Mesalazine oral controlled-release pharmaceutical composition and preparation method thereof

Abstract

The invention belongs to the technical field of mesalazine controlled-release preparations, and particularly relates to a mesalazine oral controlled-release pharmaceutical composition and a preparation method thereof.The mesalazine oral controlled-release pharmaceutical composition comprises a tablet core part and a coating part and is characterized in that the outer layer of the tablet core part is wrapped with the coating part, the tablet core part is composed of mesalazine and auxiliary materials, and the auxiliary materials are added into the tablet core part. The auxiliary material components comprise a matrix material, a filler, an adhesive and a lubricant, and the coating part is composed of an acid-resistant material, a plasticizer and a light shielding agent. According to the tablet core particle screening device, dried tablet core particles can be rapidly screened through the arranged vibration screening assembly, power of the vibration screening assembly can be transmitted through the arranged transmission assembly so that the transverse moving screening assembly can be driven, and the phenomenon that screening holes are blocked can be effectively reduced through the arranged transverse moving screening assembly; and therefore, the screening efficiency of the tablet core particles and the subsequent production efficiency can be improved.

Description

Technical Field

[0001] The invention belongs to the technical field of mesalazine controlled-release preparations, and in particular relates to a mesalazine oral controlled-release pharmaceutical composition and a preparation method thereof. Background Art

[0002] Mesalazine is a 5-aminosalicylic acid, which is mainly used to treat inflammatory bowel diseases, such as ulcerative colitis and Crohn's disease. Mesalazine can inhibit the synthesis of prostaglandins and the formation of leukotrienes that cause inflammation, and has a significant anti-inflammatory effect on inflammation of the intestinal mucosa. It can relieve symptoms such as congestion, edema and ulcers of the intestinal mucosa. The mesalazine oral controlled-release pharmaceutical composition is a special pharmaceutical preparation, which is mainly composed of mesalazine as the active ingredient and a variety of excipients. This composition is mainly in the form of oral dosage forms, such as tablets or capsules, and the drug is released in a predetermined manner in the gastrointestinal tract through precise formulation technology.

[0003] Regarding the granulation device required in the production process of mesalazine oral controlled-release pharmaceutical composition, the existing technology is not efficient in screening the dried particles, which will affect the processing efficiency of the entire production line. At the same time, when screening, the traditional screening method does not take into account the problem that large particles will accumulate in the sieve holes, thereby reducing the screening efficiency. Therefore, when screening, not only vibration screening should be performed, but other screening measures should also be used to cooperate in order to achieve more efficient screening. Summary of the invention

[0004] The purpose of the present invention is to address the problem of low screening efficiency for dried core particles and to provide a mesalazine oral controlled-release pharmaceutical composition and a preparation method thereof that can efficiently screen dried core particles.

[0005] To achieve the above object, the present invention adopts the following technical scheme: a mesalamine oral controlled-release pharmaceutical composition, comprising a core part and a coating part, characterized in that the coating part is wrapped in the outer layer of the core part, the core part is composed of mesalamine and auxiliary material components, the auxiliary material components include matrix material, filler, adhesive and lubricant, the coating part is composed of acid-resistant material, plasticizer and light-shielding agent, the matrix material is a hydrophilic matrix material, the ingredients contained therein include hydroxypropyl methylcellulose, sodium carboxymethyl cellulose and carbomer, and the acid-resistant material can be any one of the polymers and copolymers of acrylic acid and methacrylic acid.

[0006] Preferably, the mesalazine accounts for 70% of the mass proportion of the tablet core, the matrix material accounts for 20% of the mass proportion of the tablet core, the hydroxypropyl methylcellulose in the matrix material accounts for 13% of the mass proportion of the tablet core, the sodium carboxymethyl cellulose in the matrix material accounts for 5% of the mass proportion of the tablet core, the carbomer in the matrix material accounts for 2% of the mass proportion of the tablet core, the filler accounts for 6% of the mass proportion of the tablet core, the binder accounts for 3% of the mass proportion of the tablet core, the lubricant accounts for 1% of the mass proportion of the tablet core, and the mass ratio of the core part to the coating part is 5:1-20:1.

[0007] Preferably, the acid-resistant material accounts for 70% of the coating portion by mass, the plasticizer accounts for 25% of the coating portion by mass, and the light-shielding agent accounts for 5% of the coating portion by mass.

[0008] Preferably, the material of the filler is microcrystalline cellulose or lactose, the material of the binder is povidone, and the material of the lubricant is magnesium stearate.

