A sustained-release tablet with an abuse-prevention function

Abstract

The utility model discloses a kind of sustained-release tablets with anti-abuse function, comprising: first shielding layer, drug-containing layer and second shielding layer;The drug-containing layer has opposite top surface and bottom surface, and the side peripheral surface of connecting the top surface and bottom surface;The first shielding layer and the second shielding layer respectively cover the top surface and bottom surface of the drug-containing layer, jointly form the three-layer tablet core that the drug-containing layer is clamped in middle, and make the side peripheral surface of the drug-containing layer expose;Wherein, the drug-containing layer includes easily abused drug and pharmaceutically acceptable adjuvant, the first shielding layer and the second shielding layer are all high molecular material layer;And at least one sustained-release coating layer and gastric soluble coating layer that surface of the three-layer tablet core is successively coated;The easily abused drug includes hydrocodone bitartrate, oxycodone hydrochloride or hydromorphone hydrochloride.

Description

Technical Field

[0001] This utility model relates to the field of pharmaceutical formulation technology, and more specifically, to a sustained-release tablet with anti-abuse function. Background Technology

[0002] In the pharmaceutical field, sustained-release tablets are widely used in various drug formulations due to their ability to achieve long-term drug release, reduce the frequency of dosing, and maintain stable blood drug concentrations. This is especially true for patients requiring long-term medication, with 24-hour sustained-release formulations further improving medication convenience and treatment adherence. However, for drugs prone to abuse, such as opioids and psychotropic substances, existing sustained-release tablets generally lack effective abuse prevention designs. Abusers often obtain the active ingredients through physical crushing, solvent extraction, nasal inhalation, or injection, which not only destroys the sustained-release structure, leading to a sudden and massive release of the drug and causing serious safety hazards such as overdose and poisoning, but also adversely affects public health and safety.

[0003] Therefore, developing a sustained-release tablet that can stably achieve long-lasting sustained-release function, effectively prevent various abuse risks through structural innovation, and does not affect drug release characteristics has become an urgent technical problem to be solved in the current pharmaceutical field. Utility Model Content

[0004] This utility model embodiment provides a sustained-release tablet with anti-abuse function, comprising: A first shielding layer, a drug-containing layer, and a second shielding layer; the drug-containing layer has opposing top and bottom surfaces, and a side peripheral surface connecting the top and bottom surfaces; the first and second shielding layers respectively cover the top and bottom surfaces of the drug-containing layer, together forming a three-layer core that sandwiches the drug-containing layer in the middle and exposes the side peripheral surface of the drug-containing layer; wherein the drug-containing layer contains an abused drug and pharmaceutically acceptable excipients, and both the first and second shielding layers are polymer material layers; and At least one sustained-release coating layer and a gastrosoluble coating layer are sequentially coated on the surface of the three-layer tablet core.

[0005] In one exemplary embodiment, the thickness ratio of the first shielding layer, the drug-containing layer, and the second shielding layer in the three-layer tablet core is (0.8 to 1.5): 1: (0.8 to 1.5), for example, but not limited to, 0.8: 1: 0.8, 1: 1: 1, or 1.4: 1: 1.4. This thickness ratio range ensures that the sustained-release tablet has good mechanical strength, effectively resisting external force crushing, while also taking into account the patient's ease of swallowing.

[0006] In one exemplary embodiment, the diameter of the sustained-release tablet is 9 mm to 17 mm, such as, but not limited to, 9 mm, 9.5 mm, 10 mm, 10.5 mm, 11 mm, 11.5 mm, 12 mm, 12.5 mm, 13 mm, 13.5 mm, 14 mm, 14.5 mm, 15 mm, 15.5 mm, 16 mm, 16.5 mm or 17 mm, optionally 11 mm to 12.5 mm.

