Medicinal marshmallow preparation and preparation method thereof

Abstract

The invention relates to a medicinal marshmallow preparation and a preparation method thereof, in particular to the technical field of biomedical materials. The medicinal marshmallow preparation comprises a marshmallow silk substrate, the medicinal active ingredients are dispersed inside and / or on the surface of the cotton candy silk substrate; wherein the cotton candy silk substrate loaded with the medicine forms an independent medicine loading unit and is sealed in a package. The invention provides a medicinal marshmallow preparation. The problems that in the prior art, due to the fact that traditional child medicine dosage forms are poor in taste, child patient medication compliance is poor, an existing candy carrier is not suitable for thermosensitive medicine due to the fact that high temperature is involved in the preparation process, and a conventional dose division mode is difficult to achieve administration accuracy and dose uniformity while palatability is guaranteed are solved.

Description

Technical Field

[0001] This application relates to the field of biomedical materials technology, and in particular to a pharmaceutical cotton candy formulation and its preparation method. Background Technology

[0002] Due to their physiological and psychological characteristics, pediatric patients generally face severe challenges in drug treatment, including difficulty swallowing and poor medication adherence. Conventional tablets and capsules are difficult to swallow, and the unpleasant taste of the medication itself (especially bitterness) is more likely to cause resistance and refusal to take it in children, directly affecting the treatment effect and the disease recovery process.

[0003] To improve children's medication experience, various flavoring formulations have been developed, such as syrups, chewable tablets, orally disintegrating tablets, and candies like gummies and lollipops. However, these formulations have significant limitations in application: First, for drugs with strong bitter tastes, conventional taste-masking techniques often fail to completely mask the flavor, and the unpleasant taste can still be perceived during administration; second, some formulations themselves (such as the viscosity of syrups and the texture of chewable tablets) are not acceptable to all children; third, the preparation of many candy carriers requires high-temperature processes, which are unsuitable for heat-sensitive drugs such as probiotics; and finally, ensuring the accuracy and uniformity of the drug dosage in each individual unit (such as a single gummy) remains a technical challenge.

[0004] Marshmallows, a popular treat among children, possess the potential to be ideal drug carriers due to their unique fluffy, fibrous structure, melt-in-your-mouth texture, and highly effective flavor masking ability. However, a mature and reliable solution for developing existing marshmallow filaments as a professional drug delivery system is still lacking. Current technologies have failed to systematically address the core issue of how to stably and uniformly load precisely measured doses of drug into a fragile filament network at room temperature, ensuring structural stability and accurate dosage during storage and administration. Therefore, a novel formulation is urgently needed to overcome these shortcomings. Summary of the Invention

[0005] This application provides a pharmaceutical marshmallow formulation and its preparation method to solve the problems in related technologies, such as poor medication compliance in children due to unpleasant taste of traditional children's drug dosage forms, unsuitability of existing candy carriers for heat-sensitive drugs due to the high temperature involved in the preparation process, and difficulty in achieving accurate and uniform dosage while ensuring palatability using conventional dispensing methods.

[0006] In a first aspect, this application provides a pharmaceutical cotton candy formulation, the pharmaceutical cotton candy formulation comprising: Marshmallow filament base; A pharmaceutically active ingredient, wherein the pharmaceutically active ingredient is dispersed within and / or on the surface of the marshmallow filament substrate; The drug-loaded cotton candy filament substrate constitutes an independent drug-carrying unit and is sealed within the packaging.

[0007] The pharmaceutical marshmallow formulation provided in this application disperses the active pharmaceutical ingredient within and / or on the surface of a marshmallow filament substrate, forming independent drug-carrying units sealed within the packaging. On one hand, the unique fluffy texture, high sweetness, and snack-like properties of marshmallows enhance children's acceptance of medication, significantly improving medication adherence. On the other hand, the strong sweetness and rapid dissolution of marshmallows effectively mask the bitterness or off-flavors of the medication, achieving excellent taste masking. Furthermore, since the medication is dispersed only after the marshmallow filaments are formed, the risk of high-temperature degradation during the preparation process is avoided, making this pharmaceutical marshmallow formulation suitable for heat-sensitive drugs. Moreover, the precise dosage and post-encapsulation method allow for more flexible and accurate adjustment of the drug content in each dosage unit based on the child's weight or treatment needs, achieving dosage flexibility. Finally, the independent, sealed packaging ensures product stability, forming a pediatric drug delivery system that combines good palatability, dosage accuracy, and storage stability.

[0008] In some embodiments, the mass ratio of the marshmallow filament substrate to the pharmaceutical active ingredient is (5-200):1.

[0009] In some embodiments, the particle size of the pharmaceutically active ingredient is less than 50 μm. Limiting the particle size of the pharmaceutically active ingredient allows it to be controlled at a specific micropowder or microparticle scale, ensuring that the pharmaceutically active ingredient can be effectively encapsulated, embedded, or attached to the interior or surface of the fluffy cotton candy filament matrix, thereby achieving uniform dispersion of the pharmaceutically active ingredient.

[0010] In some embodiments, the pharmaceutically active ingredient includes a heat-sensitive drug. Many confectionery drug carriers involve high temperatures during preparation, making them unsuitable for heat-sensitive drugs. This application avoids the risk of high-temperature degradation of the pharmaceutically active ingredient during preparation by dispersing it only after the cotton candy filaments have formed. This not only makes heat-sensitive drugs applicable but also broadens their application range, ensuring the chemical stability and biological activity of such drugs in the formulation, thus providing a new pediatric administration method that effectively protects the drug components while maintaining good palatability.

