Sotalol hydrochloride film for oral instant administration and its preparation method

Abstract

This application relates to the field of oral instant-dissolving film preparation technology and provides a sotalol hydrochloride film for oral instant-dissolving drug delivery. The components of the sotalol hydrochloride film of this application include: sotalol hydrochloride, film-forming material, filler, and flavoring agent. The sotalol hydrochloride film of this application uses sotalol hydrochloride as the active ingredient, which can exert an antiarrhythmic effect and regulate myocardial cell repolarization; the use of polyvinyl alcohol as the film-forming material provides the film's formability and flexibility; the addition of mannitol as a filler helps increase the film's solids content, adjust the film's thickness and uniformity, and improve the formability of the oral instant-dissolving film; steviol glycosides and / or blueberry flavoring, as flavoring agents, can mask the bitterness of sotalol hydrochloride, while giving the film a light pink appearance and blueberry flavor, further improving the sensory experience. Therefore, the sotalol hydrochloride film of this application has more accurate dosage, is more convenient to swallow, has a more suitable taste, and is applicable to a wider range of scenarios.

Description

Technical Field

[0001] This application relates to the field of oral instant-dissolving film technology, and in particular to a sotalol hydrochloride film for oral instant-dissolving administration and its preparation method. Background Technology

[0002] Sotalol hydrochloride, a class III antiarrhythmic drug, works by regulating the repolarization process of myocardial cells. Clinically, it is primarily used to treat ventricular and supraventricular arrhythmias in children, such as reducing the frequency of premature ventricular contractions (PVCs) and lowering the heart rate of supraventricular tachycardia. It is a key drug in the treatment of pediatric arrhythmias. Currently, marketed formulations of this drug are mainly in tablet and injectable forms. Tablets are difficult to control dosage, have poor swallowing safety, and low patient compliance, while injectable forms have limited applicability, high administration dependence, and cannot meet long-term treatment needs. Therefore, there is an urgent need to research a dedicated dosage form for the treatment of pediatric arrhythmias that is accurate in dosage, convenient to swallow, has a palatable taste, and is applicable to a wide range of scenarios. Summary of the Invention

[0003] In view of this, this application aims to provide a sotalol hydrochloride film formulation for oral administration that can improve the accuracy of dosage, ease of swallowing, and palatability.

[0004] To achieve the above objectives, the technical solution of this application is implemented as follows:

[0005] A sotalol hydrochloride film for oral administration, wherein the components of the sotalol hydrochloride film include: sotalol hydrochloride, film-forming material, filler, and flavoring agent.

[0006] The film-forming material is any one or more of hydroxypropyl methylcellulose, polyvinyl alcohol, pullulan, povidone, sodium carboxymethyl cellulose, or hydroxypropyl cellulose; and / or,

[0007] The filler is mannitol; and / or,

[0008] The flavoring agent includes flavoring agent A and flavoring agent B, wherein flavoring agent A is any one or more of steviol glycosides, sucralose, or aspartame; and / or,

[0009] The flavoring agent B is any one or more of blueberry flavoring, menthol, strawberry flavoring, or orange flavoring.

[0010] Furthermore, the mass ratio of the sotalol hydrochloride to the film-forming material, the filler, the flavoring agent A, and the flavoring agent B is between (110-130):(220-250):(100-140):(6-10):(8-12).

[0011] Compared with related technologies, this application has the following advantages:

[0012] The sotalol hydrochloride film of this application uses sotalol hydrochloride as the active ingredient, which can exert an antiarrhythmic effect and regulate myocardial cell repolarization. The use of polyvinyl alcohol and other materials as film-forming materials can provide the film with good formability and flexibility, ensuring that the film is easy to peel off and durable. The addition of mannitol and other fillers can help increase the solids content of the film, adjust the thickness and uniformity of the film, and improve the formability of the oral instant film. Stevioside and blueberry flavoring, as flavoring agents, can mask the bitterness of sotalol hydrochloride, improve the acceptance of the medication in children, and at the same time give the film a light pink appearance and blueberry flavor, further improving the sensory experience.