[0007] In one exemplary embodiment, the diameter of the three-layer core is 8 mm to 16 mm, such as, but not limited to, 8 mm, 8.5 mm, 9 mm, 9.5 mm, 10 mm, 10.5 mm, 11 mm, 11.5 mm, 12 mm, 12.5 mm, 13 mm, 13.5 mm, 14 mm, 14.5 mm, 15 mm, 15.5 mm or 16 mm, and optionally 10 mm to 12 mm.

[0008] In one exemplary embodiment, in the three-layer wafer core, the thickness of both the first shielding layer and the second shielding layer is ≥2 mm, and the thickness of the drug-containing layer is 2.5 mm to 3.5 mm. In another exemplary embodiment, the thicknesses of the first shielding layer, the drug-containing layer, and the second shielding layer are 2.4 mm, 3.0 mm, and 2.4 mm, respectively. In yet another exemplary embodiment, the thicknesses of the first shielding layer, the drug-containing layer, and the second shielding layer are 3.0 mm, 3.0 mm, and 3.0 mm, respectively. In yet another exemplary embodiment, the thicknesses of the first shielding layer, the drug-containing layer, and the second shielding layer are 3.5 mm, 2.5 mm, and 3.5 mm, respectively.

[0009] In one exemplary embodiment, the polymer material layer may be composed of a thermoplastic polymer material that has water-swellable properties.

[0010] In one exemplary embodiment, the polymer material layer may also be composed of a thermoplastic polymer material with water-swellable properties and other polymer materials.

[0011] A water-swellable thermoplastic polymer can soften or melt during heat treatment, flowing to fill the pores between particles, and upon cooling to form a tough, non-powdering, and high-viscosity gel-like continuous matrix. In one exemplary embodiment, the water-swellable thermoplastic polymer can soften or melt at a temperature of 40°C to 100°C, optionally 70°C to 80°C. In another exemplary embodiment, the water-swellable thermoplastic polymer is selected from any one or more of polyethylene oxide, ethylene oxide-propylene oxide copolymers, and mixtures thereof. In yet another exemplary embodiment, the water-swellable thermoplastic polymer is polyethylene oxide.

[0012] In one exemplary embodiment, the other polymeric material may be selected from any one or more of hydroxypropyl methylcellulose, sodium alginate, methylcellulose, ethylcellulose, etc.

[0013] In one exemplary embodiment, the water-swellable thermoplastic polymer material in the polymer material layer is a continuous matrix phase that melts and then solidifies.

[0014] In one exemplary embodiment, a lubricant is dispersed in the polymer material layer. The addition of the lubricant can improve the flowability and release properties of the polymer material during tableting. The amount of lubricant added can be selected as needed, for example, it can account for 0.1% to 1.5% of the total mass of the polymer material layer.

[0015] In one exemplary embodiment, the sustained-release tablet has a first sustained-release coating layer, a second sustained-release coating layer, and a gastrointestinal coating layer sequentially coating the surface of the three-layer tablet core.

[0016] In one exemplary embodiment, the thickness ratio of the first sustained-release coating layer to the second sustained-release coating layer is 1:(50 to 350), such as, but not limited to, 1:50, 1:80, 1:100, 1:120, 1:150, 1:180, 1:200, 1:220, 1:250, 1:280, 1:300, 1:320, or 1:350. This thickness ratio can form a gradient sustained-release structure, achieving both a long-lasting and stable sustained-release effect and effectively extending the time window required for solvent extraction by abusers.

[0017] In one exemplary embodiment, the thickness of the first sustained-release coating layer is 3 μm to 12 μm, and the thickness of the second sustained-release coating layer is 0.7 mm to 1.0 mm. In another exemplary embodiment, the thickness of the first sustained-release coating layer is 8 μm, and the thickness of the second sustained-release tablet is 0.85 mm. In yet another exemplary embodiment, the thickness of the first sustained-release coating layer is 6 μm, and the thickness of the second sustained-release tablet is 0.9 mm. In yet another exemplary embodiment, the thickness of the first sustained-release coating layer is 10 μm, and the thickness of the second sustained-release tablet is 0.8 mm.

