Bilayer capsules for intestinal targeted drug delivery

Abstract

This utility model relates to the field of capsule technology and discloses a double-layer capsule for intestinal targeted drug delivery, comprising: an outer layer and an inner layer, the inner layer being disposed inside the outer layer, and a connecting sealing layer disposed on the outside of the inner layer. The outer layer has an outer thickness of 0.1–0.5 mm. The inner layer employs microporous membrane controlled-release technology, has a thickness of 0.5–2 mm, and includes a microporous membrane layer made of ethyl cellulose. The microporous membrane layer has micropores with a diameter of 0.1–10 micrometers on its outer surface. The connecting sealing layer is disposed between the outer and inner layers. The outer layer includes a hydroxypropyl methylcellulose phthalate shell, and the inner cavity of the inner layer has an inner liner layer, the inner cavity of which has an inner plate. This double-layer capsule for intestinal targeted drug delivery can achieve continuous drug release in the intestine, ensuring that an effective drug concentration is maintained in the intestine, thereby acting more effectively on the intestinal lesion site and improving the therapeutic effect on intestinal diseases.

Description

Technical Field

[0001] This utility model relates to the field of capsule technology, specifically to a double-layer capsule for intestinal targeted drug delivery. Background Technology

[0002] In the current pharmaceutical field, many drugs need to exert their effects in specific locations within the intestines; however, traditional capsule formulations have several drawbacks. On the one hand, ordinary capsules, once in the stomach, are easily affected by the acidic environment, leading to premature drug release. This can not only irritate the gastric mucosa but also cause the drug to be partially consumed before reaching the intestines, failing to guarantee an effective concentration within the intestines. On the other hand, while some enteric-coated capsules can avoid drug release in the stomach, their structural and material limitations make it difficult to precisely control the release time and rate of the drug in different parts of the intestines, affecting therapeutic efficacy. For example, in treating intestinal diseases such as enteritis and intestinal flora imbalance, it is necessary for the drug to accumulate at high concentrations and exert a sustained effect in specific areas of the intestines, a requirement that current capsule formulations struggle to meet. Utility Model Content

[0003] To address the shortcomings of existing technologies, this invention provides a bilayer capsule for intestinal targeted drug delivery, thereby solving the aforementioned technical problems.

[0004] To achieve the above objectives, the present invention provides the following technical solution: a bilayer capsule for intestinal targeted drug delivery, comprising: an outer layer and an inner layer, wherein the inner layer is disposed inside the outer layer, and a connecting sealing layer is disposed outside the inner layer, the outer thickness of the outer layer is 0.1 to 0.5 mm, the inner layer adopts microporous membrane controlled release technology, the thickness of the inner layer is 0.5 to 2 mm, the inner layer includes a microporous membrane layer, the microporous membrane layer is ethyl cellulose, and micropores are formed on the outer side of the microporous membrane layer;

[0005] The micropores have a diameter of 0.1-10 micrometers. A sealing layer is positioned between the outer and inner layers. The outer layer consists of a hydroxypropyl methylcellulose phthalate shell, and the inner layer has an inner liner within its cavity. The inner liner has an inner plate within its cavity, and the inner cavity of the inner layer is filled with the drug. Working principle: After oral administration, the hydroxypropyl methylcellulose phthalate shell remains stable in the acidic environment of the stomach, protecting the drug in the inner layer from premature release and preventing drug irritation of the gastric mucosa or consumption in the stomach. As the capsule enters the weakly alkaline environment of the intestine, the outer layer rapidly dissolves, exposing the inner ethylcellulose microporous membrane layer. The drug is released at a constant rate through the 0.1-10 micrometer micropores in the microporous membrane layer.

[0006] This technology achieves precise drug release at specific sites in the intestine, avoiding efficacy loss and gastric mucosal irritation caused by premature release in the stomach. Simultaneously, microporous membrane controlled-release technology allows for continuous drug release within the intestine, with a release time designed to be 6–24 hours, ensuring effective drug concentration in the intestine and improving the treatment effect for intestinal diseases. The connecting sealing layer is made of polyethylene glycol, with a thickness of 0.05–0.2 mm. Working principle: The polyethylene glycol in the connecting sealing layer remains stable in the acidic environment of the stomach, firmly connecting the outer and inner layers and preventing separation in the stomach. Upon entering the intestinal environment, the polyethylene glycol softens rapidly without disrupting the overall connection structure between the outer and inner layers, and does not affect the controlled-release function of the inner layer after the outer layer dissolves. This ensures a tight connection between the outer and inner layers during storage, transportation, and residence in the stomach, preventing drug leakage, while not hindering drug release in the intestine, guaranteeing the stability and reliability of the drug administration process.