[0013] Polyvinyl alcohol (PVA) ensures film formation, while mannitol reduces the excessive flexibility of the PVA film, preventing it from adhering to the oral mucosa. Simultaneously, mannitol's water solubility accelerates film disintegration in saliva, achieving a synergistic balance between easy formation and rapid disintegration. Furthermore, the high sweetness of steviol glycosides quickly masks the bitterness of the medication, while the blueberry flavor prolongs oral comfort. This combination addresses children's resistance to bitter medications.

[0014] Therefore, the sotalol hydrochloride film formulation of this application has more accurate dosage, is easier to swallow, has a more suitable taste, and is applicable to a wider range of scenarios.

[0015] This application also discloses a method for preparing a sotalol hydrochloride film, the method comprising:

[0016] Sotalol hydrochloride was dissolved in a solvent to prepare a solution of the active pharmaceutical ingredient;

[0017] The film-forming material is added to the raw drug solution, swollen, and then heated to dissolve, thus obtaining a mixed drug solution.

[0018] The filler and flavoring agent are added sequentially to the mixed medicinal solution and dissolved to obtain the medicinal solution;

[0019] Degas the medicinal solution;

[0020] The deaerated drug solution is coated, dried, and then cut to obtain the sotalol hydrochloride film.

[0021] Furthermore, the step of adding the film-forming material to the active pharmaceutical ingredient solution, performing a swelling treatment, and then heating to dissolve it to obtain a mixed pharmaceutical solution includes:

[0022] The film-forming material is slowly added to the active pharmaceutical ingredient solution, and stirred until it is completely submerged.

[0023] After immersion, the mixture is allowed to stand until the film-forming material swells, then placed in a water bath at a first preset temperature and stirred at a first preset speed until the polyvinyl alcohol is completely dissolved, thus obtaining the mixed drug solution.

[0024] Furthermore, the first preset temperature is between 58℃ and 62℃;

[0025] The first preset speed is between 300 rpm and 400 rpm.

[0026] Furthermore, the step of sequentially adding the filler and flavoring agent to the mixed medicinal solution to dissolve them, thereby obtaining the medicinal solution, includes:

[0027] The filler is added to the mixed solution, and the solution is stirred in a water bath at a second preset temperature and at a second preset speed until the filler is completely dissolved.

[0028] After the filler is completely dissolved, the flavoring agent is added, and the mixture is stirred in a water bath at a third preset temperature and at a third preset speed until the flavoring agent is evenly dispersed to obtain the medicine solution.

[0029] Furthermore, both the second preset temperature and the third preset temperature are between 58℃ and 62℃;

[0030] The second preset speed is between 300 rpm and 400 rpm;

[0031] The third preset speed is between 200 rpm and 300 rpm.

[0032] Furthermore, the step of preparing the sotalol hydrochloride film by coating, drying, and cutting the deaerated drug solution includes:

[0033] Slowly pour the deaerated medicine onto the film-laying plate, and make the medicine evenly cover the surface of the film-laying plate to a preset thickness;

[0034] The film-coating plate, which is uniformly covered with the medicinal liquid, is dried at a fourth preset temperature for a first preset time.

[0035] After drying, the membrane is cooled and cut to a preset size to obtain the sotalol hydrochloride membrane.

[0036] Furthermore, the preset thickness is between 0.8mm and 1.2mm;

[0037] The fourth preset temperature is between 45℃ and 55℃;

[0038] The first preset time is between 50 min and 70 min.

[0039] Compared with related technologies, this application has the following advantages:

[0040] The preparation method of the sotalol hydrochloride film of this application adopts solvent casting technology. Through the process of "excipient dissolution - drug solution preparation - defoaming - film laying - drying - cutting", an oral instant film with appropriate thickness, rapid disintegration and good taste is obtained.