[0018] In one exemplary embodiment, the cross-sectional shape of the sustained-release tablet parallel to the top surface of the drug-containing layer can be circular, elliptical, triangular, rhomboid, hexagonal, or butterfly-shaped, etc.

[0019] In this invention, the sustained-release tablet with anti-abuse function is applicable to any drug that needs to be formulated into an anti-abuse sustained-release dosage form. In an exemplary embodiment, the drug-containing layer may contain one or more of the following: opioids or psychotropic drugs, including but not limited to hydrocodone bitartrate, oxycodone hydrochloride, hydromorphone hydrochloride, tapentadone hydrochloride, or combinations of the above drugs with acetaminophen, and combinations of dextromethorphan and bupropion. Pharmaceutically acceptable excipients and their amounts may be conventionally selected according to the formulation requirements, and may be selected from one or more of the following: stabilizers, fillers, disintegrants, binders, polymers, and lubricants.

[0020] In one exemplary embodiment, the drug-containing layer comprises hydrocodone bitartrate, a stabilizer, a filler, a disintegrant, a binder, a polymeric material, and a lubricant. Hydrocodone bitartrate accounts for 6% to 40% of the total weight of the drug-containing layer; the stabilizer is butylated hydroxytoluene (BHT), accounting for 0.1% to 0.2% of the total weight of the drug-containing layer; the filler is microcrystalline cellulose, accounting for 3% to 10% of the total weight of the drug-containing layer; the disintegrant is croscarmellose sodium, accounting for 0.2% to 2% of the total weight of the drug-containing layer; the binder is copovidone, accounting for 0.2% to 2% of the total weight of the drug-containing layer; the polymeric material is polyethylene oxide, accounting for 45% to 90% of the total weight of the drug-containing layer; and the lubricant is magnesium stearate, accounting for 0.1% to 1.5% of the total weight of the drug-containing layer. It should be clarified that the specific components and their amounts listed above are only one of the optional embodiments of this utility model and are not a limitation on the composition of the drug-containing layer material, nor do they constitute any limitation on the shape and structure of the product protected by this utility model.

[0021] In this embodiment of the invention, the coating materials used in each sustained-release coating layer and the gastric-soluble coating layer are all known conventional materials in the art that achieve sustained-release or gastric-soluble functions. The composition of the first sustained-release coating layer and the second sustained-release coating layer may be the same or different, and the main components may include any one or more of the sustained-release coating material, film-forming material, etc. The sustained-release coating material may be selected from any one or more of ethyl cellulose, methacrylate copolymer, aminomethacrylate copolymer, cellulose acetate, hydroxypropyl methylcellulose, polyoxyethylene, polyvinyl alcohol, acrylic resin, etc.; the film-forming material may be selected from any one or more of hydroxypropyl methylcellulose, hydroxypropyl cellulose, polyvinylpyrrolidone, polyvinyl alcohol, acrylic resin, etc. The above-mentioned coating materials may also have a certain amount of plasticizer added as needed. In an exemplary embodiment, the composition of the first sustained-release coating layer and the second sustained-release coating layer includes ethyl cellulose and Opadry gastric-soluble coating powder (from Colorcon, model YS-1-7006), and the ratio of the two can be adjusted according to the desired drug release procedure requirements. The main components of the gastrointestinal coating layer can be selected from any one or more of hydroxypropyl cellulose, hydroxypropyl methylcellulose, polyvinylpyrrolidone, and polyvinylacetal diethylaminoacetic acid. In an exemplary embodiment, the gastrointestinal coating layer can be Opadry gastrointestinal coating powder (from Colorcon, model 85F110185). It should be noted that the specific components and their amounts listed above are only one of the optional embodiments of this utility model, and are not a limitation on the composition of the sustained-release coating layer and the gastrointestinal coating layer, nor do they constitute any limitation on the shape and structure of the product protected by this utility model.

