Oral buccal tablet and preparation method thereof

Abstract

The invention discloses an oral lozenge in the field of oral pharmaceutical preparations, which is prepared from the following raw materials in parts by weight: 10-30 parts of snow pear, 5-15 parts of honeysuckle, 5-15 parts of orange peel, 5-15 parts of kudzuvine root, 5-15 parts of loquat, 5-15 parts of momordica grosvenori, 3-10 parts of liquorice, 3-10 parts of boat-fruited sterculia seed, 3-10 parts of almond, 3-10 parts of mint, 1-5 parts of galangal, 1-5 parts of lily, mannitol and peach gum. According to the oral lozenge disclosed by the invention, the quick-release pellets and the sustained-release pellets are scientifically proportioned, and mannitol in the quick-release pellets is used as a carrier, so that the oral lozenge can quickly release components with cooling and throat-moistening effects within 5-10 minutes after being taken, and acute uncomfortable symptoms such as throat dry itching and pain can be quickly relieved; and the sustained-release pellets are wrapped by peach gum and can continuously release components with antibacterial, anti-inflammatory, cough-relieving and sputum-reducing effects within 2-5 hours, so that the organic combination of quick action and long-acting treatment is realized.

Description

Technical Field

[0001] The present invention relates to the technical field of oral medicine preparations, and in particular to an oral lozenge and a preparation method thereof. Background Art

[0002] Oral lozenges are pharmaceutical preparations that are absorbed through the oral mucosa or act locally, primarily used to relieve oral and pharyngeal discomfort, provide antibacterial and anti-inflammatory treatments, or assist in the treatment of localized diseases. As a commonly used preparation for pharyngeal ailments (such as mild coughs, pharyngitis, and dry throat), oral lozenges require a balance between speed of onset and duration of efficacy. Current mainstream lozenge technologies can be divided into two categories: rapidly disintegrating lozenges and sustained-release lozenges. Rapidly disintegrating lozenges, including freeze-dried instant dissolving tablets and oral instant dissolving films, utilize superdisintegrants or freeze-drying processes to shorten disintegration times to 30 seconds to 5 minutes, enabling rapid drug release to alleviate acute symptoms such as oral ulcers. However, these lozenges also have significant drawbacks. Due to their "burst" release pattern, the initial peak drug concentration is too high, easily irritating the oral and pharyngeal mucosa and causing discomfort. The drug concentration then rapidly decays, requiring repeated dosing every 0.5-2 hours. This leads to poor patient compliance. For example, during an acute cough, Xiguaseng throat lozenges require repeated dosing every 10-20 minutes to relieve discomfort. Sustained-release lozenges, including multilayer tablets and coated pellets, utilize polymer coatings or multilayer structures to extend the disintegration time to 10-30 minutes, achieving slow drug release. However, these tablets also have significant drawbacks: delayed onset of action, which can lead to delayed relief of acute throat discomfort. Furthermore, sustained release is typically achieved by adding excipients (ethyl cellulose), which results in high excipient dosages, potentially increasing mucosal adhesion and affecting saliva secretion and normal swallowing.

[0003] In the care of throat diseases, such as mild coughs caused by colds or chronic pharyngitis, patients need lozenges to quickly relieve throat itching and suppress cough reflexes, while avoiding repeated irritation caused by fluctuations in drug concentrations. Therefore, it is particularly important to balance rapid symptom relief and continuous control of inflammation.

[0004] In recent years, some studies have attempted to optimize drug release patterns through composite technologies, such as bilayer tablet technology. Bilayer tablets are compressed twice, with each layer containing different drugs or excipients. This can avoid compatibility changes between different drugs in compound preparations or achieve different drug release characteristics (such as the effect of sustained-release / immediate-release combinations). However, compared with ordinary tablets, bilayer tablets are complex to produce, with low production efficiency and high costs. In addition, the tablets are large and difficult for children to swallow. There are also studies on microencapsulation technology, which first prepares the drug into sustained-release microcapsules and then compresses them into tablets. However, the microcapsules are prone to rupture during the compression process, resulting in unstable sustained-release effects. Summary of the Invention

[0005] The present invention addresses the deficiencies of the prior art and provides an oral lozenge with a dynamic balance between disintegration speed and drug release mode.