[0011] In some embodiments, the heat-sensitive drug includes at least one of acetaminophen, ibuprofen, antibiotics, vitamins, digestive enzymes, traditional Chinese medicine preparations containing volatile oils, thyroid hormones, and probiotics.

[0012] In some embodiments, the raw material components of the marshmallow filaments include sucrose. By limiting the raw material components of the marshmallow filaments to sucrose, on the one hand, the strong sweetness of sucrose, combined with the rapid dissolving characteristic of marshmallows, can effectively mask the bitterness or off-flavor of the medication, thereby achieving an excellent taste masking effect; on the other hand, the marshmallow filament matrix made from sucrose has a unique fluffy texture and a melt-in-your-mouth feel, which can improve children's acceptance of the medication and thus improve children's medication adherence.

[0013] In some embodiments, the raw material components of the marshmallow filaments also include sugar alcohols. By adding sugar alcohols to the raw material components of the marshmallow filaments, if it is desired to improve softness and stringiness, 10-20% glucose syrup or invert sugar can be added to the sucrose; if it is desired to reduce calories or extend shelf life, 30-50% isomaltose or fructooligosaccharides can be used to replace part of the sucrose, while retaining a small amount of sucrose to maintain basic sweetness and viscosity; if a special flavor is required, honey or maple syrup not exceeding 10% of the total sugar content can be added to introduce natural caramel or woody aromas; if it is made or used in a high-temperature environment, it is recommended to use maltose syrup or isomaltose to enhance the heat resistance of the filaments and prevent them from softening too quickly in the hands. In some embodiments, the sugar alcohol includes at least one of glucose syrup, isomaltitol, fructooligosaccharides, steviol glycosides, and xylitol.

[0014] In some embodiments, the pharmaceutical marshmallow formulation further includes at least one of a binder, stabilizer, moisture-proofing agent, antioxidant, flavoring agent, and coloring agent. By adding at least one of these components to the pharmaceutical marshmallow formulation, the binder enhances the adhesion between the active pharmaceutical ingredient and the marshmallow strands, thereby improving the physical stability of the formulation. The addition of stabilizers, moisture-proofing agents, and antioxidants enhances product stability. Simultaneously, the introduction of flavoring agents and coloring agents further enhances the product's appeal, combining with the excellent flavor-masking effect of the marshmallow itself to improve children's medication adherence. The comprehensive application of these excipients can solve problems such as insufficient drug adhesion, easy spoilage during storage, and limited acceptance by children, thereby optimizing the formulation's stability, safety, and palatability.

[0015] In some embodiments, the adhesive includes at least one of PVP, HPMC, corn starch paste, and gum arabic aqueous solution.

[0016] In some embodiments, the desiccant includes at least one of silica gel microparticles and molecular sieves.

[0017] In some embodiments, the antioxidant includes vitamin C.

[0018] In some embodiments, the packaging is an independent sealed unit filled with inert gas and / or containing a desiccant. By using nitrogen-filled packaging and / or adding pharmaceutical-grade desiccants, moisture and oxygen can be further isolated, extending shelf life and ensuring that the product maintains its physical structure and does not harden or degrade its drug content during storage and transportation, thereby ensuring product stability.

[0019] Secondly, this application provides a method for preparing the above-mentioned pharmaceutical cotton candy formulation, comprising the following steps: S1. Prepare the cotton candy filament substrate; S2. In an environment with a relative humidity of 10-40% and a temperature of 10-30℃, the pharmaceutical active ingredients are dispersed in the interior and / or surface of the cotton candy filament substrate to form a drug-loaded unit. S3. The drug delivery unit is packaged independently.

[0020] The preparation method provided in this application involves first forming a marshmallow filament substrate under conventional conditions, then dispersing precisely measured pharmaceutical active ingredients within and / or onto the substrate in a strictly controlled low-humidity and room-temperature environment, and finally individually sealing and packaging them. This method completely separates the drug loading step from the high-temperature preparation process of the marshmallow matrix, effectively avoiding the degradation risks that heat-sensitive drugs may encounter during production. Furthermore, the post-processing dispersion technique and controlled environment ensure the uniformity of drug distribution, the accuracy of dosage, and the physical stability of the product. This process is simple, efficient, and operates under mild and controllable conditions.

[0021] In some embodiments, in step S2, the dispersion process includes at least one of fluidized bed spraying, powder deposition, electrostatic adsorption, blending granulation, and physical placement. The above methods can complete drug loading at room temperature or under mild conditions, effectively avoiding the risk of high-temperature degradation of the drug during preparation, and are suitable for heat-sensitive drugs.

[0022] In some embodiments, step S2 further includes applying an adhesive to the drug-loaded marshmallow filament substrate. Applying the adhesive after step S2 enhances the bonding strength between the drug particles and the marshmallow filament substrate.

[0023] In some embodiments, step S2 further includes: using an online quality detection system to monitor and control the drug content in the drug-loading unit in real time. By introducing an online quality detection system in step S2 to monitor and control the drug content in real time, it is possible to quickly detect the drug content and distribution of each batch of drug-loaded cotton candy during the production process, thereby ensuring that the dosage uniformity of the final product meets pharmacopoeia standards.

[0024] Compared with existing technologies, the beneficial effects of this application are: 1. By utilizing the inherent fluffy, fibrous structure, high sweetness, and appealing nature of marshmallows as a snack, children's resistance to traditional medications can be eliminated. Their potent sweetness and melt-in-your-mouth properties create sensory masking before the medication reaches the taste buds, effectively masking unpleasant tastes (such as bitterness) and greatly improving children's acceptance of medication.