[0009] Preferably, the material of the plasticizer is triethyl citrate or phthalate, and the material of the opacifier is titanium dioxide.

[0010] A method for preparing a mesalazine oral controlled-release pharmaceutical composition, the specific preparation method is as follows:

[0011] S1: First, prepare the tablet core, mix mesalazine or its pharmaceutically acceptable salt or its solvate with a hydrophilic matrix material, then add an appropriate amount of a binder, a lubricant and a filler, and prepare the tablet core by a wet granulation process;

[0012] S2: Then, the prepared particles are dried using a drying device, and particles that meet the requirements are screened out using a granulation device to remove particles that are too large or too small;

[0013] S3: After the granules are uniformly mixed with an appropriate amount of lubricant, the granules are pressed into tablets using a rotary tablet press, and the pressed tablets are coated. A coating liquid containing an acid-resistant material is evenly sprayed on the surface of the tablet core using a coating device to form a coating layer;

[0014] S4: curing the coated tablets to enhance the stability of the coating, thereby obtaining a mesalazine oral controlled-release pharmaceutical composition with a double-layer tablet structure.

[0015] The preparation process of the above-mentioned mesalazine oral controlled-release pharmaceutical composition also involves a granulation device, including a body, the upper surface of which is fixedly connected to two supporting plates, the upper surfaces of the two supporting plates are slidably connected to a moving seat, a connecting plate is fixedly connected between adjacent side walls of the two moving seats, and the inner bottom surface of the body is fixedly provided with a collecting box;

[0016] The grain-sizing mechanism comprises a vibration screening component, a transmission component and a transversely movable screening component, the vibration screening component comprises a No. 1 fixed plate fixedly connected to the side walls of the two movable seats, a screen box is arranged in the body, and a No. 2 fixed plate is fixedly connected to the side walls of the two sides of the screen box, and two springs are fixedly connected between the upper surfaces of the two No. 2 fixed plates and the bottom surfaces of the two No. 1 fixed plates, the side walls of the body are fixedly connected to a motor through a bracket, the output end of the motor is fixedly connected to a rotating shaft, the rotating shaft is rotatably connected to the inner wall of the body through a bearing, and the side end of the rotating shaft is fixedly connected to a cam.

[0017] Preferably, the transmission assembly includes a load-bearing bracket fixedly connected to the side wall of the body, a reciprocating threaded rod is provided on the side of the body, the reciprocating threaded rod is rotatably connected to the side wall of the load-bearing bracket through a bearing, a driving wheel is fixedly connected to the circumference of the rotating shaft, and a driven wheel is fixedly connected to the circumference of the reciprocating threaded rod, and a belt is sleeved between the driving wheel and the driven wheel.

[0018] Preferably, the laterally movable screening assembly includes a nut threadedly connected to a reciprocating threaded rod, side walls on both sides of the nut are fixedly connected to force plates, side walls of the two force plates are fixedly connected to connecting rods, side ends of the two connecting rods are fixedly connected to the side walls of adjacent movable seats, the upper surface of the nut is fixedly connected to a guide plate, side walls of the guide plate are fixedly connected to guide rods, and the guide rods penetrate and are slidably connected to the side walls of the supporting bracket.

[0019] Compared with the prior art, the advantages of the present invention are:

[0020] 1. The present invention provides a vibration screening component, which can quickly screen the dried core particles when screening the core particles required for the mesalazine oral controlled-release pharmaceutical composition. The dried core particles are placed in a screen box, and the vibration screening component causes the screen box to vibrate, which is beneficial to improving the screening speed and efficiency.

[0021] 2. The present invention provides a transmission component. When screening the core particles required for the mesalazine oral controlled-release pharmaceutical composition, the transmission component can transmit the power of the vibration screening component, thereby driving the lateral movement screening component. Only one power output is used, and multiple functions can be realized. While improving the practicality of the device, it is also beneficial to reduce the use cost of the device.

[0022] 3. The present invention sets a lateral moving screening component. When screening the tablet core particles required for the mesalazine oral controlled-release pharmaceutical composition, it cooperates with a vibrating screening component to make the screen box vibrate while also enabling it to move back and forth left and right. In this way, the influence of large-sized particles on the screen holes can be reduced, and the occurrence of screen hole blockage can be effectively reduced, which is beneficial to improving the screening efficiency of the tablet core particles and the subsequent production efficiency. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] Figure 1 It is a schematic flow diagram of the preparation method of the present invention;

[0024] Figure 2 It is a three-dimensional structural schematic diagram of the present invention;

[0025] Figure 3 It is a three-dimensional structural schematic diagram of another viewing angle of the present invention;

[0026] Figure 4 is a schematic diagram of the three-dimensional structure of the present invention from another viewing angle;

[0027] Figure 5 It is a three-dimensional structural schematic diagram of the present invention from another viewing angle.