[0006] One of the purposes of the present invention is to provide an oral lozenge, which is prepared from the following raw materials in parts by weight: 10-30 parts of snow pear, 5-15 parts of honeysuckle, 5-15 parts of orange peel, 5-15 parts of kudzu root, 5-15 parts of loquat, 5-15 parts of momordica grosvenori, 3-10 parts of liquorice, 3-10 parts of pistachio, 3-10 parts of almond, 3-10 parts of mint, 1-5 parts of ginger and 1-5 parts of lily; and further comprises a certain proportion of mannitol capable of regulating sweetness and disintegration speed, and a certain proportion of peach gum capable of sustained release speed.

[0007] Preferably, the oral lozenges of the present invention are made of the following raw materials in parts by weight: 20 parts of snow pear, 10 parts of honeysuckle, 5 parts of orange peel, 10 parts of kudzu root, 10 parts of loquat, 15 parts of momordica grosvenori, 5 parts of licorice, 5 parts of sterculia lychnophora, 3 parts of almond, 5 parts of mint, 2 parts of ginger and 3 parts of lily.

[0008] A second object of the present invention is to provide a method for preparing oral lozenges, comprising mixing snow pear, honeysuckle, tangerine peel, kudzu root, loquat, momordica grosvenori, licorice, puffed sea water, almond, ginger, mint, and lily in proportion, boiling with water, concentrating, and granulating to obtain Chinese medicine granules; mixing part of the boiled Chinese medicine granules with mannitol to obtain quick-release micropellets, and wrapping the other part of the boiled Chinese medicine granules with peach gum to obtain sustained-release micropellets; and mixing the quick-release micropellets and the sustained-release micropellets in a ratio of 1:1 to 1:5, and pressing the mixture into tablets to obtain oral lozenges.

[0009] Preferably, the mixing ratio of the quick-release pellets and the sustained-release pellets is 1:3 to 1:4.

[0010] Preferably, in the step of adding water and boiling, the amount of water added is 5 to 10 times the total weight of the raw materials, the boiling temperature is 80 to 100° C., and the boiling time is 2 to 10 hours.

[0011] Preferably, the granulation method is spray drying or freeze drying. Spray drying is preferred. If it is necessary to add some antibacterial and anti-inflammatory drugs to the lozenges, freeze drying can also be selected according to the heat sensitivity of the drugs.

[0012] Furthermore, the particle size of the granulated Chinese medicine particles is 100 to 200 meshes, preferably 150 to 200 meshes.

[0013] Furthermore, the amount of mannitol used is 10-30% of the weight of the Chinese medicine granules. The total amount of Chinese medicine granules here refers to the weight of the part of Chinese medicine granules mixed with mannitol. The amount of mannitol can be selected according to the sweetness and disintegration speed of the medicine.

[0014] Furthermore, the amount of peach gum used is 5-15% of the weight of the Chinese medicine granules. The total amount of Chinese medicine granules herein refers to the weight of the part of Chinese medicine granules mixed with peach gum.

[0015] Working principle and beneficial effects of the present invention:

[0016] The formula of the present invention adopts a variety of natural raw materials with medicinal and edible properties, such as snow pear, honeysuckle, and licorice. Compared with lozenges containing chemically synthesized ingredients, it greatly reduces the risk of toxic side effects and allergies, and is especially suitable for long-term use by special groups such as children and the elderly. The addition of ginger can harmonize the medicinal properties of the cold and cool drugs in the formula, reduce irritation to the spleen and stomach, and improve product safety and applicability.

[0017] The present invention uses a scientific ratio of rapid-release micropills and sustained-release micropills. Mannitol is used as a carrier in the rapid-release micropills, so that the oral lozenges can quickly release ingredients such as snow pear and mint with cooling and soothing throat effects within 5 to 10 minutes after oral administration, quickly relieving acute discomfort symptoms such as dry, itchy and painful throats. The sustained-release micropills are coated with peach gum and can continuously release ingredients such as licorice, honeysuckle and puffed sea with antibacterial and anti-inflammatory, cough-relieving and expectorant effects within 2 to 5 hours, continuously acting on the throat area, avoiding the problems of excessively high drug concentration in the early stage of traditional lozenges that irritates the mucosa and insufficient concentration in the later stage that causes therapeutic effect to decline, thereby achieving an organic combination of rapid onset and long-term treatment.

