A gaba slow-release coating powder and a preparation method and application thereof

Abstract

The application relates to the technical field of pharmaceutical preparations, in particular to a GABA slow-release coating powder as well as a preparation method and application thereof. The GABA slow-release coating powder comprises GABA powder and a coating layer. The coating layer comprises sodium alginate, a macromolecular base material, a small-molecule filler and an emulsifier in a weight ratio of 0.2-2.5:1-10:1-20:0.5-8. Through the combination of sodium alginate and specific functional components, the mechanical strength of the sodium alginate coating layer is increased, the stability of the product is improved, the slow-release effect of the small-molecule water-soluble drug GABA powder is realized, and the efficacy of the product is improved.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical formulation technology, specifically to a GABA sustained-release coating powder, its preparation method, and its application. Background Technology

[0002] Gamma-aminobutyric acid (GABA) is a major inhibitory neurotransmitter widely distributed in the central nervous system of mammals. It plays a crucial role in regulating neuronal excitability and maintaining the homeostasis of the nervous system. GABA inhibits neuronal overexcitation by binding to specific GABA receptors (such as GABAA and GABAB receptors), thus playing important physiological functions in controlling anxiety, relieving stress, improving sleep, and regulating muscle tone. GABA deficiency or dysfunction is closely related to various neurological disorders, including anxiety disorders, insomnia, epilepsy, depression, and Parkinson's disease. GABA biosynthesis is mainly completed through the decarboxylation of glutamate catalyzed by glutamate decarboxylase (GAD), while its degradation depends on the action of GABA transaminase (GABA-T). The metabolic pathway of GABA plays a key role in maintaining its physiological concentration. However, because GABA itself has difficulty crossing the blood-brain barrier (BBB), the effectiveness of exogenous GABA supplementation is limited. Therefore, improving the bioavailability of GABA and prolonging its duration of action has become an important issue in drug development. In recent years, with the advancement of drug delivery technology, the development of GABA sustained-release formulations has become a hot topic. Sustained-release formulations, through specific carriers or technologies, can control the release rate of GABA, maintaining a stable blood concentration in the body, thereby prolonging the duration of action and improving efficacy. Compared with conventional formulations, GABA sustained-release formulations have the following advantages: First, sustained-release formulations can reduce the frequency of administration, improving patient compliance; second, by avoiding drastic fluctuations in drug concentration, sustained-release formulations can reduce the incidence of adverse reactions; finally, sustained-release technology can optimize the pharmacokinetic properties of GABA, allowing it to act more effectively on the target, thereby improving therapeutic effects.

[0003] Powder coating technology is a process that coats drug particles with one or more layers of functional materials to improve the physicochemical properties of drugs, optimize their release characteristics, and enhance the patient's medication experience. This technology is an important branch of pharmaceutical formulation and is widely used in the development and production of solid dosage forms. Compared to traditional tablet or granule coating technologies, powder coating technology offers greater flexibility and applicability, especially suitable for micronized drugs, poorly soluble drugs, and drugs sensitive to humidity and temperature. Originating in the mid-20th century, powder coating technology arose as the pharmaceutical industry's demands for drug performance increased, and traditional tablet coating technologies could no longer meet the needs of certain specialized drugs. Powder coating technology was developed to address this, its core being the formation of a uniform and stable coating layer on the surface of drug powder through specific processing methods. This technology not only improves the flowability, stability, and compressibility of drugs but also enables sustained-release, controlled-release, or targeted release, thereby improving drug efficacy and safety. The implementation of powder coating technology relies on advanced coating equipment and processes. Commonly used coating methods include fluidized bed coating, spray drying coating, and mechanical coating. Fluidized bed coating is the most common method, where drug powder is suspended in an airflow and a coating solution is sprayed onto it, forming a uniform film on the particle surface. This technology offers advantages such as high efficiency, strong controllability, and wide applicability. Spray drying coating, on the other hand, involves simultaneously atomizing and drying the drug and coating material to form a coated powder, suitable for heat-sensitive drugs. The selection of the coating material is crucial in powder coating technology. Commonly used coating materials include cellulose-based materials (such as hydroxypropyl methylcellulose and ethyl cellulose), acrylic resins (such as the Eudragit series), polyvinyl alcohol (PVA), and natural polymers (such as chitosan). These materials not only possess good film-forming properties and biocompatibility but can also be functionalized according to the characteristics of the drug. For example, by selecting pH-sensitive materials, drug release at specific sites can be achieved; by using sustained-release materials, the duration of drug action can be prolonged. The application of powder coating technology provides more possibilities for drug formulation design. For example, in the development of poorly soluble drugs, powder coating technology can improve drug solubility and bioavailability; in the field of pediatric medications, masking the bitterness or irritating odor of drugs through coating can improve patient compliance; in multi-unit microparticle systems, powder coating technology can achieve precise drug release and targeted delivery. Furthermore, powder coating technology can also be used to improve drug stability, preventing degradation due to moisture, oxidation, or photodegradation.