[0028] In the figure, 1 is a machine body; 2 is a bearing plate; 3 is a moving seat; 4 is a connecting plate; 5 is a collecting box; 6 is a No. 1 fixing plate; 7 is a screen box; 8 is a No. 2 fixing plate; 9 is a spring; 10 is a motor; 11 is a rotating shaft; 12 is a cam; 13 is a bearing bracket; 14 is a reciprocating threaded rod; 15 is a driving wheel; 16 is a driven wheel; 17 is a belt; 18 is a nut; 19 is a force plate; 20 is a connecting rod; 21 is a guide plate; 22 is a guide rod. DETAILED DESCRIPTION

[0029] The following examples are for illustrative purposes only and are not intended to limit the scope of the present invention.

[0030] A mesalazine oral controlled-release pharmaceutical composition comprises a tablet core part and a coating part, wherein the coating part is wrapped in the outer layer of the tablet core part, the tablet core part is composed of mesalazine and auxiliary material components, the auxiliary material components include a matrix material, a filler, an adhesive and a lubricant, the coating part is composed of an acid-resistant material, a plasticizer and a light-shielding agent, the matrix material is a hydrophilic matrix material, and the components contained therein include hydroxypropyl methylcellulose, sodium carboxymethyl cellulose and carbomer, the acid-resistant material can be any one of a polymer and a copolymer of acrylic acid and methacrylic acid, the mass proportion of mesalazine in the tablet core part is 70%, the mass proportion of the matrix material in the tablet core part is 20%, the mass proportion of hydroxypropyl methylcellulose in the matrix material in the tablet core part is 13%, and the matrix material The mass ratio of sodium carboxymethyl cellulose in the material is 5% of the core part, the mass ratio of carbomer in the matrix material is 2% of the core part, the filler is 6% of the core part, the binder is 3% of the core part, the lubricant is 1% of the core part, the mass ratio of the core part to the coating part is 5:1-20:1, the acid-resistant material is 70% of the coating part, the plasticizer is 25% of the coating part, the opacifier is 5% of the coating part, the filler is microcrystalline cellulose or lactose, the binder is povidone, the lubricant is magnesium stearate, the plasticizer is triethyl citrate or phthalate, and the opacifier is titanium dioxide.

[0031] like Figure 1-Figure 5 As shown, a method for preparing a mesalazine oral controlled-release pharmaceutical composition, the specific preparation method is as follows:

[0032] S1: First, prepare the core part of the tablet by mixing mesalazine or its pharmaceutically acceptable salt or its solvate with the hydrophilic matrix material. It is recommended to mix at room temperature, and the temperature should be controlled at 20-25°C. Meanwhile, the ideal pH environment of the entire mixing process should be close to neutral, and the pH should be controlled between 6-8. After the mixing is completed, add an appropriate amount of adhesive, lubricant and filler, and prepare the core of the tablet by wet granulation process;

[0033] S2: Then, the prepared granules are dried using a drying device, the drying temperature is controlled at 40-60°C, and the drying time is determined according to the moisture content of the granules and the efficiency of the drying equipment, generally 20-60 minutes, so that the moisture content of the granules is reduced to 2%-5%. After the drying is completed, the granules that meet the requirements are screened out through a granulation device, and the oversized or undersized granules are removed;

[0034] S3: After the granules are uniformly mixed with an appropriate amount of lubricant, the granules are pressed into tablets using a rotary tablet press, and the pressed tablets are coated. A coating liquid containing an acid-resistant material is evenly sprayed on the surface of the tablet core using a coating device to form a coating layer;

[0035] S4: curing the coated tablets to enhance the stability of the coating, thereby obtaining a mesalazine oral controlled-release pharmaceutical composition with a double-layer tablet structure.