[0041] This application also proposes an oral instant-dissolving drug, which includes the above-mentioned sotalol hydrochloride film, or the oral instant-dissolving drug includes sotalol hydrochloride film prepared by the above-mentioned preparation method. Attached Figure Description

[0042] The accompanying drawings, which form part of this application, are used to provide a further understanding of this application. The illustrative embodiments and descriptions of this application are used to explain this application and do not constitute an undue limitation of this application. In the drawings:

[0043] Figure 1 This is a flowchart illustrating the preparation method of the sotalol hydrochloride film agent described in the embodiments of this application. Detailed Implementation

[0044] To make the technical solution and advantages of this application clearer, the following detailed description is provided in conjunction with the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely illustrative and not intended to limit the scope of this application.

[0045] It should be noted that, unless otherwise specified, the embodiments and features described in this application can be combined with each other.

[0046] For items where specific conditions are not specified in this application, conventional conditions or conditions recommended by the manufacturer of the equipment used shall apply. For items where the manufacturer of the reagents or instruments used is not specified, conventional products that can be purchased commercially shall be used. As for the technical means or processes involved, if specific conditions are not specified, they shall be carried out in accordance with the existing methods in the relevant field.

[0047] An embodiment of the first aspect of this application provides a sotalol hydrochloride film for oral administration, which can improve the accuracy of dosage, ease of swallowing and taste compatibility.

[0048] In related technologies, sotalol hydrochloride tablets use sotalol hydrochloride as the active ingredient, supplemented with conventional tablet excipients such as microcrystalline cellulose, lactose, and magnesium stearate. They are solid tablet formulations produced through mixing, granulation, and compression, with common specifications of 40mg / tablet and 80mg / tablet. Its efficacy lies in its absorption via the gastrointestinal tract after oral administration. By regulating potassium ion channels in myocardial cells, it prolongs the action potential duration and effective refractory period, thereby inhibiting arrhythmias. It is suitable for the long-term treatment of conditions such as premature ventricular contractions and supraventricular tachycardia in children.

[0049] Sotalol hydrochloride injection uses sotalol hydrochloride as the active ingredient, with the addition of sodium chloride, water for injection, and other excipients to prepare a sterile aqueous solution. It is typically available in 5mg / vial or 10mg / vial specifications. Its efficacy lies in its direct entry into the bloodstream via intravenous injection, providing rapid onset of action. It is suitable for the emergency control of acute arrhythmias in children (such as malignant ventricular tachycardia).

[0050] However, both of the above dosage forms have certain drawbacks. When tablets are administered through the gastrointestinal tract, the drug comes into direct contact with the gastric mucosa, which can easily cause gastrointestinal irritation reactions such as nausea and abdominal distension in children. In addition, tablets need to be divided for administration (the dosage for children is usually 1 / 4 to 1 / 2 of that for adults). Insufficient division precision can easily lead to dosage deviation, which in turn can cause dose-related adverse reactions such as bradycardia and QT interval prolongation. Injectables have limited application scenarios and are highly dependent on operation, which cannot meet the needs of long-term treatment.

[0051] In view of this, in order to overcome the shortcomings of the related technologies, the overall design of the sotalol hydrochloride film agent in this embodiment includes: sotalol hydrochloride, film-forming material, filler, and flavoring agent.

[0052] It is worth noting that the film-forming material is any one or more of hydroxypropyl methylcellulose, polyvinyl alcohol, pullulan, povidone, sodium carboxymethyl cellulose, or hydroxypropyl cellulose; the filler is mannitol; the flavoring agents include flavoring agent A and flavoring agent B, flavoring agent A is any one or more of steviol glycosides, sucralose, or aspartame; flavoring agent B is any one or more of blueberry flavoring, menthol, strawberry flavoring, or orange flavoring.

[0053] Specifically, sotalol hydrochloride, a class III antiarrhythmic drug, works by regulating the repolarization process of myocardial cells. Clinically, it is mainly used to treat ventricular and supraventricular arrhythmias in children, such as reducing the frequency of premature ventricular contractions and lowering the heart rate of supraventricular tachycardia. It is one of the key drugs in the treatment of arrhythmias in children. In this embodiment, it is used as the active ingredient to exert its antiarrhythmic effect and regulate myocardial cell repolarization.