[0004] Sodium alginate is a natural polysaccharide, primarily extracted from seaweed, possessing excellent biocompatibility and biodegradability, and is widely used in pharmaceutical formulations. As a coating material, sodium alginate has many significant characteristics and advantages: First, upon contact with water in the gastrointestinal tract, sodium alginate forms a stable gel layer, which effectively delays drug release, thus achieving a sustained-release effect. This sustained-release effect not only reduces drug toxicity but also improves therapeutic efficacy. Second, sodium alginate coating protects drugs from the acidic environment of the stomach, improving drug stability, especially suitable for acid-sensitive drugs. Third, sodium alginate coating can mask unpleasant drug tastes, improving patient compliance. Finally, sodium alginate is a naturally derived material with good biocompatibility, biodegradability, no toxic side effects on humans, and high safety, making it suitable for oral formulations. However, sodium alginate as a coating material also has several drawbacks, such as low mechanical strength, poor long-term stability, unsatisfactory sustained-release performance, and significant burst release when encapsulating small-molecule water-soluble drugs, resulting in rapid drug release. Therefore, the above deficiencies need to be compensated for through reasonable coating formulation design. Summary of the Invention

[0005] In view of the shortcomings of the prior art described above, the purpose of this invention is to provide a GABA sustained-release coated powder, its preparation method and application.

[0006] To achieve the above and other related objectives, the first aspect of this application provides a GABA sustained-release coated powder, the GABA sustained-release powder comprising GABA powder and a coating layer, the coating layer comprising sodium alginate, a polymer matrix, a small molecule filler and an emulsifier in a weight ratio of 0.2~2.5:1~10:1~20:0.5~8.

[0007] The second aspect of this application provides a method for preparing the above-mentioned GABA sustained-release coated powder, comprising the following steps: 1) homogenizing sodium alginate, polymer substrate, small molecule filler and emulsifier to obtain a coating solution; 2) adding the above-mentioned coating solution to GABA powder and drying to obtain GABA sustained-release coated powder.

[0008] In summary, this invention provides a GABA sustained-release coated powder, its preparation method, and its application, and achieves the following beneficial effects:

[0009] 1) By combining sodium alginate with specific functional ingredients, sodium alginate forms an interpenetrating polymer network through its own hydrogen bonding, and hydroxypropyl methylcellulose acts as a second network interpenetrating within it, forming a synchronous interpenetrating network, which increases the mechanical strength of the sodium alginate coating layer and improves the stability of the product.

[0010] 2) By combining sodium alginate with specific functional ingredients, small molecule fillers and glyceryl monostearate fill the pores in the sodium alginate and hydroxypropyl methylcellulose network, improving density and regulating the microenvironment to slow down the diffusion rate of GABA, thereby achieving a sustained-release effect. This results in the sustained-release effect of small molecule water-soluble drug GABA powder and improves product efficacy.

[0011] 3) By combining a variety of functional materials, the stability of the sodium alginate coating layer is improved. By using food excipients, sustained release of small molecule water-soluble drugs is achieved. When applied to the coating of small molecule drugs such as GABA, it helps to improve their bioavailability and efficacy. Attached Figure Description

[0012] Figure 1 The graph shows the dissolution test results of the GABA sustained-release coating powder in this application. Detailed Implementation

[0013] The technical solution of the present invention will be clearly and completely described below. Obviously, the described embodiments are only some, not all, of the embodiments of the present invention. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0014] Before further describing specific embodiments of the present invention, it should be understood that the scope of protection of the present invention is not limited to the specific embodiments described below; it should also be understood that the terminology used in the embodiments of the present invention is for describing specific embodiments and not for limiting the scope of protection of the present invention; in the specification and claims of the present invention, unless otherwise expressly stated in the text, the singular forms "a", "an" and "this" include the plural forms.

[0015] When numerical ranges are given in the embodiments, it should be understood that, unless otherwise stated in the present invention, both endpoints of each numerical range and any value between the two endpoints may be selected. Unless otherwise defined, all technical and scientific terms used in this invention have the same meaning as commonly understood by one of ordinary skill in the art. In addition to the specific methods, apparatus, and materials used in the embodiments, based on the knowledge of the prior art possessed by one of ordinary skill in the art and the description of this invention, any prior art methods, apparatus, and materials similar to or equivalent to those described, apparatus, and materials in the embodiments of this invention may be used to implement the present invention.

