at high speed for 8000 rpm x 2 min, and vacuum degassing at -0.08 MPa for 3 min; (3) spread and form to a dry film thickness of 0.1 mm, first dry at 50°C for 45 min, then vacuum dry at 30°C and -0.08 MPa for 60 min until the final moisture content is ≤5%, remove the film, cut, and obtain the film. The appearance of the obtained film is shown in Figure 2 .

[0091] After three repeated verifications, the film performance was determined according to the evaluation index and detection method of Example 3. The results are shown in Table 8.

[0092] Table 8: Performance test results of films after three repeated verifications

[0093]

[0094] After three repeated verifications, the average film forming time was 24.1 ± 0.9 min, the disintegration time was 2.8 ± 0.3 min, the elongation rate was 27 ± 1 mm, and the appearance score was 9.3 ± 0.1. All quality indicators were better than the design threshold, indicating that the optimized process parameters had good stability and reliability.

[0095] Comparative Example 1:

[0096] A ginseng ultrafine powder buccal immediate-release film, prepared from the following raw materials: ginseng ultrafine powder 3.0 g, PVA 0.75 g, PVP 1.25 g, honey 1.20 g, Tween-80 0.60 g, and pure water 30 mL.

[0097] Preparation method:

[0098] (1) Dissolve the film-forming materials PVA and PVP in 90°C water, and cool to 50°C;

[0099] (2) After complete dissolution, add honey and Tween-80 in sequence to obtain a mixed solution;

[0100] (3) Disperse the ginseng ultrafine powder in the mixed solution, and homogenize at a high speed of 8000 rpm for 2 min, and deaerate at -0.08 MPa for 3 min;

[0101] (4) Form by scraping, and set the wet film thickness to make the dry film thickness 0.10 ± 0.02 mm;

[0102] (5) Dry: first dry at 50°C for 45 min, then vacuum dry at 30°C and -0.08 MPa for 60 min until the final moisture content is ≤5%, remove the film, cut, and store in a sealed container at 25 ± 2°C and 45 ± 5% RH.

[0103] Note: This comparative example only removes glycerol, and the rest of the proportions are consistent with the ternary prescription, to ensure single-variable comparison.

[0104] Comparative Example 2:

[0105] A ginseng ultrafine powder buccal immediate-release film, prepared from the following raw materials: ginseng ultrafine powder 3.0 g, PVA 0.75 g, PVP 1.25 g, glycerol 1.20 g, Tween-80 0.60 g, and pure water 30 mL.

[0106] Preparation method:

[0107] (1) Dissolve PVA and PVP in 90°C water, and cool to 50°C;

[0108] (2) After complete dissolution, add glycerol and Tween-80 in sequence to obtain a mixed solution;

[0109] (3) Disperse the ginseng ultrafine powder in the mixed solution, and homogenize at a high speed of 8000 rpm for 2 min, and deaerate at -0.08 MPa for 3 min;

[0110] (4) The coating is dried to a dry film thickness of 0.10 ± 0.02 mm by first blowing at 50°C for 45 min, and then vacuum drying at 30°C and -0.08 MPa for 60 min until the final moisture content is ≤5%, and then stripping and cutting.

[0111] (5) Drying is the same as in Comparative Example 1.

[0112] Note: Only the honey solids are removed, and the rest of the proportions are the same as in the ternary prescription.

[0113] Comparative Example 3:

[0114] A ginseng ultra-fine powder buccal fast-release film is prepared using the following raw materials: ginseng ultra-fine powder 3.0 g, PVA 0.75 g, PVP 1.25 g, glycerol 1.20 g, honey 1.20 g, and pure water 30 mL.