[0025] 2. This formulation employs a unique post-loading drug delivery process, where the drug is loaded into pre-made marshmallow filaments at room temperature. This completely avoids the high-temperature steps involved in traditional confectionery preparation, allowing for the safe application of heat-sensitive drugs (such as certain probiotics and antibiotics). Furthermore, based on precise post-loading metrology technology, the drug content of each individual unit can be flexibly and accurately adjusted according to individualized treatment needs, achieving precise dose distribution.

[0026] 3. The drug delivery unit is monitored and controlled in real time through an online quality inspection system. Combined with independent, sealed, and moisture-proof packaging in a strictly controlled low-humidity, clean environment, the high uniformity of drug content in each formulation unit and the physical and chemical stability of the product during storage are ensured.

[0027] 4. This invention is the first to systematically develop marshmallow filaments as a drug delivery carrier, and its unique morphology and delivery method are novel and inventive. Furthermore, the rapid dissolution of marshmallows in the oral cavity facilitates rapid drug release, potentially offering the advantage of rapid onset of action. Attached Figure Description

[0028] To more clearly illustrate the technical solutions in the embodiments of this application, the accompanying drawings used in the description of the embodiments will be briefly introduced below. Obviously, the accompanying drawings described below are only some embodiments of this application. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0029] Figure 1 This is a flowchart of the preparation method of the pharmaceutical cotton candy formulation of this application. Detailed Implementation

[0030] To make the objectives, technical solutions, and advantages of this application clearer, the technical solutions of this application will be clearly and completely described below in conjunction with the embodiments of this application. Obviously, the described embodiments are only some, not all, of the embodiments of this application. Based on the embodiments of this application, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of this application.

[0031] Children face numerous challenges in taking medication due to their physiological characteristics and psychological factors. Common problems include: bitter taste of medication, difficulty swallowing, and resistance to tablets or capsules, leading to poor compliance, missed doses, or refusal to take medication, which seriously affects treatment effectiveness.

[0032] Currently, to improve children's medication adherence, various flavor-adjustable and easy-to-take dosage forms have been developed, such as syrups, chewable tablets, orally disintegrating tablets, gummies, and lollipops. However, these dosage forms still have limitations: (1) Insufficient flavor masking: Some drugs have a very strong bitter or unpleasant taste, which is difficult to completely mask with existing dosage forms.

[0033] (2) Dosage form limitations: Some children still reject the taste of chewable tablets or syrups and have limited acceptance of irregularly shaped candy dosage forms.

[0034] (3) Not applicable to heat-sensitive drugs: The preparation process of many confectionery drug carriers involves high temperatures, which is not applicable to heat-sensitive drugs.

[0035] (4) Dosage accuracy challenge: Some drugs that require precise dosage are difficult to adjust flexibly in traditional candy formulations.

[0036] Marshmallows, a popular dessert among children, are highly appealing due to their unique fluffy texture, melt-in-your-mouth taste, and high sweetness. However, to date, there has been little systematic development and application of using pre-formed marshmallow strands as drug carriers, specifically addressing dosage uniformity, stability, and palatability for pediatric medications. In particular, existing technologies lack mature and reliable solutions for preventing drug degradation at high temperatures and achieving precise drug encapsulation and stable retention.

[0037] In view of this, this application provides a pharmaceutical marshmallow formulation and its preparation method to solve the problems in related technologies, such as poor medication compliance in children due to unpleasant taste of traditional children's drug dosage forms, unsuitability of existing candy carriers for heat-sensitive drugs due to the high temperature involved in the preparation process, and difficulty in achieving accurate and uniform dosage while ensuring palatability using conventional dispensing methods.

[0038] In a first aspect, this application provides a pharmaceutical cotton candy formulation, the pharmaceutical cotton candy formulation comprising: Marshmallow filament base; A pharmaceutically active ingredient, wherein the pharmaceutically active ingredient is dispersed within and / or on the surface of the marshmallow filament substrate; The drug-loaded cotton candy filament substrate constitutes an independent drug-carrying unit and is sealed within the packaging.

[0039] The pharmaceutical marshmallow formulation provided in this application disperses the active pharmaceutical ingredient within and / or on the surface of a marshmallow filament substrate, forming independent drug-carrying units sealed within the packaging. On one hand, the unique fluffy texture, high sweetness, and snack-like properties of marshmallows enhance children's acceptance of medication, significantly improving medication adherence. On the other hand, the strong sweetness and rapid dissolution of marshmallows effectively mask the bitterness or off-flavors of the medication, achieving excellent taste masking. Furthermore, since the medication is dispersed only after the marshmallow filaments are formed, the risk of high-temperature degradation during the preparation process is avoided, making this pharmaceutical marshmallow formulation suitable for heat-sensitive drugs. Moreover, the precise dosage and post-encapsulation method allow for more flexible and accurate adjustment of the drug content in each dosage unit based on the child's weight or treatment needs, achieving dosage flexibility. Finally, the independent, sealed packaging ensures product stability, forming a pediatric drug delivery system that combines good palatability, dosage accuracy, and storage stability.

[0040] In some embodiments provided in this application, the mass ratio of the cotton candy filament substrate to the pharmaceutical active ingredient is (5-200):1.

[0041] In some embodiments provided in this application, the particle size of the pharmaceutically active ingredient is less than 50 μm. Limiting the particle size of the pharmaceutically active ingredient allows it to be controlled at a specific micro-powder or microparticle scale, ensuring that the pharmaceutically active ingredient can be effectively encapsulated, embedded, or attached to the interior or surface of the fluffy cotton candy filament matrix, thereby achieving uniform dispersion of the pharmaceutically active ingredient.