[0016] This application first provides a GABA sustained-release coated powder, which includes GABA powder and a coating layer. The coating layer includes sodium alginate, a polymer matrix, a small molecule filler, and an emulsifier in a weight ratio of 0.2~2.5:1~10:1~20:0.5~8.

[0017] In some embodiments, the polymeric substrate is selected from one or more of hydroxypropyl methylcellulose, polyethylene glycol, polyvinyl alcohol, and sodium carboxymethyl cellulose; the small molecule filler is selected from one or more of inulin, mannose, lactose, glucose, trehalose, galactooligosaccharides, fructooligosaccharides, stachyose, and resistant dextrin; and the emulsifier is selected from one or more of glyceryl monostearate, lecithin, polyglycerol fatty acid esters, caprylic / capric glycerides, phytosterols, and phytosterol esters.

[0018] In some embodiments, the coating layer may include sodium alginate, a polymeric matrix, a small molecule filler, and an emulsifier in a weight ratio of 0.5~2.5:1.5~8:2~15:1~6. In some embodiments, the coating layer may include sodium alginate, a polymeric matrix, a small molecule filler, and an emulsifier in a weight ratio of 0.5~2:2~5:4~8:1~3. In some embodiments, the coating layer may include sodium alginate, a polymeric matrix, a small molecule filler, and an emulsifier in a weight ratio of 0.5~1:2~2.5:4~6:1~1.5.

[0019] In some embodiments, the weight ratio of the GABA powder to the coating layer can be 85~95:5~15.

[0020] Preferably, the weight ratio of GABA powder to the coating layer can be 88~94:6~12. More preferably, the weight ratio of GABA powder to the coating layer can be 89~92.5:7.5~11.

[0021] This application also provides a method for preparing the above-mentioned GABA sustained-release coated powder, comprising the following steps: 1) homogenizing sodium alginate, polymer substrate, small molecule filler and emulsifier to obtain a coating solution; 2) adding the above-mentioned coating solution to GABA powder and drying to obtain GABA sustained-release coated powder.

[0022] In some embodiments of the present invention, step 1) further includes: swelling sodium alginate and polymer substrate separately and then mixing them, adding small molecule filler and dissolving it completely, then adding emulsifier and homogenizing to obtain coating solution.

[0023] In some embodiments, the polymeric substrate is selected from one or more of hydroxypropyl methylcellulose, polyethylene glycol, polyvinyl alcohol, and sodium carboxymethyl cellulose; the small molecule filler is selected from one or more of inulin, mannose, lactose, glucose, trehalose, galactooligosaccharides, fructooligosaccharides, stachyose, and resistant dextrin; and the emulsifier is selected from one or more of glyceryl monostearate, lecithin, polyglycerol fatty acid esters, caprylic / capric glycerides, phytosterols, and phytosterol esters.

[0024] In some embodiments, during the preparation of the coating solution, the weight ratio of sodium alginate, polymeric substrate, small molecule filler, and emulsifier is 0.2~2.5:1~10:1~20:0.5~8. In some embodiments, the weight ratio of sodium alginate, polymeric substrate, small molecule filler, and emulsifier is 0.5~2.5:1.5~8:2~15:1~6. In some embodiments, the weight ratio of sodium alginate, polymeric substrate, small molecule filler, and emulsifier is 0.5~2:2~5:4~8:1~3. In some embodiments, the weight ratio of sodium alginate, polymeric substrate, small molecule filler, and emulsifier is 0.5~1:2~2.5:4~6:1~1.5.

[0025] In some embodiments of the present invention, in step 2), the particle size of the GABA powder is selected from 5 to 300 μm, preferably 20 to 200 μm.

[0026] In some embodiments, during the preparation of the GABA sustained-release coated powder, the weight ratio of GABA powder to coating solution can be 85-95:5-15. In some embodiments, the weight ratio of GABA powder to coating solution can be 88-94:6-12. In some embodiments, the weight ratio of GABA powder to coating solution can be 89-92.5:7.5-11.