[0018] In addition, the present invention adopts micro-pill filling and peach gum wrapping technology to effectively protect the heat-sensitive components and volatile components in the raw materials, such as chlorogenic acid in honeysuckle and menthol in mint, to prevent them from losing their effectiveness due to factors such as high temperature during the preparation process; at the same time, peach gum, as a natural polymer material, can form a wrapping layer that can effectively block external moisture and oxygen, improve the stability of the lozenges, and extend the shelf life.

[0019] By adjusting the mixing ratio of immediate-release and sustained-release pellets, as well as the weight proportions of each raw material, the present invention can flexibly customize products for different symptoms, populations, and taste requirements. For patients with significant cough symptoms, the proportions of loquat and almond can be appropriately increased, and the proportion of sustained-release pellets can be increased to enhance the sustained effect of cough and asthma relief. For patients with dry throat pain, the content of mint and pistachio can be increased, and the proportion of immediate-release pellets can be increased to quickly relieve discomfort. DETAILED DESCRIPTION

[0020] Example 1

[0021] Ingredients: 20 parts snow pear, 10 parts honeysuckle, 5 parts tangerine peel, 10 parts kudzu root, 10 parts loquat, 15 parts momordica grosvenori, 5 parts licorice, 5 parts pistachio, 3 parts almond, 5 parts mint, 2 parts ginger, 3 parts lily. Mannitol is used at 20% of the weight of the granules; peach gum is used at 10% of the weight of the granules. Each portion is 100g.

[0022] Preparation method

[0023] 1. Raw material boiling: Mix the above raw materials, add 8 times the total weight of water, boil at 90 ° C for 4 hours, filter to remove the residue, and obtain the Chinese medicine extract.

[0024] 2. Concentration and granulation: The Chinese medicine extract was concentrated under reduced pressure at 60°C to 1 / 5 of the original volume, and granulated by spray drying. The inlet air temperature was 180°C, the outlet air temperature was 80°C, and the particle size of the Chinese medicine particles was controlled to be 180 mesh.

[0025] 3. Preparation of micropellets: The granulated Chinese medicine granules were divided into two equal parts. One part was mixed evenly with the corresponding weight of mannitol and made into immediate-release micropellets by extrusion spheronization. The other part was spray-coated with the corresponding weight of peach gum solution (peach gum dissolved in 50°C warm water to a concentration of 10%) and dried to obtain sustained-release micropellets.

[0026] 4. Tablet compression: Mix the immediate-release pellets and sustained-release pellets in a ratio of 1:3, add an appropriate amount of magnesium stearate as a lubricant, and press into tablets on a rotary tablet press with a pressure set to 15 kN to obtain oral tablets.

[0027] Example 2

[0028] Raw material formula

[0029] 10 parts snow pear, 5 parts honeysuckle, 15 parts tangerine peel, 5 parts kudzu root, 15 parts loquat, 5 parts momordica grosvenori, 3 parts licorice, 10 parts pistachio, 10 parts almond, 3 parts mint, 5 parts ginger, 1 part lily. Mannitol is used at a rate of 10% by weight of the corresponding Chinese medicine granules; peach gum is used at a rate of 15% by weight of the corresponding Chinese medicine granules. Each portion is 100g.

[0030] Preparation method

[0031] 1. Raw material boiling: After mixing the raw materials, add 5 times the total weight of water, boil at 100℃ for 3 hours, filter and concentrate to 1 / 4 of the original volume.

[0032] 2. Concentration and granulation: The concentrate was pre-frozen to -40°C using the freeze-drying granulation method, and then dried at a vacuum degree of 0.1 mbar and a temperature of -20°C for 24 hours to obtain Chinese medicine granules with a particle size of 100 mesh.

[0033] 3. Preparation of micropellets: Divide the Chinese medicine granules into two parts, mix one part with mannitol to make quick-release micropellets; and wrap the other part with peach gum solution to make sustained-release micropellets.