[0022] The three-layer tablet core of the sustained-release tablet with anti-abuse function provided in this embodiment of the invention can be prepared by tableting using conventional equipment. For example, the three-layer tablet core can be prepared by the following method: first filling the first shielding layer material, pre-compressing, then filling the drug-containing layer material, pre-compressing, and finally filling the second shielding layer and compressing to form the three-layer tablet core. When the three-layer tablet core needs to be thermosetting, the compressed three-layer tablet core or the three-layer tablet core coated with a sustained-release coating layer can be heat-treated at a temperature equal to or higher than the softening point of the polymer material and then cooled. For example, when forming a melt-re-cured polyoxyethylene continuous matrix phase, the three-layer tablet core coated with a sustained-release coating layer can be heat-treated at a temperature of 70°C to 80°C and then cooled. In the sustained-release tablet with anti-abuse function provided in this embodiment of the invention, the sustained-release coating layer and the gastrointestinal coating layer can be prepared using conventional coating equipment and conventional coating methods and conditions.

[0023] The beneficial effects of this utility model's technical solution include: 1. The anti-abuse function of the sustained-release tablets provided in this embodiment is mainly undertaken by the three-layer tablet core. The gastric-soluble coating layer can isolate, color, and control the initial release of the drug in the stomach. The long-acting sustained-release function is jointly undertaken by the three-layer tablet core and the sustained-release coating layer, ensuring that the tablet takes effect smoothly after administration. After oral administration, the gastric-soluble coating layer dissolves rapidly in gastric juice, exposing the sustained-release coating layer, controlling the slow release of the drug. When multiple (e.g., two) sustained-release coating layers are present, the multiple sustained-release coating layers can form a multi-level (e.g., two-level) release barrier, controlling the slow release of the drug according to a predetermined program (e.g., 24-hour long-acting release). The functional zoning design ensures that the drug is released smoothly at a predetermined rate during normal administration, guaranteeing the therapeutic effect.

[0024] 2. The sustained-release tablet with anti-abuse function provided in this embodiment of the invention utilizes a three-layer core structure consisting of a first shielding layer, a drug-containing layer, and a second shielding layer. The shielding layer forms a high-viscosity gel layer upon contact with a solvent, effectively hindering solvent penetration and drug extraction, thus achieving the effect of preventing injection abuse. The shielding layer, made of a polymer material, gives the tablet high mechanical strength, effectively resisting external force crushing, making it difficult for abusers to pulverize the tablet into a fine powder suitable for nasal inhalation. Simultaneously, when abusers attempt to extract the drug through forceful physical crushing, the protection of the shielding layer, and the fact that fine-sized particles from the shielding layer are mixed with the drug-containing layer particles and difficult to separate, reduces the recovery of drug from the fine-sized particles (particles below 500 μm) suitable for nasal inhalation. Therefore, the structural shielding effect achieves the purpose of preventing abuse.

[0025] 3. In the sustained-release tablet with anti-abuse function provided in this embodiment of the invention, the first and second shielding layers can be composed of a thermoplastic polymer material (such as polyoxyethylene) with water-swellable properties. The thermoplastic polymer material in the polymer layer can be thermosetting to form a continuous matrix phase of melt-re-solidification. This structure, while maintaining the tablet's hardness, further increases the tablet's elastic deformation capability. When an abuser attempts to break the tablet using physical methods such as hammering or crushing, the shielding layers on both sides will elastically deform under pressure to absorb the impact energy, making it difficult to shatter into powder, thus effectively preventing the drug-containing layer from being separated and extracted. Simultaneously, the shielding layer can still form a high-viscosity gel barrier after contact with water, providing double protection against abuse.

[0026] 4. Test examples show that the sustained-release tablets with anti-abuse function provided by the present invention have better anti-physical abuse and anti-solvent extraction abuse effects than chip-encapsulated tablets.

