Orally dissolving film, racemic carbidopa orally dissolving film, and preparation method and preparation equipment thereof

Abstract

The application relates to the technical field of medicines, and discloses a novel oral dissolving film which is composed of the following components in mass fractions: soluble polymer 38-48 parts, plasticizer 10-20 parts, filling agent 5-15 parts, solvent 20-30 parts, acid-base regulator 0.5-2 parts, sweetening agent 1-3 parts, and medicine or other active ingredients 5-25 parts; on the basis of the oral dissolving film, the application further provides a racemic carbidopa oral dissolving film which is composed of the following components in mass fractions: racemic carbidopa 45-55 parts, the above-mentioned oral dissolving film 40-50 parts, sweetening agent 1-3 parts, essence 0.5-2 parts, and other auxiliary materials 1-8 parts; the oral dissolving film has good solubility, accurate dosage, high drug loading, and the preparation method is simple and easy for industrialized production.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of medicine, in particular to a mouth-dissolving film, a racemic carbidopa mouth-dissolving film and a preparation method and preparation equipment thereof. BACKGROUND

[0002] Diarrhea is a common disease that seriously endangers human health and quality of life, and people of all ages can suffer from it, especially infants, preschool children and the elderly, with a high incidence and mortality rate. The most common cause of diarrhea is intestinal infection. After the virus invades the patient's intestinal tract, it can cause the patient to have symptoms such as fever, vomiting and diarrhea. In severe cases, it can cause electrolyte imbalance and dehydration, and even endanger life.

[0003] Currently, oral salt solution and intestinal peristalsis inhibition are mainly used in clinical treatment of diarrhea. Oral salt solution can supplement water and electrolytes to prevent dehydration, but cannot inhibit intestinal secretion and has a slow onset. Anti-peristalsis drugs are opioid derivatives that work by inhibiting intestinal peristalsis and prolonging the retention time of intestinal contents, but they cannot inhibit the excessive secretion of water and electrolytes and can cause constipation and have many side effects. The above treatment methods are not effective in controlling symptoms in a short period of time.

[0004] Racemic carbidopa is an anti-diarrhea drug with high specificity for anti-secretion. It was developed by Bioproject Company in France and first marketed in France in 1993 under the trade name Tiorfan, in the form of capsules, and on the international market in 1997, for the treatment of acute diarrhea in adults. In 2001, the pediatric diarrhea indication was added. Racemic carbidopa is a compound in the form of a racemate that selectively inhibits peripheral enkephalinase, protects endogenous enkephalins from degradation, prolongs the physiological activity of endogenous enkephalins in the digestive tract, reduces the excessive secretion of water and electrolytes, and has a fast onset. Because it cannot cross the blood-brain barrier, it does not affect the enkephalinase activity of the central nervous system, so it has no central toxicity. Moreover, it only shows anti-diarrhea effect when excessive secretion occurs, without affecting the normal peristalsis of the gastrointestinal tract and the basal secretion of the intestinal tract. It has no side effects that are common in anti-diarrhea drugs, and is currently the best anti-diarrhea drug.

[0005] At present, the dosage forms containing racecadotril on the market include capsules, tablets, powders and oral disintegrating tablets. Among them, the oral disintegrating tablets of 6mg specification, the powders of 10mg and 30mg specification (trade name: Hidrasec) are suitable for children. There are many patents about the dosage forms of racecadotril and its pharmaceutical salts, such as fast disintegrating tablets containing racecadotril (CN1506043A), racecadotril granules and its production process (CN102166197A), racecadotril granules and its preparation method (CN103565750A), a dry suspension containing racecadotril and its preparation method (CN101103960A), a racecadotril liposome solid preparation (CN102133186A), a racecadotril oral fast-dissolving film and its preparation method (CN105919982A), dry powder formulation comprising racecadotril (EP1294372B1), new form of administration of racecadotril (EP2018158B1), racecadotril and pharmaceutical compositions thereof (EP2749270A1), new form of administration of enkephalinase inhibitor (EP2462922A1) and the like.