[0007] The inner liner is a biodegradable pharmaceutical film made of polylactic acid (PLA), and its inner wall has a textured surface. The PLA in the liner gradually biodegrades in the intestines and leaves no residue in the body. The textured surface increases the contact area with the drug, allowing the drug to be stably packed between the liner and the inner membrane, preventing displacement or aggregation of the drug during capsule movement. This ensures medication safety and avoids the risk of accumulation in the body caused by non-degradable materials. Furthermore, it ensures uniform drug distribution before release, laying the foundation for stable release through the inner microporous membrane and preventing release rate fluctuations caused by drug displacement.

[0008] Preferably, the inner panel has a circular structure, is made of cross-linked polyvinyl chloride, and has water absorption and swelling properties.

[0009] After the cross-linked polyvinyl chloride in the inner plate enters the intestine, it absorbs water in the intestine and swells. The swollen inner plate can appropriately expand the microporous membrane layer of the inner layer, keeping the micropores on the microporous membrane layer open and preventing the micropores from being blocked due to factors such as capsule deformation.

[0010] This ensures that the drug can be released smoothly through the micropores, avoiding drug release obstruction due to micropore blockage, and ensuring that the drug release rate meets the design requirements. At the same time, cross-linked povidone has good biocompatibility and can be safely excreted from the body without toxic side effects.

[0011] Preferably, the drug is a sustained-release microsphere, and the particle size of the sustained-release microsphere is 50-200 micrometers.

[0012] The sustained-release microcapsules of the drug itself have certain sustained-release characteristics. Combined with the ethyl cellulose microporous membrane control-release technology of the inner layer, a "dual control-release" can be formed.

[0013] The particle size of the sustained-release microcapsules is 50-200 micrometers, which matches the pore diameter of the inner microporous membrane layer, which is 0.1-10 micrometers. This not only facilitates the stable filling of the microcapsules into the inner cavity, but also ensures the slow release of the drug in the microcapsules through the micropores.

[0014] This further prolongs the drug release time in the intestine, enabling continuous administration for 6 to 24 hours, avoiding the "sudden release" phenomenon in the intestine, and maintaining the drug concentration in the intestine within the therapeutic window, thereby improving the therapeutic effect while reducing local intestinal irritation caused by excessively high drug concentrations.

[0015] Preferably, the outer hydroxypropyl methylcellulose phthalate shell is HPMCP55, and the outer surface of the outer layer is coated with an anti-adhesion coating made of silicon dioxide with a thickness of 0.01 to 0.05 mm.

[0016] The HPMCP55 model has excellent enteric coating properties and strong tolerance to gastric acid. It is completely insoluble in the acidic environment of gastric acid at pH 1.5-3.5, but dissolves rapidly only in the weakly alkaline environment of the intestine at pH 7.0-8.0, allowing for precise control of the dissolution timing of the outer layer. The silica anti-adhesion coating on the outer surface reduces friction between capsules and prevents them from sticking together during storage or filling.

[0017] On the one hand, it ensures that the outer layer dissolves precisely in the intestines, avoiding premature release of the drug in the stomach and ensuring targeting; on the other hand, it solves the problem of capsule adhesion, facilitating filling operations during production and subsequent storage management. Moreover, the silica coating is thin and will not affect the enteric properties of the outer layer or the dissolution rate in the intestines.

[0018] Compared with the prior art, this invention provides a bilayer capsule for intestinal targeted drug delivery, which has the following beneficial effects:

[0019] This bilayer capsule for targeted intestinal drug delivery utilizes a specific outer shell material that allows it to remain stable in the acidic environment of the stomach after oral administration. This effectively protects the drug in the inner layer from premature release, preventing irritation to the gastric mucosa and loss of efficacy due to drug consumption in the stomach. As the capsule moves into the weakly alkaline environment of the intestine with peristalsis, the outer layer dissolves rapidly, exposing the microporous inner layer. The drug can then be released at a stable rate through the micropores in the inner membrane. Simultaneously, the microporous membrane controlled-release technology used in the inner layer enables continuous drug release within the intestine, ensuring a consistently effective drug concentration and thus more effectively targeting intestinal lesions, enhancing the therapeutic effect on intestinal diseases. Attached Figure Description

[0020] Figure 1 This is a front view of the present utility model;

[0021] Figure 2 This is a partial sectional view of the present invention.

[0022] In the diagram: 1. Outer layer; 2. Inner layer; 3. Connecting and sealing layer; 4. Inner lining layer; 5. Inner plate; 6. Drug body. Detailed Implementation

[0023] The technical solutions of the present utility model will be clearly and completely described below with reference to the accompanying drawings of the embodiments. Obviously, the described embodiments are only some embodiments of the present utility model, and not all embodiments. Based on the embodiments of the present utility model, all other embodiments obtained by those of ordinary skill in the art without creative effort are within the protection scope of the present utility model.