[0027] Other features and advantages of this invention will be set forth in the description which follows, and will be apparent in part from the description, or may be learned by practicing the invention. The objects and other advantages of this invention can be realized and obtained by means of the structures particularly pointed out in the description and the drawings. Attached Figure Description

[0028] The accompanying drawings are provided to further illustrate the technical solution of this utility model and constitute a part of the specification. They are used together with the embodiments of this application to explain the technical solution of this utility model and do not constitute a limitation on the technical solution of this utility model.

[0029] Figure 1 This is a cross-sectional structural diagram of the sustained-release tablet according to an embodiment of the present invention; wherein, 1-first shielding layer, 2-drug-containing layer, 3-second shielding layer, 4-first sustained-release coating layer, 5-second sustained-release coating layer, and 6-gastric-soluble coating layer A.

[0030] Figure 2 This is a schematic diagram of the cross-sectional structure of the chip in the comparative example; where 7 is the core layer, 8 is the outer shell layer, and 9 is the gastric coating layer B.

[0031] Figure 3 The dissolution curve is shown in Example 1.

[0032] Figure 4 The dissolution curve is shown in Example 2.

[0033] Figure 5 The dissolution curve is shown in Example 3.

[0034] Figure 6 The dissolution curves are for comparison. Detailed Implementation

[0035] To make the objectives, technical solutions, and advantages of this utility model clearer, the embodiments of this utility model will be described in detail below with reference to the accompanying drawings. It should be noted that, unless otherwise specified, the embodiments and features described in this application can be arbitrarily combined with each other.

[0036] All raw and auxiliary materials used in the following examples are commercially available.

[0037] Example 1 Reference Figure 1 As shown, this embodiment provides a sustained-release tablet with anti-abuse function, comprising: A first shielding layer 1, a drug-containing layer 2, and a second shielding layer 3; the drug-containing layer 2 has a top surface and a bottom surface opposite to each other, and a side peripheral surface connecting the top surface and the bottom surface; the first shielding layer 1 and the second shielding layer 3 respectively cover the top surface and the bottom surface of the drug-containing layer 2, together forming a three-layer core that sandwiches the drug-containing layer 2 in the middle and exposes the side peripheral surface of the drug-containing layer; and The first sustained-release coating layer 4, the second sustained-release coating layer 5, and the gastrointestinal coating layer A 6 are sequentially coated on the surface of the three-layer tablet core.

[0038] The sustained-release tablets have a diameter of 12 mm, and the three-layer tablet core has a diameter of 11 mm. The thicknesses of the first shielding layer 1, the drug-containing layer 2, and the second shielding layer 3 are 2.4 mm, 3.0 mm, and 2.4 mm, respectively, with a thickness ratio of 0.8:1:0.8. The thickness of the first sustained-release coating layer 4 is 8 μm, and the thickness of the second sustained-release coating layer 5 is 0.85 mm.

[0039] The formulation composition of sustained-release tablets is shown in Table 1 below.

[0040] Table 1 Methods for preparing sustained-release tablets include: (1) Preparation of drug-containing layer: After sieving, hydrocodone bitartrate, 75% of copovidone in the prescription amount, butylated hydroxytoluene (BHT) and microcrystalline cellulose are mixed, the remaining copovidone solution is added, wet granulation is performed, drying is carried out, and after granulation, polyoxyethylene, crosslinked sodium carboxymethyl cellulose and magnesium stearate are added and mixed evenly. (2) Configure the first shielding layer: Mix polyoxyethylene and magnesium stearate evenly; (3) Configure the second shielding layer: Mix polyoxyethylene and magnesium stearate evenly; (4) Preparation of three-layer tablet core: fill the first shielding layer material, pre-press, then fill the drug-containing layer material, pre-press, and finally fill the second shielding layer and press to form a three-layer tablet core; (5) First sustained-release coating layer coating: The first sustained-release coating layer coating is carried out in a coating pan; (6) Heat curing: After the first slow-release layer coating is completed, heat curing is carried out once in a coating pan or oven, that is, heat treatment is carried out at a temperature equal to or higher than the melting point of polyoxyethylene and then cooling treatment is carried out, so that the polyoxyethylene in the core of the three-layer sheet melts and then solidifies, and the polyoxyethylene in the first shielding layer and the second shielding layer is a continuous matrix phase of melt and solidification; wherein, the heat curing conditions are: 70 ℃ to 80 ℃, 20 min; (7) Second sustained-release coating: The second sustained-release coating is carried out in a coating pan; (8) Gastric-soluble coating layer A coating: Gastric-soluble coating layer A coating is carried out in a coating pan.