[0054] Preferred film-forming materials include, for example, polyvinyl alcohol (PVA). PVA is a linear polyether compound formed by the condensation of ethylene oxide and water. It is readily soluble in polar solvents such as water and ethanol, and can dissolve rapidly in oral saliva, avoiding any residual foreign body sensation. This meets the core requirement of "rapid dissolution / slow release" for oral films. In this embodiment, it is used as a film-forming agent to provide the film with formability and flexibility, ensuring that the film is easy to peel off and fold-resistant.

[0055] Mannitol is a preferred filler, for example. Mannitol is readily soluble in water and slightly soluble in ethanol. It dissolves at a moderate rate in oral saliva, and its dissolution is accompanied by a slight endothermic effect, providing a cooling sensation and effectively masking the bitterness or unpleasant taste of the medication, thus improving patient compliance. Its aqueous solution has low viscosity and will not significantly increase the consistency of the film coating solution, facilitating processing. In this embodiment, it is used as a filler to improve film brittleness, enhance the taste after oral dissolution, and aid in drug dispersion.

[0056] Flavoring agents may preferably include flavoring agent A and flavoring agent B, wherein flavoring agent A may preferably be any one or more of steviol glycosides, sucralose or aspartame.

[0057] Specifically, steviol glycosides are natural sweeteners extracted from the stevia plant (Stevia repens). Steviol glycosides are approximately 200-300 times sweeter than sucrose, and have an extremely low sweetness threshold. Only microgram to milligram doses are needed in drug formulations to achieve the desired sweetness adjustment, avoiding interference from high-dose additions on key properties such as drug formulation stability and dissolution rate. In terms of taste, steviol glycosides exhibit a cool and lingering flavor profile, without the stickiness and aftertaste common with sucrose sweeteners. Furthermore, their molecular structure and binding mechanism with taste receptors effectively block the transmission of unpleasant flavor signals such as bitterness, astringency, or spiciness. This "flavor masking effect" stems not only from their competitive binding to taste receptors but also from their synergistic effect with their cooling sensation, significantly neutralizing the irritating taste of active pharmaceutical ingredients (such as alkaloids, antibiotics, and cardiovascular drugs), thereby improving medication adherence, especially among specific populations. In this embodiment, it is used as a flavoring agent to mask the bitterness of sotalol hydrochloride and improve the acceptance of the medication by children.

[0058] Flavoring agent B is preferably any one or more of blueberry flavoring, menthol, strawberry flavoring, or orange flavoring.

[0059] Specifically, blueberry flavoring is a type of compound flavoring with blueberry fruit flavor as its core. The fruity components of blueberry flavoring (such as styrax acetate, limonene, and blueberry ketone) can activate oral taste and olfactory receptors, weakening the sensitivity of bitter taste receptors in drugs through a dual effect of "aroma compensation" and "taste masking." Simultaneously, it forms a synergistic effect with the sweetness of sweeteners, constructing a "sweet and sour balance" taste system and reducing the subjective perception of unpleasant drug odors. In this embodiment, it is used as a flavoring agent, giving the film a light pink appearance and blueberry flavor, further improving the sensory experience.

[0060] In the above-mentioned sotalol hydrochloride film preparation, the mass ratio of sotalol hydrochloride to film-forming material, filler, flavoring agent A, and flavoring agent B is preferably between (110-130):(220-250):(100-140):(6-10):(8-12).

[0061] In this embodiment, the sotalol hydrochloride film formulation ensures film formation through the film-forming properties of polyvinyl alcohol (PVA), while mannitol filler reduces excessive flexibility of the PVA film, preventing adhesion to the oral mucosa. Simultaneously, mannitol's water solubility accelerates film disintegration in saliva, achieving a synergistic balance between easy formation and rapid disintegration. Furthermore, the high sweetness of steviol glycosides as a flavoring agent quickly masks the bitterness of the medication, while blueberry flavoring prolongs oral comfort. This combination addresses children's resistance to bitter medications. Therefore, this embodiment of the sotalol hydrochloride film formulation offers more accurate dosage, easier swallowing, a more suitable taste, and wider applicability.