[0034] 4. Tablet molding: Mix the immediate-release pellets and sustained-release pellets in a ratio of 1:1 and compress them into tablets to obtain oral tablets.

[0035] Example 3

[0036] Raw material formula

[0037] 30 parts of snow pear, 15 parts of honeysuckle, 10 parts of tangerine peel, 15 parts of kudzu root, 5 parts of loquat, 10 parts of momordica grosvenori, 10 parts of liquorice, 3 parts of pistachio, 5 parts of almond, 10 parts of mint, 3 parts of ginger, and 5 parts of lily. The amount of mannitol is 30% of the weight of the corresponding Chinese medicine granules, and the amount of peach gum is 8% of the weight of the corresponding Chinese medicine granules. Each portion is 100g.

[0038] Preparation method

[0039] 2. Raw material boiling: add 10 times the total weight of the raw materials in water, boil at 100 ℃ for 3 hours, filter and concentrate to 1 / 6 of the original volume. Concentration and granulation: use spray drying method to granulate, and control the particle size of the Chinese medicine particles at 200 mesh.

[0040] 3. Micropellet preparation: Preparation of immediate-release micropellets and sustained-release micropellets.

[0041] 4. Tablet compression: Mix the immediate-release pellets and sustained-release pellets in a ratio of 1:5 and compress them into tablets to prepare buccal tablets.

[0042] Control example (blank control)

[0043] Raw material formula

[0044] Choose the common formula of ordinary throat lozenges without drug ingredients on the market: 60 parts of sucrose, 20 parts of glucose syrup, 3 parts of menthol, and 2 parts of edible flavoring.

[0045] Preparation method

[0046] The raw materials are mixed, granulated by hot melting, melted and mixed uniformly at 90° C., and then formed into tablets through a mold to make ordinary throat lozenges.

[0047] Experimental plan

[0048] Experiment 1: In vitro dissolution test

[0049] Purpose of the experiment

[0050] The release curves of the drug ingredients in the oral lozenges prepared in Examples 1-3 and the control example were tested to verify the synergistic drug release effect of the rapid-release pellets and the sustained-release pellets.

[0051] Experimental methods

[0052] 1. Take 20 tablets of each of the lozenges prepared in Examples 1-3 and 20 tablets of the control throat lozenges, and place them in the dissolution cups of the dissolution apparatus respectively. Add 900 mL of artificial saliva (pH 6.8) to each dissolution cup. The temperature is controlled at 37 ± 0.5 ° C and the speed is 50 r / min.

[0053] 2. 5 mL of samples were collected at time points of 0, 5, 10, 60, 120, and 240 min (and an equal amount of artificial saliva at the same temperature was added at the same time). After the samples were filtered through a 0.45 μm filter membrane, the concentrations of characteristic components such as chlorogenic acid in honeysuckle and sterculia lychnophora in sterculia lychnophora were determined by high performance liquid chromatography (HPLC).

[0054] Evaluation indicators

[0055] The cumulative dissolution curves of each component at different time points were plotted, the dissolution characteristics of the immediate-release stage (0-10 min) and the sustained-release stage (after 10 min) were analyzed, T50 (the time when the cumulative dissolution reached 50%) and T90 (the time when the cumulative dissolution reached 90%) were calculated, and the dissolution differences between the examples and the control were compared.

[0056] The experimental results are shown in Table 1

[0057]

[0058]

[0059] The experimental results show that the oral lozenges prepared in Examples 1-3 exhibit significant rapid-release and sustained-release synergistic drug release characteristics. In the rapid-release stage of 0-10 min, the cumulative dissolution of the characteristic ingredients of the lozenges of each example far exceeds that of the control example, among which the cumulative dissolution of Example 3 in 5 min reaches 32%, while the control example is only 5%, proving that the lozenges of the present invention can quickly release the active ingredients and quickly relieve throat discomfort. In the sustained-release stage after 10 min, the lozenges of the examples continuously release the drug, and the cumulative dissolution in 240 min exceeds 90%, while the control example is only 45%, and no obvious sustained-release characteristics are shown. In addition, the T50 and T90 of the lozenges of the examples are significantly better than those of the control example, indicating that the present invention achieves a dynamic balance between the drug release rate and the duration through the scientific ratio of rapid-release micropills and sustained-release micropills, effectively solving the problem of excessive initial concentration or insufficient concentration in the later stage of traditional lozenges.