[0006] It is well known that when considering the dosage form of pediatric patients, it is particularly important to ensure patient compliance. Children may often have difficulty swallowing tablet or capsule preparations, with the risk of getting stuck in the throat, so it is particularly important to provide a dosage form that is easy to administer to children and has uniform content. Powders and granules act quickly, but may stick to the bag when poured, and racecadotril is a hydrophobic substance, so the granules may float or settle when brewing, so the patient may not be given the full dose. In comparison, the dosage of the film is more accurate. As a new type of drug preparation, the film is particularly suitable for children, the elderly and patients with difficulty swallowing due to digestive tract diseases and the like, and is also particularly suitable for patients who are not convenient to obtain water when traveling and the like. Whether the oral dissolving film can be compatible with a specific active ingredient, the oral dissolving film is a new type of oral drug delivery system, which has the advantages of rapid dissolution, easy to carry, convenient to use and the like. However, the existing oral dissolving film has the problems of poor solubility, inaccurate dosage, low drug loading and the like, which limits its application in clinical practice. Therefore, it is of great significance to develop an oral dissolving film with good solubility, accurate dosage and high drug loading for improving the efficacy of drugs and the compliance of patients.

[0007] European patent EP2749270A1 discloses an orally disintegrating tablet containing racemic caldotril, which uses an acrylic polymer or cellulose polymer coating to mask the taste via wet granulation.

[0008] Chinese patent CN105919982A discloses a racemic carbodotril oral instant dissolving film and its preparation method. The formulation disintegrates rapidly, using cyclodextrin as a taste masking agent, combined with sweeteners and bitterness inhibitors to effectively mask the bitterness of racemic carbodotril, significantly improving the palatability of the formulation. However, its drug loading is low; the preferred formulation contains only 5-10% racemic carbodotril, which may not meet the single-dose requirements for racemic carbodotril. Furthermore, due to the presence of sulfur in the molecule, racemic carbodotril has an unpleasant odor, which is not masked in the formulation, affecting patient compliance.

[0009] Chinese patent CN102133186A discloses a racemic caldotril liposome solid dosage form. By dissolving racemic caldotril to form liposomes, and then combining them with other excipients to form a solid dosage form, the solubility of racemic caldotril is improved, thereby increasing its bioavailability. However, the process is particularly complex, with significant material loss and high cost during preparation.

[0010] Chinese patent CN202110791165.5 discloses an orally dissolving film, a racemic carbomer orally dissolving film agent, and a method for preparing the same. The orally dissolving film comprises polyvinyl alcohol (PVA) and hydroxypropyl starch, with a mass ratio of PVA to hydroxypropyl starch of 5:1 to 6:1 and a degree of substitution of hydroxypropyl starch of 2 to 7%. The racemic carbomer orally dissolving film agent comprises the following components by weight percentage: 45-55% racemic carbomer, 38-48% orally dissolving film, 1-3% sweetener, 0.5-2% flavoring, and 0-8% other excipients. The orally dissolving film prepared by this invention does not use plasticizers, resulting in a higher cost and poorer performance of the prepared racemic carbomer orally dissolving film agent, with insufficient drug loading. Summary of the Invention

[0011] (a) Technical problems to be solved

[0012] To address the shortcomings of existing technologies, this invention provides an orally dissolving film, a racemic carbodotril orally dissolving film preparation method and preparation equipment, which has the advantages of good solubility, accurate dosage, high drug loading, and simple preparation method that is easy to industrialize. It solves the problems of poor solubility, inaccurate dosage, and low drug loading of existing orally dissolving films.

[0013] (II) Technical Solution

[0014] To achieve the above-mentioned oral dissolving film agent has good solubility, dose accuracy, high drug loading, and the preparation method is simple, easy to industrial production, the technical scheme is provided as follows: an oral dissolving film, comprising the following components by mass fraction: soluble polymer 38-48 parts, plasticizer 10-20 parts, filler 5-15 parts, solvent 20-30 parts, acid-base regulator 0.5-2 parts, sweetener 1-3 parts, drug or other active ingredients 5-25 parts.

[0015] Preferably, the soluble polymer is selected from one or more of hydroxypropyl methylcellulose, polyvinyl alcohol, polyethylene glycol.

[0016] Preferably, the plasticizer is selected from one or more of glycerol, propylene glycol, polyethylene glycol.