[0024] This utility model provides a technical solution, please refer to [link / reference]. Figure 1 -and Figure 2 A bilayer capsule for intestinal targeted drug delivery includes: an outer layer 1 and an inner layer 2, the inner layer 2 being disposed inside the outer layer 1, and a connecting sealing layer 3 being disposed on the outside of the inner layer 2. The outer thickness of the outer layer 1 is 0.1 to 0.5 mm, the inner layer 2 employs microporous membrane controlled release technology, the thickness of the inner layer 2 is 0.5 to 2 mm, the inner layer 2 includes a microporous membrane layer, the microporous membrane layer is ethyl cellulose, and micropores are formed on the outside of the microporous membrane layer;

[0025] The micropores have a diameter of 0.1-10 micrometers. A sealing layer 3 is disposed between the outer layer 1 and the inner layer 2. The outer layer 1 includes a hydroxypropyl methylcellulose phthalate shell. The inner cavity of the inner layer 2 is provided with an inner liner 4, and the inner cavity of the inner liner 4 is provided with an inner plate 5. The inner cavity of the inner layer 2 is filled with the drug 6. Working principle: After oral administration, the hydroxypropyl methylcellulose phthalate shell of the outer layer 1 remains stable in the acidic environment of the stomach, which can protect the drug 6 in the inner layer 2 from premature release, avoiding drug irritation of the gastric mucosa or consumption in the stomach.

[0026] As the capsule enters the weakly alkaline intestinal environment (pH 7.0-8.0), the outer layer 1 dissolves rapidly, exposing the inner layer 2, an ethyl cellulose microporous membrane. The drug 6 is then released at a constant rate through the 0.1-10 micrometer pores in the microporous membrane.

[0027] It enables precise drug release at specific sites in the intestine, avoiding drug efficacy loss and gastric mucosal irritation caused by premature release in the stomach. At the same time, the microporous membrane controlled-release technology allows for continuous drug release in the intestine, with the release time designed to be 6 to 24 hours, ensuring the effective drug concentration in the intestine and improving the treatment effect of intestinal diseases.

[0028] The sealing layer 3 is made of polyethylene glycol, and its thickness is 0.05–0.2 mm. Working principle: The polyethylene glycol in the sealing layer 3 remains stable in the acidic environment of the stomach, firmly connecting the outer layer 1 and the inner layer 2, preventing them from separating in the stomach. Upon entering the intestinal environment, the polyethylene glycol softens rapidly without damaging the overall connection structure between the outer layer 1 and the inner layer 2, and does not affect the controlled-release function of the inner layer 2 after the outer layer 1 dissolves.

[0029] To ensure that the outer layer 1 and inner layer 2 are tightly connected during storage, transportation and residence in the stomach, drug leakage is prevented, and drug release is not hindered in the intestine, thus ensuring the stability and reliability of the drug administration process.

[0030] The inner liner 4 is a biodegradable pharmaceutical film made of polylactic acid, and the inner wall of the inner liner 4 is textured with concave and convex patterns.

[0031] The polylactic acid in the inner liner 4 can be gradually biodegraded in the intestine and will not remain in the body; the texture of the inner wall can increase the contact area with the drug 6, so that the drug 6 can be stably filled between the inner liner 4 and the inner plate 5, and prevent the drug 6 from shifting or aggregating during the movement of the capsule.

[0032] On the one hand, it ensures the safety of medication and avoids the risk of in vivo accumulation caused by non-degradable materials; on the other hand, it ensures that the drug 6 is evenly distributed before release, laying the foundation for stable release through the inner layer 2 microporous membrane layer and avoiding fluctuations in the release rate caused by the displacement of the drug 6.

[0033] The inner panel 5 has a circular structure and is made of cross-linked polyvinyl ketone. The inner panel 5 also has the property of absorbing water and swelling.

[0034] After the cross-linked polyvinyl chloride of the inner plate 5 enters the intestine, it absorbs water in the intestine and expands. The expanded inner plate 5 can appropriately stretch the microporous membrane layer of the inner layer 2, so that the micropores on the microporous membrane layer remain open and the micropores are prevented from being blocked due to factors such as capsule deformation.

[0035] This ensures that drug 6 can be released smoothly through micropores, avoiding drug release obstruction due to micropore blockage, and ensuring that the drug release rate meets the design requirements. At the same time, cross-linked povidone has good biocompatibility and can be safely excreted from the body without toxic side effects.