[0062] An embodiment of the second aspect of this application provides a method for preparing a sotalol hydrochloride film, the method comprising the following steps:

[0063] Step S1: Dissolve sotalol hydrochloride in a solvent to obtain a solution of the active pharmaceutical ingredient.

[0064] In step S1 above, sotalol hydrochloride is dissolved in a solvent to prepare a drug substance solution. As a preferred embodiment, for example, sotalol hydrochloride can be dissolved in distilled water and sonicated until the sotalol hydrochloride is completely dissolved to prepare a drug substance solution.

[0065] Step S2: Add the film-forming material to the raw drug solution, perform swelling treatment, and then heat to dissolve to obtain a mixed drug solution.

[0066] In step S2 above, the film-forming material is added to the drug substance solution, swollen, and then heated to dissolve to obtain a mixed drug solution. As a preferred embodiment, this may include, for example, slowly adding the film-forming material to the drug substance solution and stirring until completely submerged.

[0067] After immersion, the mixture is allowed to stand until the film-forming material swells. Then, it is placed in a water bath at a first preset temperature and stirred at a first preset speed until the film-forming material is completely dissolved, thus obtaining a mixed drug solution.

[0068] The first preset temperature mentioned above is preferably between 58°C and 62°C.

[0069] The first preset speed is preferably between 300 rpm and 400 rpm.

[0070] Step S3: Add the filler and flavoring agent to the mixed medicine solution in sequence to dissolve them and obtain the medicine solution.

[0071] In step S3 above, the filler and flavoring agent are added sequentially to the mixed medicinal solution to dissolve them, thus obtaining the medicinal solution. As a preferred embodiment, this may include, for example:

[0072] Add the filler to the mixed solution, and stir in a water bath at a second preset temperature and at a second preset speed until the filler is completely dissolved;

[0073] After the filler is completely dissolved, continue to add the flavoring agent, and stir in a water bath at the third preset temperature and at the third preset speed until the flavoring agent is evenly dispersed to obtain the medicine solution.

[0074] Preferably, both the second and third preset temperatures are between 58°C and 62°C.

[0075] The second preset speed is preferably between 300 rpm and 400 rpm;

[0076] The third preset speed is preferably between 200 rpm and 300 rpm.

[0077] Step S4: Remove air bubbles from the medicine solution.

[0078] In step S4 above, degassing can be carried out in a preferred manner, for example, by one or more of the following methods: static degassing, vacuum degassing, or ultrasonic degassing.

[0079] Step S5: After degassing, the drug solution is coated, dried, and then cut to obtain sotalol hydrochloride film.

[0080] In step S5 above, the deaerated drug solution is coated, dried, and then cut to obtain a sotalol hydrochloride film. As an exemplary implementation method, it may include, for example:

[0081] Slowly pour the deaerated medicine onto the film-laying board, ensuring that the medicine evenly covers the surface of the film-laying board to a preset thickness.

[0082] The film plate, which is evenly covered with the medicine solution, is dried at the fourth preset temperature for the first preset time.

[0083] After drying, the membrane is cooled and cut to the preset size to obtain sotalol hydrochloride membrane.

[0084] Specifically, the aforementioned preset thickness is preferably between 0.8mm and 1.2mm;

[0085] The fourth preset temperature is preferably between 45℃ and 55℃;

[0086] The preferred preset time is, for example, between 50 and 70 minutes.

[0087] The preparation method of sotalol hydrochloride film in this embodiment adopts solvent casting technology. Through the process of "excipient dissolution - drug solution preparation - defoaming - film laying - drying - cutting", an oral instant film with appropriate thickness, rapid disintegration and good taste is obtained.

[0088] An embodiment of the third aspect of this application provides an oral instant-dissolving drug comprising the above-mentioned sotalol hydrochloride film, or comprising sotalol hydrochloride film prepared by the above-mentioned preparation method.

[0089] It is worth noting that, regarding the sotalol hydrochloride film for oral rapid dissolution and its preparation method in this embodiment, based on the above exemplary embodiments, the following implementation examples can be referred to in specific implementations.