[0060] Experiment 2: Stability Experiment

[0061] Experimental purpose: To investigate the quality stability of oral lozenges under different storage conditions and compare them with the control.

[0062] Experimental methods

[0063] 1. The lozenges prepared in Examples 1-3 and the control throat lozenges were stored under the following conditions:

[0064] Accelerated test: In a constant temperature and humidity chamber at 40℃±2℃ and relative humidity of 75%±5%, samples are collected for testing at 1, 2, 3 and 6 months.

[0065] Long-term test: Under the environment of 25℃±2℃ and relative humidity of 60%±10%, samples were collected for testing at the 3rd, 6th, 9th, 12th, 18th and 24th month.

[0066] 2. Inspection items include: appearance (whether there is discoloration, deformation, or adhesion), disintegration time (determined according to the method specified in the "Chinese Pharmacopoeia"), and microbial limits (detection of the number of bacteria, molds, and yeasts).

[0067] Evaluation indicators

[0068] By comparing the changes in various test items at different time points, the stability advantages of the example lozenges under peach gum coating and micro-pellet technology were analyzed, and the stability differences were compared with those of the control example ordinary throat lozenges.

[0069] The experimental results are shown in Table 2 (accelerated test for 6 months)

[0070] sample Appearance Disintegration time (min) Bacterial count (CFU / g) Mold count (CFU / g) Example 1 No change 8 <100 <10 Example 2 No change 10 <100 <10 Example 3 No change 7 <100 <10 Control Example Slight adhesion 15 500 80

[0071] The data from the 6-month accelerated test show that the oral lozenges of Examples 1-3 exhibit excellent quality stability under the action of peach gum wrapping and micropill technology. In terms of appearance, the lozenges of the examples showed no discoloration, deformation, or adhesion, while the control showed slight adhesion; in terms of disintegration time, the lozenges of the examples were stably maintained at 7-10 minutes, while the control was extended to 15 minutes; in the microbial limit test, the number of bacteria and molds in the lozenges of the examples met the standards (bacteria <100 CFU / g, mold <10 CFU / g), while the number of bacteria in the control was as high as 500 CFU / g, and the number of molds was 80 CFU / g. This shows that the lozenges of the present invention can effectively protect the drug ingredients, inhibit the growth of microorganisms, and extend the shelf life of the product under different storage conditions, with obvious stability advantages.

[0072] Experiment 3: Sensory evaluation and preliminary verification of clinical effects

[0073] Purpose of the experiment

[0074] The mouthfeel, user experience, and throat discomfort relief effect of the lozenges of the examples were evaluated and compared with those of the control examples.

[0075] Experimental methods

[0076] 1. Sensory evaluation: 30 healthy volunteers were recruited to rate the lozenges of Examples 1-3 and the throat lozenges of the control example in terms of taste (sweetness, cooling sensation), smell, and lozenge hardness (1-10 points).

[0077] 2. Preliminary Clinical Effect Verification: 60 patients with recent mild dry throat and cough symptoms were recruited and randomly divided into 4 groups (15 patients in each group). They were given the lozenges of Examples 1-3 and the throat lozenges of the control example, 3 times a day for 3 consecutive days. The relief of the dry throat and cough symptoms was recorded 10 minutes, 1 hour, and 3 hours after use (classified as significantly relieved, slightly relieved, and not relieved).

[0078] Evaluation indicators

[0079] The average sensory evaluation scores were calculated to analyze the differences in taste of lozenges with different formulas; and the symptom relief rates of patients in different groups were compared to verify the effectiveness of the lozenges of the present invention in relieving throat discomfort.