[0042] In some embodiments provided in this application, the pharmaceutically active ingredient includes heat-sensitive drugs. Many confectionery drug carriers involve high temperatures during preparation, making them unsuitable for heat-sensitive drugs. This application, however, avoids the risk of high-temperature degradation of the pharmaceutically active ingredient during preparation by dispersing it only after the cotton candy filaments have formed. This not only makes heat-sensitive drugs applicable but also broadens their application scope, ensuring the chemical stability and biological activity of such drugs in formulations. Therefore, it provides a new pediatric administration method that effectively protects the drug components while maintaining good palatability.

[0043] There is no particular limitation on the types of heat-sensitive drugs, and those skilled in the art can choose flexibly as needed. The heat-sensitive drugs include, but are not limited to, at least one of acetaminophen, ibuprofen, antibiotics, vitamins, digestive enzymes, traditional Chinese medicine preparations containing volatile oils, thyroid hormones, and probiotics.

[0044] In some embodiments provided in this application, the raw material components of the marshmallow filaments include sucrose. By limiting the raw material components of the marshmallow filaments to sucrose, on the one hand, sucrose, as the main component, with its strong sweetness combined with the rapid dissolving characteristics of marshmallows, can effectively mask the bitterness or off-flavor of the drug, thereby achieving an excellent taste masking effect; on the other hand, the marshmallow filament matrix made from sucrose has a unique fluffy texture and a melt-in-your-mouth mouthfeel, thereby increasing children's acceptance of the drug and thus improving children's medication adherence.

[0045] In some embodiments provided in this application, to optimize the structure and texture of the marshmallow filaments, specific sugar alcohols are added to the basic sugars (such as sucrose). These substances have better fluidity and thermal stability after being heated and melted. After being ejected through a high-speed rotating nozzle, they can cool and solidify more quickly into fine, uniform glassy fibers, thereby forming a more stable, less hygroscopic, and appropriately sweet marshmallow filament skeleton.

[0046] Furthermore, to improve softness and stringiness, 10-20% glucose syrup or invert sugar can be added to the sucrose; to reduce calories or extend shelf life, 30-50% isomalutose or fructooligosaccharides can be used to replace part of the sucrose, while retaining a small amount of sucrose to maintain basic sweetness and viscosity; to impart special flavor, honey or maple syrup of no more than 10% of the total sugar can be added to introduce natural caramel or woody aromas; if made or used in a high-temperature environment (such as for live performances), it is recommended to use maltose syrup or isomalutose to enhance the heat resistance of the sugar strands and prevent them from softening too quickly in the hands.

[0047] The type of sugar alcohol is not specifically limited, and those skilled in the art can choose flexibly as needed. The sugar alcohol is pharmaceutical grade, including but not limited to glucose syrup, isomalt, fructooligosaccharides, and natural high-intensity sweeteners such as steviol glycosides and xylitol. These components can be used in combination with sucrose to improve processing performance and final product quality through synergistic effects.

[0048] In some embodiments provided in this application, the pharmaceutical marshmallow formulation further includes at least one of a binder, stabilizer, moisture-proofing agent, antioxidant, flavoring agent, and coloring agent. By adding at least one of these components to the pharmaceutical marshmallow formulation, the binder enhances the adhesion between the active pharmaceutical ingredient and the marshmallow strands, thereby improving the physical stability of the pharmaceutical marshmallow formulation. The addition of stabilizers, moisture-proofing agents, and antioxidants enhances product stability. Simultaneously, the introduction of flavoring agents and coloring agents further enhances the product's appeal, combining with the excellent flavor-masking effect of the marshmallow itself to improve children's medication adherence. The comprehensive application of these excipients can solve problems such as insufficient drug adhesion, easy spoilage during storage, and limited acceptance by children, thereby optimizing the formulation's stability, safety, and palatability.

[0049] As an example, the adhesive includes at least one of PVP, HPMC, corn starch paste, and gum arabic aqueous solution.

[0050] As an example, the desiccant includes at least one of silica gel microparticles and molecular sieves.

[0051] As an example, the antioxidants include vitamin C.

[0052] In some embodiments provided in this application, the packaging is an independent sealed unit filled with inert gas and / or containing a desiccant. By using nitrogen-filled packaging and / or adding pharmaceutical-grade desiccants, moisture and oxygen can be further isolated, extending the shelf life and ensuring that the product maintains its physical structure and does not harden or degrade its drug content during storage and transportation, thereby ensuring product stability.

[0053] Secondly, this application provides a method for preparing the above-mentioned pharmaceutical cotton candy formulation, comprising the following steps: Step S1: Prepare the cotton candy filament substrate; This step aims to prepare the marshmallow filament base. Specifically, sucrose (and / or other pharmaceutical-grade sugar alcohols or sugars) is heated and melted to a suitable temperature (approximately 150-160°C). The molten sugar solution is then centrifuged using a GMP-compliant marshmallow machine, rapidly cooled and solidified in air, forming long, fluffy marshmallow filaments, which are then collected into marshmallow filament bundles of predetermined size and weight. The entire preparation process should be carried out in a strictly controlled environment (low humidity) and cleanliness.

[0054] Step S2: In an environment with a relative humidity of 10-40% and a temperature of 10-30℃, the pharmaceutical active ingredients are dispersed in the interior and / or surface of the cotton candy filament substrate to form a drug-loaded unit. In this step, in an environment where temperature and relative humidity are controlled, a drug-loaded unit is formed by uniformly dispersing the pharmaceutical active ingredient inside and / or on the surface of the marshmallow filament substrate.