[0027] In some embodiments, GABA powder and coating solution can be used for powder coating in a fluidized bed. In some embodiments, the coating solution can be added via bottom spray or side spray technology. A fluidized bed utilizes a rapidly rising airflow from the bottom to suspend and fluidize the pellets within the coating chamber. The direction of the spray is aligned with the direction of the moving pellets. The coating solution or suspension is atomized by spray guns on the side walls or bottom, causing the coating solution to form droplets of a specific size that adhere to the powder surface. Through heat exchange within the fluidized bed, coating and drying are repeated until the desired thickness is achieved. This method is simple to operate, has a fast drying speed, and produces a high-quality coating film, which is beneficial for improving the quality of the formulated product.

[0028] In some embodiments, during the preparation of the GABA sustained-release coated powder, the pressure of the fluidized bed is 0.05~0.2 MPa, and the flow rate of the coating solution is 20~200 mL / min.

[0029] In some embodiments, in step 2), the GABA powder and coating solution can be controlled at 33–45°C.

[0030] In some embodiments, the drying is carried out in a fluidized bed for 20-30 minutes.

[0031] The present invention also provides the use of the above-mentioned GABA sustained-release coating powder in the preparation of pharmaceuticals, functional foods, and health foods.

[0032] The following specific examples illustrate the implementation of the present invention. Those skilled in the art can easily understand other advantages and effects of the present invention from the content disclosed in this specification. The present invention can also be implemented or applied through other different specific embodiments, and various details in this specification can also be modified or changed based on different viewpoints and applications without departing from the spirit of the present invention.

[0033] Unless otherwise specified, the experimental methods used in the following examples are conventional methods. Unless otherwise specified, the experimental materials used in the following examples were all purchased from conventional biochemical reagent companies. Quantitative experiments in the following examples were all performed in triplicate, and the results were averaged.

[0034] Determination of GABA sustained-release coating powder release rate: The method was performed according to the "Second Method (Paddle Method)" of the Chinese Pharmacopoeia's Dissolution and Release Determination. 1 g of sample was accurately weighed and placed in a dry 14000 kD dialysis bag, which was then fixed to the end of the stir bar in the dissolution apparatus. The dissolution medium was 1000 mL of phosphate buffer (pH 7.6) at 37℃ ± 0.5℃, and the stir bar speed was 100 rpm. Sampling times were 1, 2, 4, and 8 h. The release rate was determined using the 2,4-dinitrofluorophenyl amino acid derivatization method.

[0035] Example 1

[0036] GABA powder: particle size 50 μm, addition amount 500g.

[0037] The coating solution consisted of 0.5% sodium alginate, 2% hydroxypropyl methylcellulose, 4% lactose, and 1% glyceryl monostearate. Coating was performed using a fluidized bed bottom spray process with an atomization pressure of 0.1 MPa, a material temperature of 40℃, and a spray flow rate of 30 mL / min. This yielded a sustained-release GABA-coated powder.

[0038] The release rate of GABA sustained-release coated powder was investigated.

[0039] The results are as follows Figure 1 As shown, the GABA sustained-release coated powder has good sustained-release properties, with a release time extended to 6 hours. Observation of the coating showed that the coating layer did not fall off.

[0040] Example 2

[0041] GABA powder: particle size 100 μm, addition amount 500 g. Coating solution composition: sodium alginate 0.75%, hydroxypropyl methylcellulose 2%, trehalose 6%, lecithin 1.5%. Coating was performed using a fluidized bed bottom spray process, atomization pressure 0.1 MPa, material temperature 40℃, spray flow rate 30 mL / min. A sustained-release coated GABA powder was prepared.

[0042] The release rate of GABA-coated powder was investigated. The results are as follows: Figure 1 As shown, the GABA sustained-release coated powder has good sustained-release properties, with a release time extended to 8 hours. Observation of the coating showed that the coating layer did not fall off.

[0043] Example 3

[0044] GABA powder: particle size 150 μm, addition amount 500 g. Coating solution composition: sodium alginate 1%, polyethylene glycol 2.5%, galactooligosaccharides 6%, caprylic / capric triglycerides 1.5%. Coating was performed using a fluidized bed bottom spray process, atomization pressure 0.1 MPa, material temperature 40℃, spray flow rate 30 mL / min. A sustained-release coated GABA powder was prepared.

[0045] Release rate test results are as follows Figure 1 As shown, the GABA sustained-release coated powder has good sustained-release properties, with the release time extended to 8 hours. Observation of the coating showed that the coating layer did not fall off.

[0046] Comparative Example 1

[0047] GABA powder: particle size 100 μm, addition amount 500g. Coating solution composition: sodium alginate 1%, hydroxypropyl methylcellulose 2%, lactose 6%. Coating was performed using a fluidized bed bottom spray process, atomization pressure 0.1 MPa, material temperature 40℃, spray flow rate 30 mL / min. A sustained-release coated GABA powder was prepared.