[0080] Experimental results

[0081] The sensory evaluation is shown in Table 3

[0082] sample Average taste Average odor score Average hardness score Example 1 8.2 8.5 8.0 Example 2 7.8 8.0 7.5 Example 3 8.0 8.3 8.2 Control Example 7.5 7.0 7.2

[0083] The clinical effects are shown in Table 4 (proportion of symptom relief after 3 days of use)

[0084] sample 10-minute significant relief rate 1h significant remission rate 3h significant remission rate Example 1 60％ 80％ 93％ Example 2 53％ 73％ 87％ Example 3 67％ 87％ 97％ Control Example 13％ 33％ 47％

[0085] Sensory evaluation results show that the oral lozenges of Examples 1-3 are highly rated in terms of mouthfeel, smell and hardness, with an average score exceeding 7.5 points, of which the mouthfeel and smell scores of Example 1 are 8.2 points and 8.5 points respectively, which are significantly better than the reference examples (mouthfeel 7.5 points, smell 7.0 points), indicating that the lozenges of the present invention have a good edible experience while taking into account drug efficacy. In terms of clinical effect, the embodiment lozenges have a significant effect on the relief of dry and itchy throat and cough symptoms. After 3 days of use, the significant relief rates of each embodiment at 10min, 1h, and 3h are significantly higher than those of the reference examples. The significant relief rate of Example 1 at 3h reaches 93%, while the reference examples are only 47%. This fully verifies that the lozenges of the present invention can not only quickly relieve throat discomfort, but also achieve long-term treatment by sustained-release effect, showing good effectiveness and applicability in actual applications.

[0086] The above is only an embodiment of the present invention, and the common knowledge such as the specific structure and characteristics of the scheme is not described in detail here. It should be pointed out that for those skilled in the art, without departing from the structure of the present invention, several variations and improvements can be made, which should also be regarded as the scope of protection of the present invention, and these will not affect the effect of the implementation of the present invention and the practicality of the patent. The scope of protection required by this application shall be based on the content of its claims, and the specific implementation methods and other records in the specification can be used to interpret the content of the claims.

Claims

1. An oral lozenge, characterized in that The invention is prepared from the following raw materials in parts by weight: 10-30 parts of snow pear, 5-15 parts of honeysuckle, 5-15 parts of orange peel, 5-15 parts of kudzu root, 5-15 parts of loquat, 5-15 parts of momordica grosvenori, 3-10 parts of liquorice, 3-10 parts of pistachio, 3-10 parts of almond, 3-10 parts of mint, 1-5 parts of ginger and 1-5 parts of lily; and also contains a certain proportion of mannitol for regulating sweetness and disintegration speed, and a certain proportion of peach gum for sustained release speed.

2. The oral lozenge according to claim 1, wherein: The invention is prepared from the following raw materials in parts by weight: 20 parts of snow pear, 10 parts of honeysuckle, 5 parts of orange peel, 10 parts of kudzu root, 10 parts of loquat, 15 parts of momordica grosvenori, 5 parts of liquorice, 5 parts of sterculia lychnophora, 3 parts of almond, 5 parts of mint, 2 parts of ginger and 3 parts of lily.

3. The method for preparing the oral lozenge according to any one of claims 1 or 2, wherein: Snow pear, honeysuckle, orange peel, kudzu root, loquat, momordica grosvenori, licorice, puffed sea, almond, ginger, mint, and lily are mixed in proportion, boiled with water, concentrated, and granulated to obtain Chinese medicine granules; part of the boiled Chinese medicine granules are mixed with mannitol to obtain quick-release micropills, and the other part of the boiled Chinese medicine granules are wrapped with peach gum to obtain sustained-release micropills; the quick-release micropills and sustained-release micropills are mixed in a ratio of 1:1 to 1:5, and then pressed into tablets to obtain oral lozenges.

4. The preparation method according to claim 3, wherein: The mixing ratio of the quick-release pellets and the sustained-release pellets is 1:3 to 1:

4.

5. The preparation method according to claim 4, characterized in that: In the step of adding water and boiling, the amount of water added is 5 to 10 times the total weight of the raw materials, the boiling temperature is 80 to 100° C., and the boiling time is 2 to 10 hours.

6. The preparation method according to claim 5, characterized in that: The granulation method is spray drying or freeze drying.

7. The preparation method according to claim 6, characterized in that: The particle size of the Chinese medicine granules after granulation is 100 to 200 meshes.

8. The preparation method according to claim 7, characterized in that: The dosage of mannitol is 10-30% of the weight of the Chinese medicine granules.

9. The preparation method according to claim 7, characterized in that: The dosage of peach gum is 5-15% of the weight of the Chinese medicine granules.

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