[0055] Furthermore, in step S2, the dispersion process includes at least one of directional spraying / electrostatic deposition, mechanical embedding / sandwiching, and pre-formulation combination. Through methods such as directional spraying / electrostatic deposition, mechanical embedding / sandwiching, or pre-formulation combination, a predetermined dose of the pharmaceutical active ingredient is uniformly dispersed and fixed within and / or onto the surface of the cotton candy filament substrate. This method ensures the dosage uniformity and stability of the pharmaceutical active ingredient. Spraying and electrostatic deposition methods achieve highly uniform drug distribution within the filament structure and can be enhanced with adhesive spraying to improve adhesion. Mechanical embedding / sandwiching physically encapsulates the pharmaceutical active ingredient within the filament mesh. Pre-formulation combination further protects the drug through coating, microencapsulation, etc., and may improve controlled release characteristics and dosage uniformity.

[0056] Specifically, the directional spray / electrostatic deposition method involves micronizing a predetermined dose of the pharmaceutical active ingredient and dispersing it in an inert gas or preparing a suspension. The prepared marshmallow filaments are placed in a sealed chamber or a specific workstation. Using a precisely controlled spray device or electrostatic spray gun, the drug micronization is uniformly sprayed or electrostatically deposited onto the surface and internal structure of the marshmallow filaments. During this process, the marshmallow filaments can be slowly rotated or tumbled to ensure uniform drug distribution. Subsequently, a trace amount of pharmaceutical-grade adhesive solution can be selectively sprayed to increase drug adhesion, followed by immediate rapid drying (e.g., cold air drying, vacuum drying).

[0057] Mechanical embedding / sandwich method: First, accurately weigh a portion of drug powder or fragments, then divide the predetermined weight of marshmallow filaments into two or more layers; next, evenly distribute the precisely measured amount of drug between the marshmallow filament layers; finally, carefully close the layers of marshmallow filaments and gently press them together, so that the drug particles are physically encapsulated within the marshmallow filament network. This method may be suitable for drugs with larger particles or requiring less precise distribution.

[0058] Drug preformulation binding method: The active pharmaceutical ingredient is pre-prepared into preformed particles in the form of coatings, microcapsules, or microspheres to enhance its stability and controlled release; these preformed particles are then gently mixed with cotton candy filaments in a specific device, or bound to the cotton candy after it has been formed using the aforementioned spray or embedding techniques. This method is beneficial for further protecting the drug and may improve dosage uniformity.

[0059] In some embodiments provided in this application, step S2 is followed by applying an adhesive to the drug-loaded marshmallow filament substrate. Applying the adhesive after step S2 enhances the bonding strength between the drug particles and the marshmallow filament substrate.

[0060] S3, The drug delivery unit is packaged independently.

[0061] In this step, the drug delivery unit is individually packaged to isolate it from the external environment and ensure product stability.

[0062] Furthermore, to ensure product stability, the entire process from cotton candy production to drug encapsulation should be carried out in a low-humidity, constant-temperature, and highly clean environment to prevent the cotton candy from absorbing moisture and becoming contaminated by microorganisms. Based on this, individual sealed packaging is crucial for ensuring product stability; each dose unit of the drug cotton candy formulation should be immediately sealed in an airtight, moisture-proof, and light-proof individual package (such as blister packs or sealed bags) made of multi-layer composite materials (such as aluminum-plastic composite film). In addition, pharmaceutical-grade desiccants (such as silica gel pouches) can be selectively added to the packaging, or nitrogen-filled packaging can be used to further isolate moisture and oxygen, thereby extending the product's shelf life.

[0063] In some embodiments provided in this application, step S2 further includes: using an online quality detection system to monitor and control the drug content in the drug-loading unit in real time. By introducing an online quality detection system in step S2 to monitor and control the drug content in real time, it is possible to quickly detect the drug content and distribution of each batch of drug-loaded cotton candy during the production process, thereby ensuring that the dosage uniformity of the final product meets pharmacopoeia standards.

[0064] Specifically, to control the dosage uniformity and drug retention of the product, the following measures are taken: An automated metering system consisting of high-precision sensors and automated robotic arms is used to precisely control the weight of each cotton candy ball and the amount of drug encapsulated within it; after the encapsulation process, near-infrared (NIR) spectroscopy, Raman spectroscopy, or other image recognition technologies can be introduced to rapidly detect the drug content and distribution of each cotton candy formulation online, ensuring that the dosage uniformity meets pharmacopoeia standards; in addition, by conducting tests on the formulation under simulated transportation and storage conditions, including vibration, drop, and friction, and combining this with drug content analysis, the extent to which the drug detaches or is lost from the cotton candy fibers is assessed, and the encapsulation process or excipients can be adjusted as needed.

[0065] Furthermore, rigorous quality control is implemented on the final product, specifically including: drug content determination to ensure that the API content in each formulation meets the labeled amount; dose uniformity testing to assess the difference in drug content between dosage units according to pharmacopoeia standards; physical stability to examine the physical form of the marshmallow (whether it melts or clumps), adhesiveness, and drug shedding under storage conditions (such as accelerated stability testing); chemical stability to determine the degradation products and content changes of the drug during storage; in vitro dissolution or release rate to evaluate the rate and extent of drug release from the marshmallow formulation; microbial limit testing to ensure that the product meets microbiological requirements; and taste evaluation to assess the taste masking effect through in vitro or human (adult volunteer) taste tests.