[0036] Drug body 6 is a sustained-release microsphere with a particle size of 50-200 micrometers.

[0037] The sustained-release microgranules of drug body 6 have certain sustained-release characteristics. Combined with the ethyl cellulose microporous membrane controlled-release technology of inner layer 2, a "dual controlled-release" can be formed.

[0038] The particle size of the sustained-release microcapsules is 50-200 micrometers, which matches the pore diameter of the inner layer 2 microporous membrane layer, which is 0.1-10 micrometers. This not only facilitates the stable filling of the microcapsules into the inner cavity of the inner layer 2, but also ensures that the drug in the microcapsules is slowly released through the micropores.

[0039] This further prolongs the drug release time in the intestine, enabling continuous administration for 6 to 24 hours, avoiding the "sudden release" phenomenon in the intestine, and maintaining the drug concentration in the intestine within the therapeutic window, thereby improving the therapeutic effect while reducing local intestinal irritation caused by excessively high drug concentrations.

[0040] The outer layer 1 has a hydroxypropyl methylcellulose phthalate shell of model HPMCP55, and the outer surface of the outer layer 1 is coated with an anti-adhesion coating made of silicon dioxide with a thickness of 0.01 to 0.05 mm.

[0041] The HPMCP55 model has excellent enteric coating properties and strong tolerance to gastric acid. It is completely insoluble in the acidic environment of gastric acid at pH 1.5-3.5, and dissolves rapidly only in the weakly alkaline environment of the intestine at pH 7.0-8.0, allowing for precise control of the dissolution timing of the outer layer 1. The silica anti-adhesion coating on the outer surface of the outer layer 1 can reduce the friction between capsules and prevent capsules from sticking together during storage or filling.

[0042] On the one hand, it ensures that the outer layer 1 dissolves precisely in the intestine, avoiding premature release of the drug in the stomach and ensuring targeting; on the other hand, it solves the problem of capsule adhesion, facilitating filling operations and subsequent storage management during the production process. Moreover, the silica coating is thin and will not affect the enteric properties of the outer layer 1 or its dissolution rate in the intestine.

[0043] It should be noted that, in this document, relational terms such as "first" and "second" are used only 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 process, method, article, or apparatus.

[0044] Although embodiments of the present invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made to these embodiments without departing from the principles and spirit of the present invention, the scope of which is defined by the appended claims and their equivalents.

Claims

1. A bilayer capsule for intestinal targeted drug delivery, comprising: The outer layer (1) and the inner layer (2) are disposed inside the outer layer (1). The inner layer (2) is characterized in that: a connecting sealing layer (3) is disposed on the outside of the inner layer (2), the outer thickness of the outer layer (1) is 0.1 to 0.5 mm, the inner layer (2) adopts microporous membrane controlled release technology, the thickness of the inner layer (2) is 0.5 to 2 mm, the inner layer (2) includes a microporous membrane layer, the microporous membrane layer is ethyl cellulose, micropores are opened on the outside of the microporous membrane layer, the micropore diameter is 0.1-10 micrometers, the connecting sealing layer (3) is disposed between the outer layer (1) and the inner layer (2), the outer layer (1) includes a hydroxypropyl methylcellulose phthalate shell, the inner cavity of the inner layer (2) is provided with an inner liner (4), the inner cavity of the inner liner (4) is provided with an inner plate (5), and the inner cavity of the inner layer (2) is filled with a drug body (6).

2. The bilayer capsule for intestinal targeted drug delivery according to claim 1, characterized in that: The connecting sealing layer (3) is made of polyethylene glycol, and the thickness of the connecting sealing layer (3) is 0.05 to 0.2 mm.

3. The bilayer capsule for intestinal targeted drug delivery according to claim 2, characterized in that: The inner liner (4) is a biodegradable pharmaceutical film made of polylactic acid, and the inner wall of the inner liner (4) is provided with a textured surface.

4. The bilayer capsule for intestinal targeted drug delivery according to claim 1, characterized in that: The inner plate (5) has a circular structure and is made of cross-linked polyvinyl ketone. The inner plate (5) has water absorption and swelling properties.

5. The bilayer capsule for intestinal targeted drug delivery according to claim 1, characterized in that: The drug body (6) is a sustained-release microsphere, and the particle size of the sustained-release microsphere is 50-200 micrometers.

6. The bilayer capsule for intestinal targeted drug delivery according to claim 1, characterized in that: The outer layer (1) has a hydroxypropyl methylcellulose phthalate shell of model HPMCP55, and the outer surface of the outer layer (1) is coated with an anti-adhesion coating. The anti-adhesion coating is made of silicon dioxide and has a thickness of 0.01 to 0.05 mm.

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