[0090] Example

[0091] This example demonstrates the preparation method of sotalol hydrochloride. The specific preparation steps are as follows:

[0092] Step S1: Using an electronic balance (JJ600 type), accurately weigh 120 mg of sotalol hydrochloride raw material and place it in a clean 10 mL beaker. Solvent addition and ultrasonic dissolution: Add 5 mL of distilled water to the beaker and place the beaker in an ultrasonic cleaner (KS-150D type) until the raw material is completely dissolved, forming a clear and transparent sotalol hydrochloride aqueous solution.

[0093] Step S2: Accurately weigh 235 mg of polyvinyl alcohol (PVA 1788) and slowly add it to the sotalol hydrochloride aqueous solution prepared in step 1. Gently stir with a glass rod until the PVA is completely submerged, avoiding floating on the surface. Place the beaker at room temperature and let it stand for 30 minutes to allow the PVA to fully absorb water and swell (observe the PVA particles to expand and the solution to become slightly turbid).

[0094] Place the swollen mixture in a constant temperature water bath at 60±2℃, and turn on the magnetic stirrer (MS-A-S1010 type) at a stirring speed of 300-400 rpm. Stir continuously for 60 minutes, observing the dissolution status every 15 minutes until the PVA is completely dissolved and the solution returns to a clear and transparent state.

[0095] Step S3: Accurately weigh 120 mg of mannitol (pharmaceutical grade) and add it to the PVA-drug mixture prepared in step 2. Maintain a water bath at 60±2℃ and stir at 300-400 rpm for 15-20 minutes until the mannitol is completely dissolved (the solution has no grainy feel).

[0096] Accurately weigh 8 mg of steviol glycosides (pharmaceutical grade), add them to the above mixture, reduce the stirring speed to 200-300 rpm (to avoid generating too many bubbles), stir for 10 minutes to ensure that the steviol glycosides are evenly dispersed and without local aggregation;

[0097] Accurately weigh 10mg of blueberry flavoring (TN31195-5 type) and slowly add it dropwise to the mixture. Stir at 200-300rpm for 5 minutes to ensure even distribution of the flavoring and avoid uneven flavoring of the film due to excessively high local flavoring concentration.

[0098] Step S4: Place the beaker in a windless, room temperature environment and let it stand for 30-40 minutes to allow the air bubbles in the liquid to rise and burst naturally. After standing, shine a flashlight along the side of the liquid to observe whether there are any tiny air bubbles. If so, gently puncture them with a sterile syringe needle to ensure that there are no visible air bubbles in the liquid.

[0099] Step S5: Take a 10cm×10cm stainless steel plate, wash it, and let it air dry at room temperature; slowly pour the defoamed medicine into the center of the stainless steel plate, and use a glass rod (with tape of a certain thickness wrapped around both ends to control the film thickness) to make the medicine evenly cover the entire surface of the stainless steel plate; the thickness is about 0.1mm.

[0100] Turn on the electric heating drying oven, set the temperature to 50℃, and preheat for 30 minutes;

[0101] Place the stainless steel plate with the prepared medicine solution evenly into the middle layer of the drying oven (avoid contact with the oven wall), close the oven door, maintain the temperature at 50℃, and dry for 60 minutes (do not open the oven door during the drying process to prevent the film from shrinking and breaking due to sudden temperature changes).

[0102] After drying is complete, turn off the power to the drying oven. Once the temperature inside the oven has dropped to room temperature, remove the stainless steel plate (it must be placed stably during the cooling process to avoid tilting the stainless steel plate and causing the film to deform).

[0103] Gently cut along the edge of the film with a sterile scalpel, hold one corner of the film with tweezers, and slowly and evenly peel it off;

[0104] The peeled-off complete film is laid flat on a clean glass plate and cut into 2×2cm² film pieces to obtain sotalol hydrochloride film.

[0105] Verification Example

[0106] This validation example examines the appearance, dimensions and thickness, physical state, and key drug indicators of the sotalol hydrochloride film prepared in this example to determine that the sotalol hydrochloride film is superior to existing dosage forms.

[0107] The test results for the sotalol hydrochloride film in this example are as follows:

[0108] Appearance: The film is transparent light pink, with a smooth and flat surface, free of visible impurities or bubbles.