[0017] Preferably, the drug or other active ingredient uses microecological preparation, and the microecological preparation includes probiotics and prebiotics.

[0018] An oral dissolving film of racemic carbidopa, comprising the following components by mass fraction: racemic carbidopa 45-55 parts, oral dissolving film component composed of the above-mentioned oral dissolving film 40-50 parts, sweetener 1-3 parts, essence 0.5-2 parts, and other auxiliary materials 1-8 parts.

[0019] A method for preparing the above-mentioned oral dissolving film of racemic carbidopa, comprising the following steps:

[0020] Step S1: weigh each component according to the ratio;

[0021] Step S2: add the soluble polymer, plasticizer and filler into the solvent, heat and stir until completely dissolved to form a uniform polymer solution;

[0022] Step S3: add the acid-base regulator to the polymer solution to adjust the pH value of the solution to a range suitable for the oral environment;

[0023] Step S4: mix the racemic carbidopa, drug or other active ingredient with part of the solvent to form a drug suspension or drug solution, and then add it to the polymer solution with adjusted pH value and stir uniformly;

[0024] Step S5: add the sweetener and essence to the mixed solution and continue to stir uniformly;

[0025] Step S6: pour the mixed solution into a mold and dry it in a constant temperature and humidity environment, and after the solvent is completely volatilized, the oral dissolving film of racemic carbidopa is formed;

[0026] Step S7: take out the oral dissolving film of racemic carbidopa from the mold, cut, package and quality test.

[0027] Preferably, the temperature of the heating and stirring is 40-80 DEG C, and the stirring time is 1-4 hours.

[0028] Preferably, the temperature in the constant temperature and humidity environment is 20-40 DEG C, and the humidity is 20-60%.

[0029] Preferably, the drying time is 4-24 hours.

[0030] An equipment for preparing a racemic carbidopa oral dissolving film, comprising a machine body; a second motor for driving a stirring device is arranged on the top of the machine body; a button for starting or stopping the device is arranged on one side of the top end of the machine body at an oblique angle, and a cooling fan is arranged on the other side;

[0031] A stirring chamber for adding raw materials; a first motor is arranged on one side of the stirring chamber, and an arc surface is arranged on the bottom end of the stirring chamber;

[0032] A stirring device for heating and stirring the raw materials; a connecting piece is arranged on one end of the stirring device for fixed connection with the second motor; a first stirring plate and a second stirring plate are symmetrically arranged on the other end of the stirring device; and the first stirring plate and the second stirring plate are both fan-shaped arc surfaces.

[0033] Preferably, a plurality of supporting legs are arranged below the machine body, and an anti-skid pad is arranged below each supporting leg.

[0034] (Three) beneficial effects

[0035] Compared with the prior art, the present application provides an oral dissolving film, a racemic carbidopa oral dissolving film and a preparation method and preparation equipment thereof, and has the following beneficial effects:

[0036] (1) The oral dissolving film has good solubility and can be rapidly dissolved in the oral cavity, thereby improving the bioavailability and curative effect of the drug.

[0037] (2) The oral dissolving film is prepared by using an accurate proportioning and preparation method, thereby ensuring the dose accuracy and high drug loading of the drug.

[0038] (3) The preparation method is simple and easy to operate, is suitable for industrial production, and has a wide market application prospect. BRIEF DESCRIPTION OF DRAWINGS

[0039] Figure 1 A preparation procedure block diagram of the racemic carbidopa oral dissolving film is shown in the figure.

[0040] Figure 2 A schematic diagram of the overall structure of the preparation device of the racemic carbidopa oral dissolving film is shown in the figure.

[0041] Figure 3It is a front view of the preparation device of the racemic carbidopa oral dissolving film of the present application;

[0042] Figure 4 It is a structure diagram of the stirring device of the preparation device of the racemic carbidopa oral dissolving film of the present application.

[0043] 1, body; 11, support leg; 12, non-slip pad; 2, first motor; 3, stirring chamber; 31, arc surface; 4, stirring device; 41, connecting piece; 42, first stirring plate; 43, second stirring plate; 5, button; 6, second motor; 7, cooling fan. DETAILED DESCRIPTION

[0044] The technical solutions in the embodiments of the present application will be clearly and completely described below with reference to the drawings in the embodiments of the present application. Obviously, the described embodiments are only part of the embodiments of the present application, rather than all the embodiments. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art without creative labor fall within the scope of protection of the present application.