[0066] The technical solutions provided in this application will be described in detail below with reference to the embodiments.

[0067] Example 1 Example 1 of this application provides a pharmaceutical cotton candy preparation. This example uses acetaminophen as an example to specifically illustrate its implementation as a pediatric antipyretic and analgesic drug in the cotton candy preparation: Formula: Marshmallow filament base (100% pharmaceutical grade sucrose, 5.0g / serving); pharmaceutical active ingredient (acetaminophen micro powder, particle size 35μm, 40mg / serving).

[0068] 1. Preparation of sucrose marshmallows: Heat pharmaceutical grade sucrose to a suitable temperature (the first spoonful of sugar is about 180°C, and the subsequent spoonfuls are adjusted to 167±2°C). Use a food-grade marshmallow machine to throw the molten sugar liquid out using centrifugal force. The liquid is then rapidly cooled and solidified in the air to form long, fluffy marshmallow strands, which are then cut into marshmallow balls of about 5 grams each.

[0069] 2. Micronization of acetaminophen: Pharmaceutical-grade acetaminophen is micronized to control its particle size to less than 50 micrometers.

[0070] 3. Drug Encapsulation: Using a directional spray method, 50 mg of precisely weighed acetaminophen micropowder is evenly sprayed onto the surface and internal structure of the marshmallow while the marshmallow mass rotates at a constant speed of 10-15 rpm. The powder is then distributed onto the surface and internal structure of the marshmallow mass via electrostatic adsorption. Subsequently, a small amount of 0.45% w / v PVP K30 aqueous solution is sprayed as a binder using a 0.3 mm orifice nozzle at an atomization pressure of 0.2 MPa. Each application is 0.1 mL, and the mixture is immediately cooled and dried to fix the drug.

[0071] 4. Packaging: Quickly pack the prepared pharmaceutical cotton candy formulation into individual aluminum-plastic composite film sealed bags, and place a small packet of pharmaceutical-grade silica gel desiccant (about 5g) in each bag.

[0072] Example 2 Example 2 provides a pharmaceutical cotton candy preparation, similar to Example 1, and the specific experimental procedure is as follows: Formula: Marshmallow filament base (sucrose: maltitol = 6:4, 4.8g / serving); pharmaceutical active ingredient (ibuprofen micro powder, particle size 28μm, 40mg / serving).

[0073] 1. Process: Drug dispersion is achieved using a powder deposition sandwich method. A predetermined weight of marshmallow filaments is manually or mechanically cut into upper and lower layers. 40 mg of precisely weighed ibuprofen micropowder is evenly sprinkled onto the surface of the lower layer of marshmallow filaments. The upper layer of marshmallow filaments is then placed on top, and the drug particles are physically encapsulated within the marshmallow filament network by gentle rolling or compaction. Subsequently, a 1% HPMC solution is sprayed at a rate of 0.15 mL / part using a spray gun, followed by fluidized bed drying at 25°C and an air velocity of 4 m / s for 3 minutes.

[0074] 2. Packaging: Individually packaged in blister packs with built-in molecular sieve desiccant.

[0075] Example 3 Example 3 provides a medicinal cotton candy preparation, similar to Example 1, and the specific experimental procedure is as follows: Formula: Based on Example 1, "In step 1, when preparing the marshmallow filament base, 0.3% vitamin C and 0.5% aspartame are pre-mixed evenly with sucrose raw materials, and then melt-drawn into filaments." Process: The drug is loaded using electrostatic adsorption and integrated with a near-infrared (NIR) online detection system for real-time monitoring and feedback control of drug content. An NIR probe is installed behind the drug loading station to quickly scan each drug loading unit. The spectral data is compared with a pre-established content model. If the detected value deviates from the set range (40±2mg), the system automatically adjusts the vibration frequency of the drug feeder to achieve closed-loop control.

[0076] Comparative Example 1 Comparative Example 1 provides a pharmaceutical cotton candy formulation, similar to Example 1, except for the drug loading process, which is as follows: (unstructured simple mixing) Compared with Example 1, the electrostatic adsorption and adhesive fixation steps were eliminated. A simple mechanical mixing drug loading method was adopted. 40 mg of precisely weighed acetaminophen micro powder and 5.0 g of marshmallow filaments were placed together in a sealed container and mixed by hand shaking or by a roller mixer at 20 rpm for 5 minutes to achieve a simple and random mechanical mixing of the drug and the marshmallow filaments.

[0077] Comparative Example 2 Comparative Example 2 provides a pharmaceutical cotton candy formulation, similar to Example 1, except that the particle size of the pharmaceutical active ingredient is adjusted to 120 μm and drug loading is completed in an environment with a relative humidity of 65%.

[0078] Comparative Example 3 Comparative Example 3 provides a pharmaceutical marshmallow formulation similar to Example 1, except that it does not have an adhesive and does not have individual packaging.

[0079] Performance testing Strict quality control was performed on the pharmaceutical marshmallow formulations obtained in Examples 1-3 and Comparative Examples 1-3, specifically including: drug content determination to ensure that the content of the active pharmaceutical ingredient (API) in each formulation meets the labeled amount; dose uniformity test to assess the difference in drug content between dosage units according to pharmacopoeia standards; physical stability to examine the physical form of the marshmallow (whether it melts or clumps), adhesiveness, drug shedding, etc. under storage conditions (such as accelerated stability test); chemical stability to determine the degradation products and content changes of the drug during storage; in vitro dissolution or release rate to evaluate the rate and extent of drug release from the marshmallow formulation; microbial limit test to ensure that the product meets microbiological requirements; and taste evaluation to assess the taste masking effect through in vitro or human (adult volunteer) taste tests.