[0041] Example 2 The difference between this embodiment and Embodiment 1 is that: the diameter of the sustained-release tablet is 12.5 mm, and the diameter of the three-layer tablet core is 11.5 mm; the thicknesses of the first shielding layer 1, the drug-containing layer 2, and the second shielding layer 3 are 3.0 mm, 3.0 mm, and 3.0 mm, respectively, with a thickness ratio of 1:1:1; the thickness of the first sustained-release coating layer 4 is 6 μm, and the thickness of the second sustained-release coating layer 5 is 0.9 mm.

[0042] Example 3 The difference between this embodiment and Embodiment 1 is that: the diameter of the sustained-release tablet is 11.0 mm, and the diameter of the three-layer tablet core is 10.0 mm; the thicknesses of the first shielding layer 1, the drug-containing layer 2, and the second shielding layer 3 are 3.5 mm, 2.5 mm, and 3.5 mm, respectively, with a thickness ratio of 1.4:1:1.4; the thickness of the first sustained-release coating layer 4 is 10 μm, and the thickness of the second sustained-release coating layer 5 is 0.8 mm.

[0043] Comparative Example Hydrocodone bitartrate chip (trade name: Hysingla ER, from Purdue Pharma LP, batch number: WR7B1) was used as a comparative example. Figure 2 As shown, the chip includes: a core layer 7, an outer shell layer 8 covering the core layer 7, and a gastrointestinal coating layer B 9 covering the outer shell layer 8.

[0044] The core layer 7 consists of 80% hydrocodone bitartrate, microcrystalline cellulose, polyoxyethylene, hydroxypropyl cellulose, and magnesium stearate; the outer shell layer 8 consists of 20% hydrocodone bitartrate, microcrystalline cellulose, polyoxyethylene, hydroxypropyl cellulose, and magnesium stearate; and the gastrosoluble coating layer B 9 consists of polyethylene glycol 3350, polysorbate 80, polyvinyl alcohol, talc, titanium dioxide, lake pigment, and ink.

[0045] Test Example 1: Tablet Hardness Test The three-layer tablet core coated with the first sustained-release coating layer in the example was tested before and after heat curing in step (6) of the preparation method using an HT-1 hardness tester (the hardness tester's measurement range is 0 to 80 kgf (kp)). The sustained-release tablet was placed in the tablet clamp with the top surface of the drug-containing layer parallel to the horizontal direction. The test was started, and the indenter was pushed forward at a uniform speed. The instrument locked the peak hardness at the moment the tablet broke. The test was repeated 5 times, and the average hardness was recorded. The results are shown in Table 2.

[0046] Table 2 Test Example 2 Dissolution Test Dissolution profiles for Examples 1-3 and the comparative examples were determined using USP apparatus I (basket method, 100 rpm) in 900 mL of various media, including enzyme-free simulated gastric juice (SGF) (pH 1.2), pH 4.5 acetate buffer, and pH 6.8 phosphate buffer. Results are as follows: Figures 3-6 As shown, compared to the comparative example, the tablets prepared in the examples achieved the effect of preventing abuse while their drug release was not affected. The tablets prepared in Examples 1-3 all achieved a 24-hour sustained release effect.