[0045] As shown in the drawings, Figure 1 An oral dissolving film includes the following components in mass parts: soluble polymer 38-48 parts, plasticizer 10-20 parts, filler 5-15 parts, solvent 20-30 parts, acid-base regulator 0.5-2 parts, sweetener 1-3 parts, and drug or other active ingredient 5-25 parts.

[0046] In the present embodiment, the soluble polymer is selected from one or more of hydroxypropyl methylcellulose, polyvinyl alcohol, and polyethylene glycol, most preferably hydroxypropyl methylcellulose.

[0047] In the present embodiment, the plasticizer is selected from one or more of glycerol, propylene glycol, and polyethylene glycol, most preferably polyethylene glycol.

[0048] In the present embodiment, the filler is at least one of hydroxypropyl starch, maltodextrin, and mannitol, most preferably hydroxypropyl starch.

[0049] In the present embodiment, the solvent is ethanol.

[0050] In the present embodiment, the sweetener is sucrose.

[0051] In the present embodiment, the acid-base regulator is at least one of malic acid, citric acid, and tartaric acid, and at least one of sodium hydroxide and sodium bicarbonate, most preferably citric acid and sodium bicarbonate.

[0052] In the present embodiment, the drug or other active ingredient is a microecological preparation, and the microecological preparation includes probiotics and prebiotics.

[0053] A racemic carbidopa oral dissolving film preparation, in this embodiment, includes the following components in mass parts: racemic carbidopa 45-55 parts, oral dissolving film component consisting of any of the above oral dissolving films (not containing drugs or other active ingredients) 40-50 parts, sweetener 1-3 parts, flavoring 0.5-2 parts, other auxiliary materials 1-8 parts.

[0054] In this embodiment, the sweetener is at least one of saccharin, aspartame, sucrose, fructose, and most preferably sucrose.

[0055] In this embodiment, the flavoring is a commercially available edible flavoring.

[0056] In this embodiment, the other auxiliary materials are at least one of starch and cellulose, and most preferably cellulose.

[0057] As shown in Figures 2-4 An apparatus for preparing a racemic carbidopa oral dissolving film preparation, comprising a machine body 1; a second motor 6 is arranged inside the machine body 1 for driving the stirring device; a button 5 is arranged on one side of the top end of the machine body 1 for starting or stopping the device; a cooling fan 7 is arranged on the other side of the top end of the machine body 1.

[0058] A stirring chamber 3 is arranged for adding raw materials; a first motor 2 is arranged on one side of the stirring chamber 3; an arc surface 31 is arranged at the bottom end of the stirring chamber 3.

[0059] A stirring device 4 is arranged for heating and stirring the raw materials; a connecting piece 41 is arranged at one end of the stirring device 4 for fixed connection with the second motor 6; a first stirring plate 42 and a second stirring plate 43 are symmetrically arranged at the other end of the stirring device 4; the first stirring plate 42 and the second stirring plate 43 are both fan-shaped arc surfaces; the machine body is the main structure of the apparatus, providing support and protection; a second motor is arranged inside the machine body for driving the stirring device; a button is arranged on one side of the top end of the machine body for starting or stopping the apparatus; a cooling fan is arranged on the other side of the top end of the machine body to prevent overheating of the apparatus; the stirring chamber is where the raw materials are added, and its design should facilitate the addition and removal of raw materials; a first motor is arranged on one side of the stirring chamber (the purpose of the first motor is not explicitly stated here, but it may be used for auxiliary stirring or controlling the stirring speed, etc.); an arc surface is arranged at the bottom end of the stirring chamber, which helps to evenly distribute and stir the raw materials; the stirring device is the core part of the apparatus, used for heating and stirring the raw materials; a connecting piece is arranged at one end of the stirring device for fixed connection with the second motor to realize power transmission; a first stirring plate and a second stirring plate are symmetrically arranged at the other end of the stirring device; both are fan-shaped arc surfaces, which can increase the uniformity and efficiency of stirring.