[0080] The specific testing procedures and inspection indicators shall be performed in accordance with the relevant requirements for tablets in the Chinese Pharmacopoeia (2025 edition). The following explanation uses acetaminophen as an example; the inspection method for ibuprofen is the same and will not be repeated here.

[0081] Reference solutions: Accurately weigh acetaminophen standard, dissolve and quantitatively dilute it in the mobile phase to prepare solutions with concentrations of 4, 5, 6, 7, 8, 9, and 10 μg / mL. -1 The absorbance (A) of an acetaminophen solution was measured at the maximum absorption wavelength (257 nm), and a regression curve was plotted. The curve equation is: Y = 0.0626X + 0.0013, R 2 =0.9998, indicating that the concentration range is 4–10 μg·mL. -1 Within the range, there is a good linear relationship.

[0082] Preparation method of test solution: Take an appropriate amount of the prepared pharmaceutical cotton candy preparation (equivalent to 40 mg of acetaminophen), physically compress it, put it into a 250 mL volumetric flask, add 50 mL of 0.4% sodium hydroxide solution and 50 mL of water, shake to dissolve the acetaminophen, dilute with water to the mark, shake well, filter, accurately measure 5 mL of the filtrate, put it into a 100 mL volumetric flask, add 10 mL of 0.4% sodium hydroxide solution, dilute with water to the mark, and shake well.

[0083] Drug content determination and content uniformity check: Following the preparation method of the test sample solution, 10 pharmaceutical cotton candy preparations obtained in Examples 1-3 and Comparative Examples 1-3 were used to prepare test sample solutions. The average content of the 10 samples was taken as the final drug content determination result.

[0084] Take the test solution and record the content of 10 pharmaceutical cotton candy preparations from each of Examples 1-3 and Comparative Examples 1-3. Determine the relative content (x) of each single pharmaceutical cotton candy preparation with a labeled amount as 100. i Measure its mean (X), standard deviation (S), and the absolute value (A) of the difference between the labeled amount and the mean. A = |100-X|. Calculate A+2.2S. If A+2.2S≤15, then the uniformity of the content of the test sample meets the requirements.

[0085] Accelerated stability testing: Referring to the "Guidelines for Stability Testing of Raw Materials and Preparations" in the Chinese Pharmacopoeia (2025 Edition), the pharmaceutical cotton candy preparations obtained in Examples 1-3 and Comparative Examples 1-3 were placed in aluminum-plastic blister packaging and placed at a temperature of (40±2)°C and a relative humidity of (75±5)% for 3 months. Samples were taken at 0, 1, 2, and 3 months for testing (the results for 6 months were not conducted due to time constraints). The appearance, content, and related substances of the pharmaceutical cotton candy preparations were examined and compared with those on day 0.

[0086] In vitro dissolution or release rate: The dissolution and release rate determination was performed according to the Chinese Pharmacopoeia (2025 edition) (General Rule 0931, Method 1). Six pharmaceutical cotton candy preparations from Examples 1-3 and Comparative Examples 1-3 were randomly selected. Using 24 mL of dilute hydrochloric acid diluted to 1000 mL as the dissolution medium, the dissolution was performed at 100 rpm. Samples were taken after 30 minutes. An appropriate amount of the dissolution solution was taken, filtered, and an appropriate amount of the filtrate was accurately measured and quantitatively diluted with 0.04% sodium hydroxide solution to a solution containing 5-10 μg of acetaminophen per mL. The absorbance was measured at a wavelength of 257 nm using ultraviolet-visible spectrophotometry (General Rule 0401). The amount dissolved per tablet was calculated based on the absorption coefficient (E1%1cm) of C8H9NO2 being 715. This amount should be greater than 80% of the labeled amount.

[0087] Microbial limit test: Take an appropriate amount of pharmaceutical marshmallow preparation, dissolve or dilute it with a suitable buffer or culture medium to prepare a test solution. Perform the test according to the Microbial Counting Method (General Chapter 1105) and Control Bacteria Test Method (General Chapter 1106) of the Chinese Pharmacopoeia (2025 Edition) and the Microbial Limit Standard for Non-sterile Drugs (General Chapter 1107). The test result must meet the following requirement: TAMC ≤10 3 CFU / g, TYMC≤10 2 The concentration of CFU / g must be within the range of CFU / g, and Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans must not be detected.

[0088] Taste assessment: Five healthy adult volunteers were selected and rated the taste of the medicated marshmallow preparations on a scale of 0-10, rinsing their mouths with water during the process. The scores for each marshmallow preparation were recorded, and the average score was used as the final taste score.

[0089] The test results are shown in Table 1: Table 1

[0090] As shown in Table 1, compared with the test data of Comparative Examples 1-3, the drug cotton candy preparations of Examples 1-3 showed excellent performance in terms of drug content accuracy, dosage uniformity, physical and chemical stability, microbial control and flavor masking effect.

[0091] The test data from Comparative Example 1 showed that the drug content of the cotton candy preparation prepared using a simple mechanical mixing method varied significantly between batches. This result demonstrates that conventional mixing methods in the field cannot guarantee the uniformity of the final product's content.

[0092] The test data of Comparative Example 2 showed that the obtained formulation had problems such as uneven drug distribution, poor dosage accuracy, and decreased product stability.

[0093] Comparative Example 3, which did not use adhesives and was not individually sealed, showed that despite its good initial taste, its physical stability (the sugar strands melted on day 1) and chemical stability (the impurity content was substandard) deteriorated sharply, and it also failed the microbiological test.