[0047] Test Example 3: Abuse Prevention Test 1. Physical abuse prevention test The tablets prepared in Examples 1-2 and the comparative hydrocodone bitartrate chips were ground for 5 min using a coffee machine to simulate the behavior of abusers obtaining drugs through physical grinding. After grinding, the particle size distribution and the recovery rate of the active pharmaceutical ingredient (API) were determined by sieving to evaluate the resistance of the two types of tablets to physical degradation. The processing method is as follows: A. Use a digital infrared thermometer to check the temperature of the coffee grinder (the area marked "KRUPS") to ensure it is below 30.0 ℃ and that there are no cracks in the lid.

[0048] B. Record the weight of the complete tablet.

[0049] C. Place a piece of black paper under the glass cutting plate to ensure that the materials being processed are highly visible and easy to collect when falling.

[0050] D. Using wire cutters, cut the tablets into 8 pieces as evenly as possible, then cut each piece in half, resulting in a total of 16 pieces. Collect any loose material in the coffee grinder lid during the cutting process.

[0051] E. Carefully transfer the cut pieces into the coffee grinder and securely attach the grinder lid.

[0052] F. Start the grinder every 15 seconds, let it stand for 30 seconds; repeat 20 times to achieve a total grinding time of 5 minutes.

[0053] G. Before removing the lid, let the powder stand for at least 3 minutes.

[0054] H. Record the weight of the empty, labeled, flashing bottles with caps.

[0055] I. Carefully collect the materials after the operation into the weighing boat.

[0056] J. Transfer the processed material to the scintillation bottle and cap it.

[0057] K. Record the weight of the material being handled and the scintillation bottle with its sealed cap.

[0058] L. Calculate the weight recovery rate: Weight recovery rate % = [Weight of labeled scintillation bottles and handling materials - Weight of empty labeled scintillation bottles] / Weight of intact flakes] × 100% M. Particle size analysis (analyzing the proportion of particles in each layer to the total recovered particles) and API recovery analysis (detecting the API content in each layer of particles) were performed. The experimental results are shown in Table 3: Table 3 Results of Physical Damage Resistance Tests Fine-sized particles smaller than 500 μm are the preferred choice for nasal inhalation abuse. As shown in Table 3 above, although the weight proportion of particles smaller than 500 μm in Examples 1-2 is higher than that in the comparative example, the API recovery rate of particles smaller than 500 μm is lower in Examples 1-2 than in the comparative example. That is, there is less abuseable API in fine-sized particles, resulting in better abuse prevention. The possible reasons for the above results are as follows: Since the chip packaging of the comparative example does not have a drug-free shielding layer design, the API and excipients are evenly distributed and are easily crushed. Once ground into fine-sized particles, these fine-sized particles actually contain API in proportion, resulting in a high measured API recovery content. The present invention, through the three-layer core structure design of "first shielding layer - drug-containing layer - second shielding layer", ensures that when the tablet is physically crushed, the main component of the fine-sized particles is the crushed, drug-free polymer material. Due to the "protection" of the polymer material or its own large particle characteristics, API is more retained in the crushed large particles, thereby effectively preventing nasal inhalation abuse and possessing good physical abuse prevention function.

[0059] 2. Anti-extraction abuse test The sustained-release tablets prepared in Examples 1-2 and the comparative hydrocodone bitartrate chip were subjected to an anti-extraction abuse test, as follows: A. Carefully transfer the intact sample or physically treated sample into a 500 mL dry flask.

[0060] B. Add 240 mL of the selected solvent using a layering method, and shake at 280 rpm for 30 minutes.

[0061] Level 1: Deionized water, room temperature; Category 2A: Vinegar, 0.2wt% baking soda, 40% v / v ethanol and carbonated beverages, at room temperature; Level 2B: Deionized water, boiling; Level 3A: 100% ethanol, 100% isopropanol, 100% acetone, 0.1N HCl and 0.1N NaOH, room temperature; Category 3B: Vinegar, 0.2wt% baking soda, 40% v / v ethanol and carbonated beverages, boiled; C. Transfer approximately 10 mL of the solution into a 15 mL centrifuge tube; D. Centrifuge the solution at 4700 rpm for 7 minutes; E. Collect 5.0 mL of supernatant and dilute with the appropriate diluent.