[0060] As shown in Figure 2As shown, the machine body 1 is provided with several support feet 11, and each support foot 11 is correspondingly provided with a non-slip pad 12 below. The main function of the several support feet 11 provided below the machine body 1 is to provide stable support for the entire device. The weight of the device is evenly distributed on the ground through the support feet, ensuring that the device will not affect the stirring effect and product quality due to shaking or tilting during operation. The main purpose of the non-slip pad 12 correspondingly provided below each support foot 11 is to increase the friction between the device and the ground, preventing the device from sliding or shifting due to vibration or external force during the stirring process. This helps to ensure the stability and safety of the device during operation. Non-slip pads 12 are usually made of soft materials such as rubber or silicone. They not only have good anti-slip performance, but also can reduce the pressure and wear on the ground, protecting the ground from damage. The material and structural design of the non-slip pad also helps to reduce noise and vibration generated during the operation of the device. By absorbing and dispersing vibration energy, noise levels are reduced, improving the comfort of the device in use. Although the main function of the non-slip pad is to prevent slipping, they are usually designed to have a certain elasticity and softness. This allows the device to be easily moved and adjusted when necessary by applying a certain amount of force to overcome the friction of the non-slip pad. Example 1

[0061] A racemic carbidopa oral film was prepared:

[0062] According to the mass fraction, racemic carbidopa 45 parts, oral film 40 parts, sucrose 1 part, edible flavor 0.5 part, cellulose 1 part; add the soluble polymer, plasticizer and filler into the solvent, heat to 40-80℃ and stir for 1-4h until completely dissolved to form a uniform polymer solution; add the acid-base regulator to the polymer solution to adjust the pH value of the solution to 6.6-7.1; mix the racemic carbidopa, drugs or other active ingredients with part of the solvent to form a drug suspension or drug solution, then add it to the polymer solution with adjusted pH value, stir for 0.5-1 hour; add sucrose and edible flavor to the mixed solution and continue stirring for 0.5-1 hour; pour the mixed solution into the mold and place it in a constant temperature and humidity environment with a temperature of 20-40℃ and a humidity of 40%-60% for drying for 4-24 hours. After the solvent is completely volatilized, a racemic carbidopa oral film is formed; take the racemic carbidopa oral film out of the mold, cut, package and quality test. Example 2

[0063] A racemic carbidopa oral film was prepared:

[0064] According to the mass fraction of racemate cadotuo 50 parts, the above-mentioned oral soluble film 40 parts, sucrose 1 part, edible flavor 0.5 part, cellulose 1 part; the soluble polymer, plasticizer and filler are added to the solvent, heated to 40-80°C and stirred for 1-4h to completely dissolve, forming a uniform polymer solution; add acid-base regulator to the polymer solution, adjust the pH value of the solution to 6.6-7.1; mix racemate cadotuo, drugs or other active ingredients with part of the solvent to form a drug suspension or drug solution, then add it to the polymer solution with adjusted pH value, stir for 0.5-1 hour; add sucrose and edible flavor to the mixed solution, continue to stir for 0.5-1 hour; pour the mixed solution into the mold, place it in a constant temperature and humidity environment with temperature of 20-40°C and humidity of 40%-60% for drying for 4-24 hours, until the solvent is completely volatilized, forming a racemate cadotuo oral soluble film; take the racemate cadotuo oral soluble film out of the mold, cut, package and quality test. Example 3

[0065] Prepare a racemate cadotuo oral soluble film:

[0066] According to the mass fraction of racemate cadotuo 50 parts, the above-mentioned oral soluble film 40 parts, sucrose 1 part, edible flavor 0.5 part, cellulose 1 part; the soluble polymer, plasticizer and filler are added to the solvent, heated to 40-80°C and stirred for 1-4h to completely dissolve, forming a uniform polymer solution; add acid-base regulator to the polymer solution, adjust the pH value of the solution to 6.6-7.1; mix racemate cadotuo, drugs or other active ingredients with part of the solvent to form a drug suspension or drug solution, then add it to the polymer solution with adjusted pH value, stir for 0.5-1 hour; add sucrose and edible flavor to the mixed solution, continue to stir for 0.5-1 hour; pour the mixed solution into the mold, place it in a constant temperature and humidity environment with temperature of 20-40°C and humidity of 40%-60% for drying for 4-24 hours, until the solvent is completely volatilized, forming a racemate cadotuo oral soluble film; take the racemate cadotuo oral soluble film out of the mold, cut, package and quality test. Example 4