[0109] Size and thickness: Standard size 2cm × 2cm, thickness 0.09-0.11mm (preferably 0.10mm). Use a digital caliper to measure the thickness of the film at the four corners and the center point, measuring three times at each location and taking the average value to ensure thickness uniformity RSD ≤ 5%.

[0110] Physical state: It is a solid film at room temperature with good flexibility, can withstand more than 300 folds, and has no breakage or cracks after being folded 180°.

[0111] Table 1 Key performance testing methods and results

[0112]

[0113] It is worth noting that the drug dissolution determination in Table 1 refers to the oral film dissolution determination method (paddle method) in the Chinese Pharmacopoeia, and supplements "dissolution medium (pH 6.8 phosphate buffer 900mL), rotation speed (50rpm), sampling time points (5, 10, 15, 30min)" to clarify the standard that "dissolution rate should be ≥85% within 30min" and verify the drug release rate.

[0114] As demonstrated by the above verification examples and cases, the sotalol hydrochloride film formulation of this application can rapidly disintegrate in saliva (verification examples show that disintegration time is controlled within 30 seconds). The active ingredient is rapidly released in molecular form and acts directly on the oral mucosa. The oral mucosa is rich in capillaries and permeability channels, allowing drug molecules to rapidly penetrate the mucosal barrier and enter the bloodstream through a dual mechanism of passive diffusion and active transport. This avoids dissolution and degradation by gastrointestinal digestive juices, not only preventing direct contact between the drug and the gastrointestinal mucosa but also reducing the damage to the drug components caused by gastric acid, further improving the bioavailability of the drug.

[0115] Meanwhile, it enables precise and controllable dosage. Traditional tablets often require splitting to control dosage, but manual splitting can easily lead to dosage deviations, and the irregular edges of the split tablets may affect the drug dissolution rate and absorption. The sotalol hydrochloride film of this application is prepared using a fixed specification (2×2cm²), with each film containing 10mg of sotalol hydrochloride. The film has a uniform texture and thickness, and the drug components are uniformly dispersed within the film. In clinical application, it can be precisely cut according to the child's weight (dosage is calculated based on weight) using a special cutting tool. For example, if a child weighing 10kg needs a 5mg dose, only half a tablet (12cm²) needs to be cut. The cut film still maintains the uniformity of drug content, and the dosage deviation rate can be controlled within 5%, which is far superior to the splitting effect of traditional tablets. In addition, the standardized production process of the film also ensures the dosage consistency of each batch of products, providing a stable and reliable guarantee for individualized medication for children.

[0116] Furthermore, patient compliance is significantly better than existing technologies. For pediatric patients requiring long-term medication, the pain points of traditional dosage forms often lead to decreased compliance. The sotalol hydrochloride film formulation of this application is optimized in terms of both taste and usage scenarios, greatly improving patient acceptance: In terms of taste design, the addition of the natural flavoring agent steviol glycosides effectively masks the bitterness and irritation of the drug itself, giving the film a mild and sweet taste upon ingestion, significantly improving acceptance among pediatric patients.

[0117] In terms of usage scenarios, the film-form is small in size (2×2cm², only about 1 / 3 the size of a regular postage stamp), requiring no water to take. It disintegrates and is absorbed quickly simply by being placed on the tongue, making it convenient for administration in non-medical settings such as home, school, and travel. This completely solves the limitations of injectable medications, which "rely on professional medical personnel for administration and require use in medical institutions," and also avoids the problem of missed doses caused by the inconvenience of taking tablets with water. For infants and young children whose swallowing function is not yet fully developed, the film-form can be mixed with a small amount of breast milk or complementary food before administration, further expanding the range of users and providing more flexible options for the treatment of special populations.

[0118] The above descriptions are merely some embodiments of this application and are not intended to limit this application. The technical features or structures in the foregoing different embodiments can be arbitrarily combined to form other specific technical solutions as needed. For those skilled in the art, this application can have various modifications and variations. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of this application should be included within the scope of protection of the claims of this application.