[0062] The sample was filtered through a 0.45 μm nylon membrane into a vial for HPLC analysis of the drug content. The test results are as follows: Table 4 Results of Anti-Abuse Test The above results show that the extraction rates of the sustained-release tablets prepared in Examples 1-2 in all the above-mentioned solvents are lower than those in the comparative examples. This proves that the present invention, through the three-layer core structure of "first shielding layer - drug-containing layer - second shielding layer", can form a high-viscosity gel layer after the shielding layer comes into contact with solvent. This can effectively resist the penetration and erosion of various commonly used extraction solvents such as water, acidic media, and ethanol solutions, significantly reducing the risk of rapid extraction of drug active ingredients. Thus, it has a significant advantage in preventing the abuse of solvent extraction for injection, oral administration, etc.

[0063] Although the embodiments disclosed in this utility model are as described above, the content described is only for the purpose of facilitating understanding of this utility model and is not intended to limit this utility model. Any person skilled in the art to which this utility model pertains may make any modifications and changes in the form and details of the implementation without departing from the spirit and scope disclosed in this utility model, but the patent protection scope of this utility model shall still be defined by the appended claims.

Claims

1. A sustained-release tablet with anti-abuse function, characterized in that, include: A first shielding layer, a drug-containing layer, and a second shielding layer; the drug-containing layer has opposing top and bottom surfaces, and a side peripheral surface connecting the top and bottom surfaces; the first and second shielding layers respectively cover the top and bottom surfaces of the drug-containing layer, together forming a three-layer core that sandwiches the drug-containing layer in the middle and exposes the side peripheral surface of the drug-containing layer; wherein the drug-containing layer contains an abused drug and pharmaceutically acceptable excipients, and both the first and second shielding layers are polymer material layers; and At least one sustained-release coating layer and a gastrosoluble coating layer are sequentially coated on the surface of the three-layer tablet core.

2. The sustained-release tablet according to claim 1, characterized in that, In the three-layer core, the thickness ratio of the first shielding layer, the drug-containing layer, and the second shielding layer is 0.8 to 1.5 : 1 : 0.8 to 1.

5.

3. The sustained-release tablet according to claim 1, characterized in that, The diameter of the sustained-release tablets is 9 mm to 17 mm.

4. The sustained-release tablet according to claim 1, characterized in that, The diameter of the three-layer core is 8 mm to 16 mm.

5. The sustained-release tablet according to claim 1, characterized in that, In the three-layer core, the thickness of the first shielding layer and the second shielding layer is ≥ 2 mm, and the thickness of the drug-containing layer is 2.5 mm to 3.5 mm.

6. The sustained-release tablet according to any one of claims 1 to 5, characterized in that, The polymer material layer is composed of a thermoplastic polymer material with water-swellable properties.

7. The sustained-release tablet according to claim 6, characterized in that, In the polymer material layer, the water-swellable thermoplastic polymer material is a continuous matrix phase that is melted and then solidified.

8. The sustained-release tablet according to claim 6, characterized in that, The polymer material layer contains a lubricant.

9. The sustained-release tablet according to any one of claims 1 to 5, characterized in that, The sustained-release tablet has a first sustained-release coating layer, a second sustained-release coating layer, and a gastrosoluble coating layer sequentially coated on the surface of the three-layer tablet core.

10. The sustained-release tablet according to claim 9, characterized in that, The thickness ratio of the first sustained-release coating layer to the second sustained-release coating layer is 1:50 to 350.

11. The sustained-release tablet according to claim 9, characterized in that, The thickness of the first sustained-release coating layer is 3 μm to 12 μm, and the thickness of the second sustained-release coating layer is 0.7 mm to 1.0 mm.

12. The sustained-release tablet according to any one of claims 1 to 5, characterized in that, The cross-sectional shape of the sustained-release tablet parallel to the top surface of the drug-containing layer is circular, elliptical, triangular, rhomboid, hexagonal, or butterfly-shaped.

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