[0048] Release rate test results are as follows Figure 1 As shown, the GABA sustained-release coated powder does not have sustained-release properties, with a release time of 3 hours, and observation of the coating revealed that the coating layer does not fall off.

[0049] Comparative Example 2

[0050] GABA powder: particle size 100 μm. Coating solution composition: sodium alginate 1%. Coating was performed using a fluidized bed bottom spray process, with an atomization pressure of 0.1 MPa, a material temperature of 40℃, and a spray flow rate of 30 mL / min. A sustained-release coated GABA powder was prepared.

[0051] Release rate test results are as follows Figure 1As shown, the GABA sustained-release coated powder does not have sustained-release properties, with a release time of 2 hours, and observation of the coating revealed that the coating layer is prone to peeling off.

[0052] In summary, the above description is merely a preferred embodiment of the present invention and does not constitute any limitation on the present invention in any form or substance. It should be noted that those skilled in the art can make various improvements and additions without departing from the method of the present invention, and these improvements and additions should also be considered within the scope of protection of the present invention. Any modifications, alterations, and equivalent changes made by those skilled in the art based on the above-disclosed technical content without departing from the spirit and scope of the present invention are equivalent embodiments of the present invention. Furthermore, any modifications, alterations, and evolutions made to the above embodiments based on the essential technology of the present invention still fall within the scope of the technical solution of the present invention.

Claims

1. A GABA sustained-release coated powder, wherein the GABA sustained-release powder comprises GABA powder and a coating layer, wherein the coating layer comprises sodium alginate, a polymer matrix, a small molecule filler and an emulsifier in a weight ratio of 0.2~2.5:1~10:1~20:0.5~8.

2. The GABA sustained-release coated powder as described in claim 1, characterized in that, The polymeric substrate is selected from one or more of hydroxypropyl methylcellulose, polyethylene glycol, polyvinyl alcohol, and sodium carboxymethyl cellulose; and / or the small molecule filler is selected from one or more of inulin, mannose, lactose, glucose, trehalose, galactooligosaccharides, fructooligosaccharides, stachyose, and resistant dextrin; and / or the emulsifier is selected from one or more of glyceryl monostearate, lecithin, polyglycerol fatty acid esters, caprylic / capric glycerides, phytosterols, and phytosterol esters.

3. The GABA sustained-release coated powder as described in claim 1, characterized in that, The coating layer comprises sodium alginate, a polymer matrix, small molecule fillers, and an emulsifier in a weight ratio of 0.5~2.5:1.5~8:2~15:1~6.

4. The GABA sustained-release coated powder as described in claim 1, characterized in that, The weight ratio of GABA powder to the coating layer can be 85~95:5~15.

5. The method for preparing GABA sustained-release coated powder as described in claim 1, comprising the following steps: 1) homogenizing sodium alginate, polymer substrate, small molecule filler and emulsifier to obtain a coating solution; 2) adding the above coating solution to GABA powder and drying to obtain GABA sustained-release coated powder.

6. The preparation method according to claim 5, characterized in that, The polymeric substrate is selected from one or more of hydroxypropyl methylcellulose, polyethylene glycol, polyvinyl alcohol, and sodium carboxymethyl cellulose; and / or the small molecule filler is selected from one or more of inulin, mannose, lactose, glucose, trehalose, galactooligosaccharides, fructooligosaccharides, stachyose, and resistant dextrin; and / or the emulsifier is selected from one or more of glyceryl monostearate, lecithin, polyglycerol fatty acid esters, caprylic / capric glycerides, phytosterols, and phytosterol esters.

7. The preparation method according to claim 5, characterized in that, The weight ratio of sodium alginate, polymer substrate, small molecule filler and emulsifier is 0.2~2.5:1~10:1~20:0.5~8; and / or, the weight ratio of GABA powder to coating solution is 85~95:5~15; and / or, the particle size of GABA powder is selected from 5~300 μm, preferably 20~200 μm.

8. The preparation method according to claim 5, characterized in that, The GABA powder and coating solution are placed in a fluidized bed for powder coating; and / or, the pressure of the fluidized bed is 0.05~0.2 MPa, and the flow rate of the coating solution is 20~200 mL / min.

9. The preparation method according to claim 5, characterized in that, In step 2), the GABA powder and coating solution are controlled at 33-45°C; and / or the drying is carried out in a fluidized bed for 20-30 minutes.

10. The use of the GABA sustained-release coating powder as described in any one of claims 1 to 4 in the preparation of pharmaceuticals, functional foods, and health foods.

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