Claims

1. A sotalol hydrochloride film formulation for rapid oral administration, characterized in that: The components of the sotalol hydrochloride film include: sotalol hydrochloride, film-forming material, filler, and flavoring agent; The film-forming material is any one or more of hydroxypropyl methylcellulose, polyvinyl alcohol, pullulan, povidone, sodium carboxymethyl cellulose, or hydroxypropyl cellulose; and / or, The filler is mannitol; and / or, The flavoring agent includes flavoring agent A and flavoring agent B, wherein flavoring agent A is any one or more of steviol glycosides, sucralose, or aspartame; and / or, The flavoring agent B is any one or more of blueberry flavoring, menthol, strawberry flavoring, or orange flavoring.

2. The sotalol hydrochloride film-forming agent according to claim 1, characterized in that: The mass ratio of sotalol hydrochloride to the film-forming material, the filler, the flavoring agent A, and the flavoring agent B is between (110-130):(220-250):(100-140):(6-10):(8-12).

3. A method for preparing a sotalol hydrochloride film, characterized in that, The preparation method includes: Sotalol hydrochloride was dissolved in a solvent to prepare a solution of the active pharmaceutical ingredient; The film-forming material is added to the raw drug solution, swollen, and then heated to dissolve, thus obtaining a mixed drug solution. The filler and flavoring agent are added sequentially to the mixed medicinal solution and dissolved to obtain the medicinal solution; Degas the medicinal solution; The deaerated drug solution is coated, dried, and then cut to obtain the sotalol hydrochloride film.

4. The method for preparing sotalol hydrochloride film according to claim 3, characterized in that, The step of adding the film-forming material to the active pharmaceutical ingredient solution, performing a swelling treatment, and then heating to dissolve it to obtain a mixed pharmaceutical solution includes: The film-forming material is slowly added to the drug substance solution and stirred until it is completely submerged. After immersion, the mixture is allowed to stand until the film-forming material swells. Then, it is placed in a water bath at a first preset temperature and stirred at a first preset speed until the film-forming material is completely dissolved, thus obtaining the mixed drug solution.

5. The method for preparing sotalol hydrochloride film according to claim 4, characterized in that: The first preset temperature is between 58℃ and 62℃; The first preset speed is between 300 rpm and 400 rpm.

6. The method for preparing sotalol hydrochloride film according to claim 3, characterized in that, The step of adding fillers and flavoring agents sequentially to the mixed medicinal solution to dissolve them, thereby obtaining the medicinal solution, includes: The filler is added to the mixed solution, and the solution is stirred in a water bath at a second preset temperature and at a second preset speed until the filler is completely dissolved. After the filler is completely dissolved, the flavoring agent is added, and the mixture is stirred in a water bath at a third preset temperature and at a third preset speed until the flavoring agent is evenly dispersed to obtain the medicine solution.

7. The method for preparing sotalol hydrochloride film according to claim 6, characterized in that: Both the second preset temperature and the third preset temperature are between 58℃ and 62℃; The second preset speed is between 300 rpm and 400 rpm; The third preset speed is between 200 rpm and 300 rpm.

8. The method for preparing sotalol hydrochloride film according to claim 3, characterized in that, The process of preparing the sotalol hydrochloride film by coating, drying, and cutting the deaerated drug solution includes: Slowly pour the deaerated medicine onto the film-laying plate, and make the medicine evenly cover the surface of the film-laying plate to a preset thickness; The film-coating plate, which is uniformly covered with the medicinal liquid, is dried at a fourth preset temperature for a first preset time. After drying, the membrane is cooled and cut to a preset size to obtain the sotalol hydrochloride membrane.

9. The method for preparing sotalol hydrochloride film according to claim 8, characterized in that: The preset thickness is between 0.8mm and 1.2mm; The fourth preset temperature is between 45℃ and 55℃; The first preset time is between 50 min and 70 min.

10. An oral fast-dissolving drug, characterized in that: The oral instant-dissolving drug includes the sotalol hydrochloride film as described in claim 1 or 2, or the oral instant-dissolving drug includes the sotalol hydrochloride film prepared by any one of the preparation methods of claims 3 to 9.

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