[0094] In summary, the pharmaceutical marshmallow formulation provided in this application disperses the active pharmaceutical ingredient within and / or on the surface of a marshmallow filament substrate, forming independent drug-carrying units sealed within the packaging. On one hand, the unique fluffy texture, high sweetness, and snack-like properties of marshmallows enhance children's acceptance of medication, significantly improving medication adherence. On the other hand, the strong sweetness and rapid dissolution of marshmallows effectively mask the bitterness or off-flavors of the medication, achieving excellent taste masking. Furthermore, since the medication is dispersed only after the marshmallow filaments are formed, the risk of high-temperature degradation during the preparation process is avoided, making this pharmaceutical marshmallow formulation suitable for heat-sensitive drugs. Moreover, the precise dosage and post-encapsulation method allow for more flexible and accurate adjustment of the drug content in each dosage unit based on the child's weight or treatment needs, achieving dosage flexibility. Finally, the independent, sealed packaging ensures product stability, forming a pediatric drug delivery system that combines good palatability, dosage accuracy, and storage stability.

[0095] In the description of this specification, the references to terms such as "one embodiment / mode," "some embodiments / modes," "example," "specific example," or "some examples," etc., indicate that a specific feature, structure, material, or characteristic described in connection with that embodiment / mode or example is included in at least one embodiment / mode or example of this application. In this specification, the illustrative expressions of the above terms do not necessarily refer to the same embodiment / mode or example. Moreover, the specific features, structures, materials, or characteristics described may be combined in any suitable manner in one or more embodiments / modes or examples. Furthermore, without contradiction, those skilled in the art can combine and integrate the different embodiments / modes or examples described in this specification, as well as the features of different embodiments / modes or examples.

[0096] It should be noted that in this application, relational terms such as "first" and "second" are used merely to distinguish one entity or operation from another, and do not necessarily require or imply any such actual relationship or order between these entities or operations. Furthermore, the terms "comprising," "including," or any other variations thereof are intended to cover non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements includes not only those elements but also other elements not expressly listed, or elements inherent to such a process, method, article, or apparatus. Without further limitations, an element defined by the phrase "comprising one..." does not exclude the presence of other identical elements in the process, method, article, or apparatus that includes said element. In this application, "a plurality of" means at least two, such as two, three, etc., unless otherwise expressly specified.

[0097] The above description is merely a specific embodiment of this application, enabling those skilled in the art to understand or implement this application. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of this application. Therefore, this application is not to be limited to the embodiments shown herein, but is to be accorded the widest scope consistent with the principles and novel features claimed herein.

Claims

1. A pharmaceutical cotton candy formulation, characterized in that, include: Marshmallow filament base; A pharmaceutically active ingredient, wherein the pharmaceutically active ingredient is dispersed within and / or on the surface of the marshmallow filament substrate; The drug-loaded cotton candy filament substrate constitutes an independent drug-carrying unit and is sealed within the packaging.

2. The pharmaceutical marshmallow formulation as described in claim 1, characterized in that, The mass ratio of the cotton candy filament substrate to the pharmaceutical active ingredient is (5-200):

1.

3. The pharmaceutical marshmallow formulation as described in claim 1, characterized in that, The particle size of the pharmaceutically active ingredient is less than 50 μm; and / or, The pharmaceutically active ingredient includes heat-sensitive drugs; and / or, The heat-sensitive drugs include at least one of acetaminophen, ibuprofen, antibiotics, vitamins, digestive enzymes, traditional Chinese medicine preparations containing volatile oils, thyroid hormones, and probiotics.

4. The pharmaceutical marshmallow formulation as described in claim 1, characterized in that, The raw material components of the cotton candy filaments include sucrose.

5. The pharmaceutical marshmallow formulation as described in claim 4, characterized in that, The raw material components of the cotton candy filaments also include sugar alcohols; and / or, The sugar alcohols include at least one of glucose syrup, isomaltitol, fructooligosaccharides, steviol glycosides, and xylitol.

6. The pharmaceutical marshmallow formulation as described in claim 1, characterized in that, The pharmaceutical marshmallow formulation further includes at least one of a binder, stabilizer, moisture-proofing agent, antioxidant, flavoring agent, and coloring agent; and / or, The adhesive comprises at least one of PVP, HPMC, corn starch paste, and gum arabic aqueous solution; and / or, The moisture-proofing agent includes at least one of silica gel microparticles and molecular sieves; and / or, The antioxidants include vitamin C.

7. The pharmaceutical marshmallow formulation as described in claim 1, characterized in that, The packaging is an independent sealed unit, which is filled with inert gas and / or contains a desiccant.

8. A method for preparing a pharmaceutical marshmallow formulation as described in any one of claims 1-7, characterized in that, include: S1. Provides a marshmallow filament base; S2. In an environment with a relative humidity of 10-40% and a temperature of 10-30℃, the pharmaceutical active ingredients are dispersed in the interior and / or surface of the cotton candy filament substrate to form a drug-loaded unit. S3. The drug delivery unit is packaged independently.

9. The method as described in claim 8, characterized in that, In step S2, the dispersion process includes at least one of fluidized bed spraying, powder deposition, electrostatic adsorption, blending granulation, and physical placement; and / or, Step S2 is followed by applying an adhesive to the drug-loaded marshmallow filament substrate.

10. The method as described in claim 8, characterized in that, Step S2 also includes: using an online quality detection system to monitor and control the drug content in the drug delivery unit in real time.

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