[0067] Prepare a racemate cadotuo oral soluble film:

[0068] According to the mass fraction, 55 parts of racemic carbidopa, 45 parts of the above-mentioned oral soluble film, 3 parts of sucrose, 2 parts of edible flavor, and 8 parts of cellulose are weighed. The soluble polymer, plasticizer and filler are added to the solvent, heated to 40-80°C and stirred for 1-4h to completely dissolve, forming a uniform polymer solution. Add acid-base regulator to the polymer solution to adjust the pH of the solution to 6.6-7.1. Mix racemic carbidopa, drugs or other active ingredients with part of the solvent to form a drug suspension or drug solution, then add it to the polymer solution with adjusted pH value, stir for 0.5-1 hour. Add sucrose and edible flavor to the mixed solution and continue stirring for 0.5-1 hour. Pour the mixed solution into the mold and place it in a constant temperature and humidity environment with a temperature of 20-40°C and a humidity of 40%-60% for drying for 4-24 hours. After the solvent is completely volatilized, a racemic carbidopa oral soluble film is formed. The racemic carbidopa oral soluble film is removed from the mold and cut, packaged and quality tested. Example 5

[0069] A racemic carbidopa oral soluble film is prepared:

[0070] According to the mass fraction, 55 parts of racemic carbidopa, 45 parts of the above-mentioned oral soluble film, 3 parts of sucrose, 2 parts of edible flavor, and 8 parts of cellulose are weighed. The soluble polymer, plasticizer and filler are added to the solvent, heated to 40-80°C and stirred for 1-4h to completely dissolve, forming a uniform polymer solution. Add acid-base regulator to the polymer solution to adjust the pH of the solution to 6.6-7.1. Mix racemic carbidopa, drugs or other active ingredients with part of the solvent to form a drug suspension or drug solution, then add it to the polymer solution with adjusted pH value, stir for 0.5-1 hour. Add sucrose and edible flavor to the mixed solution and continue stirring for 0.5-1 hour. Pour the mixed solution into the mold and place it in a constant temperature and humidity environment with a temperature of 20-40°C and a humidity of 40%-60% for drying for 4-24 hours. After the solvent is completely volatilized, a racemic carbidopa oral soluble film is formed. The racemic carbidopa oral soluble film is removed from the mold and cut, packaged and quality tested.

[0071] The racemic carbidopa oral soluble film prepared in Examples 1-5 is tested for solubility and drug loading:

[0072] I. Solubility test

[0073] A certain amount of racemic carbidopa oral soluble film sample is placed in a volumetric flask, and a certain amount of simulated saliva solution is added. Stir with a magnetic stirrer under constant temperature conditions. Record the time required for complete dissolution of the drug, and measure the drug concentration in the solution. According to the measured drug concentration and the amount of sample added, the solubility of racemic carbidopa in the selected solvent is calculated.

[0074] II. Drug loading test

[0075] A certain amount of racemic carbidopa oral dissolving film sample is dried to remove solvent and moisture, and the drug in the dried sample is extracted using a suitable solvent. Ensure that the drug is completely dissolved in the solvent during extraction. The content of racemic carbidopa in the extract is determined by high performance liquid chromatography (HPLC) or other appropriate methods. The drug loading of the racemic carbidopa oral dissolving film is calculated based on the determined drug content and the total mass of the sample.

[0076] Notes:

[0077] 1. Before conducting the experiment, ensure that all equipment and reagents are clean and dry to avoid interference with the experimental results.

[0078] 2. When performing the solubility test, pay attention to controlling the temperature, stirring speed and selection of solvent to ensure the stability and repeatability of the experimental conditions.

[0079] 3. When performing the drug loading test, pay attention to the selection of extraction method and optimization of extraction conditions to ensure that the drug can be completely extracted from the sample.