[0115] Preparation method:

[0116] (1) PVA and PVP are dissolved in water at 90°C, and then cooled to 50°C;

[0117] (2) After complete dissolution, glycerol and honey are added in sequence to obtain a mixed solution;

[0118] (3) The ginseng ultra-fine powder is dispersed in the mixed solution, homogenized at 8000 rpm for 2 min, and defoamed at -0.08 MPa for 3 min;

[0119] (4) The coating is dried to a dry film thickness of 0.10 ± 0.02 mm by first blowing at 50°C for 45 min, and then vacuum drying at 30°C and -0.08 MPa for 60 min until the final moisture content is ≤5%, and then stripping and cutting.

[0120] Note: Only Tween-80 is removed, and the rest of the proportions are the same as in the ternary prescription.

[0121] The film-forming performance data of Comparative Examples 1-3 are determined according to the evaluation indexes and detection methods of Example 3. The results are shown in Table 9.

[0122] Table 9: Film-forming performance of Comparative Examples 1-3

[0123]

[0124] Glycerin is the most effective internal plasticizer, and the absence of glycerin in Comparative Example 1 results in decreased film body toughness and easy brittle fracture. The high sugar content and viscosity of honey result in poor flow leveling during casting, slow drying, and poor taste and color in Comparative Example 2. The absence of honey in Comparative Example 2 results in slightly poor uniformity and a general drying speed. The absence of Tween-80 in Comparative Example 3 results in a significant increase in disintegration time (emulsification + wetting). The performance of the film prepared by the binary system is not as good as that prepared by the ternary system.

[0125] Finally, it should be noted that the above content is only used to illustrate the technical solutions of the present application, and is not a limitation on the protection scope of the present application. Simple modifications or equivalent replacements of the technical solutions of the present application made by those skilled in the art do not deviate from the essence and scope of the technical solutions of the present application.

Claims

1. A buccal fast release film containing ginseng ultrafine powder, characterized in that, The oral quick-release film is prepared from the following raw materials in parts by weight: 20-40 parts of ginseng ultrafine powder, 4-10 parts of PVA, 8-15 parts of PVP, 10-20 parts of honey, 10-20 parts of glycerol, and 10-20 parts of Tween 80 4-8 parts, all based on the mass of the dry film; wherein the mass ratio of the PVA to the PVP is 1:1.2-2; the total amount of the PVA and the PVP accounts for 25%-40% of the mass of the dry film; and the proportions of the glycerol and the honey, independently, are selected from 10%-20% of the mass of the dry film.

2. The ginseng-containing ultrafine powder-containing oral fast-release film according to claim 1, characterized by, The ginseng ultrafine powder has a particle size D90 of ≤50 µm, and a mass ratio in the dry film of ≥30%.

3. A method for preparing the ginseng ultrafine powder-containing oral fast-release film according to any one of claims 1-2, characterized in that, The preparation method comprises the following steps: (1) PVA, PVP were dissolved in water by heating, glycerol, honey, Tween 80, to obtain a mixture; (2) dispersing the ginseng ultrafine powder in the mixed solution, homogenizing and vacuum defoaming; (3) casting, drying, demolding, cutting, to obtain the ginseng ultrafine powder-containing buccal rapid-release film.

4. The production method according to claim 3, characterized by, In the step (1), the PVA and PVP are soaked for 20-26 h, and the heating temperature is 80-100 ℃.

5. The preparation method according to claim 3, characterized in that, In the step (3), the casting is performed at 45-55 ℃ for 45-60 min, and the thickness of the ginseng ultrafine powder-containing buccal rapid-release film is 0.05-0.20 mm in terms of the thickness of the dry film.

6. The preparation method according to claim 3, characterized in that, In the step (3), the drying is specifically as follows: first-stage air-drying at 50-55 ℃ for 40-50 min, and second-stage vacuum drying at 30-35 ℃ and -0.08 MPa for 60-90 min, until the final water content is ≤5%.

7. Use of the ginseng ultrafine powder-containing buccal rapid-release film according to any one of claims 1-2 or prepared by the preparation method according to any one of claims 3-6 in the preparation of a drug for oral mucosal administration.

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