[0080] 4. Strictly follow the safety operation procedures during the experiment to avoid waste of drugs and pollution of the environment.

[0081] The solubility and drug loading of the racemic carbidopa oral dissolving film obtained through the test experiment are shown in Table 1 below:

[0082]

[0083] Based on the data in Table 1 above, it can be concluded that within a certain mass fraction range of each component, the solubility and drug loading of the racemic carbidopa oral dissolving film prepared under the condition of constant mass fraction of racemic carbidopa are lower, and the solubility and drug loading of the racemic carbidopa oral dissolving film prepared under the condition of constant mass fraction of oral dissolving film are higher. Therefore, the racemic carbidopa oral dissolving film prepared by using about 50 parts of racemic carbidopa, about 40 parts of the oral dissolving film, about 1 part of sweetener, about 0.5 part of flavor and about 1 part of other auxiliary materials has the best solubility and high drug loading.

[0084] In summary, the oral dissolving film of the present application has good solubility and can dissolve rapidly in the oral cavity, improving the bioavailability and efficacy of the drug. The oral dissolving film of the present application uses precise proportioning and preparation method to ensure the accuracy of the drug dosage and high drug loading. The preparation method of the present application is simple and easy to operate, suitable for industrial production, and has broad market application prospects

[0085] It has to be noted that, in the present document, the terms "first", "second", etc. merely serve to identify a subject or action, without necessarily requiring or implying any such actual relationship or order between such subjects or actions. Moreover, the terms "comprises", "comprising", or any other variation thereof, are intended to cover a non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements does not include only those elements but can include other elements not expressly listed or inherent to such process, method, article, or apparatus. An element proceeded by "comprises... a" does not, without more constraints, exclude the presence of additional identical elements in the process, method, article, or apparatus that comprises the element.

[0086] While embodiments of the application have been shown and described, it is to be understood that the application is not limited to the details of the embodiments described, since numerous further modifications and changes can be apparent to one skilled in the art without departing from the spirit and scope of the application as defined by the appended claims and their equivalents.

Claims

1. A racemic carbohydrate solvent, characterized in that, The product comprises the following components in parts by weight: racemic caldotril: 45-55 parts; oral film component: 40-50 parts; sweetener: 1-3 parts; Fragrance: 0.5-2 parts; Other auxiliary materials: 1-8 parts; The oral dissolving film component comprises the following components in parts by mass: Soluble polymer: 38-48 parts, hydroxypropyl methylcellulose; Plasticizer: 10-20 parts, selected from one or more of glycerin, propylene glycol, and polyethylene glycol; Filler: 5-15 parts; Solvent: 20-30 parts, wherein the solvent is ethanol; pH adjuster: 0.5-2 parts, including citric acid and sodium bicarbonate, used to adjust the pH of the solution to 6.6-7.1; Sweetener: 1-3 parts; Microecological preparations: 5-25 servings, including probiotics and prebiotics.

2. A method for preparing the racemic carbolic acid solvent of claim 1, characterized in that, Includes the following steps: Step S1: Weigh each component according to the proportions; Step S2: Add the soluble polymer, plasticizer, and filler to the solvent, heat and stir until completely dissolved to form a homogeneous polymer solution; Step S3: Add an acid-base adjuster to the polymer solution to adjust the pH value of the solution to a range suitable for the oral environment; Step S4: Mix racemic caldotril, the drug or other active ingredient with a portion of the solvent to form a drug suspension or drug solution, and then add it to the polymer solution with the pH adjusted, and stir until homogeneous; Step S5: Add sweetener and flavoring to the mixed solution and continue stirring until well combined; Step S6: Pour the mixed solution into a mold and place it in a constant temperature and humidity environment to dry. After the solvent has completely evaporated, a racemic carbolic acid solvent is formed. Step S7: Remove the racemic carbohydrate solvent from the mold, and then cut, package, and inspect its quality. The temperature in the constant temperature and humidity environment is 20℃-40℃, the humidity is 20%-60%, and the drying time is 4h-24h.

3. The method according to claim 2, characterized in that, The heating and stirring temperature is 40℃-80℃, and the stirring time is 1h-4h.

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