[0036] The preparation process of the above-mentioned mesalazine oral controlled-release pharmaceutical composition also involves a granulation device, including a body 1, two supporting plates 2 are fixedly connected to the upper surface of the body 1, and the upper surfaces of the two supporting plates 2 are slidably connected to a moving seat 3, and a connecting plate 4 is fixedly connected between the adjacent side walls of the two moving seats 3. The inner bottom surface of the body 1 is fixedly provided with a collecting box 5, a granulation mechanism, and a sorting mechanism includes a vibration screening component, a transmission component and a transversely movable screening component. The vibration screening component includes a No. 1 fixed plate 6 fixedly connected to the side walls of the two moving seats 3, a screen box 7 is provided in the body 1, and the side walls on both sides of the screen box 7 are fixedly connected to a No. 2 fixed plate 8, and two springs 9 are fixedly connected between the upper surfaces of the two No. 2 fixed plates 8 and the bottom surfaces of the two No. 1 fixed plates 6. The side wall of the body 1 is fixedly connected to a motor 10 through a bracket, and the output end of the motor 10 is fixedly connected to a rotating shaft 11, and the rotating shaft 11 is rotatably connected to the inner wall of the body 1 through a bearing. The side end of the rotating shaft 11 is fixedly connected with a cam 12, the transmission assembly includes a bearing bracket 13 fixedly connected to the side wall of the body 1, a reciprocating threaded rod 14 is provided on the side of the body 1, and the reciprocating threaded rod 14 is rotatably connected to the side wall of the bearing bracket 13 through a bearing, a driving wheel 15 is fixedly connected to the circumference of the rotating shaft 11, and a driven wheel 16 is fixedly connected to the circumference of the reciprocating threaded rod 14, and a belt 17 is sleeved between the driving wheel 15 and the driven wheel 16, and the transverse moving screening assembly includes a nut 18 threadedly connected to the reciprocating threaded rod 14, and the side walls of the nut 18 are fixedly connected with a force plate 19, and the side walls of the two force plates 19 are fixedly connected with a connecting rod 20, and the side ends of the two connecting rods 20 are fixedly connected to the side walls of the adjacent moving seats 3, and the upper surface of the nut 18 is fixedly connected with a guide plate 21, and the side wall of the guide plate 21 is fixedly connected with a guide rod 22, and the guide rod 22 penetrates and is slidably connected to the side wall of the bearing bracket 13.

[0037] The working principle of the present invention is as follows:

[0038] When screening the dried tablet core particles, the tablet core particles to be screened are poured into the screen box 7, and then the motor 10 is started. The motor 10 will drive the rotating shaft 11 to rotate, and the rotation of the rotating shaft 11 will drive the cam 12 to rotate eccentrically. The side wall of the cam 12 fits with the bottom surface of the screen box 7. There are no sieve holes around the area where the cam 12 is vertically projected to the bottom surface of the screen box 7, so as to prevent the tablet core particles from falling into the space between the cam 12 and the screen box 7 and being damaged. When the cam 12 rotates eccentrically, it will periodically push the screen box 7 upward for a short distance, and then under the action of multiple springs 9, the screen box 7 will vibrate, so that the screen box 7 can quickly screen the tablet core particles inside and screen out the smaller particles.

[0039] When the rotating shaft 11 rotates, it will drive the driving wheel 15 to rotate, and then drive the driven wheel 16 and the reciprocating threaded rod 14 to rotate through the transmission of the belt 17. When the reciprocating threaded rod 14 rotates, the nut 18 will be threadedly engaged with the reciprocating threaded rod 14 under the restriction of the guide plate 21 and the guide rod 22, and then it will reciprocate left and right along the reciprocating threaded rod 14. The nut 18 drives the moving seat 3 and the connecting plate 4 to move through two force plates 19 and two connecting rods 20. The movement of the two moving seats 3 and the connecting plate 4 will drive the screen box 7 to move. Only one power output is used, so that the screen box 7 will reciprocate left and right while vibrating. The vibration of the screen box 7 will accelerate the screening of the tablet core particles, thereby realizing efficient screening work, and the reciprocating left and right movement of the screen box 7 can effectively avoid the problem of reduced screening efficiency due to material accumulation. In this way, the influence of large-sized particles on the sieve holes is reduced, and the phenomenon of sieve hole blockage is effectively reduced, which is conducive to improving the screening efficiency of tablet core particles and subsequent production efficiency.

[0040] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims

1. A mesalazine oral controlled-release pharmaceutical composition, comprising a core portion and a coating portion, characterized in that: The coating part is wrapped in the outer layer of the core part, and the core part is composed of mesalazine and auxiliary material components, and the auxiliary material components include matrix material, filler, adhesive and lubricant. The coating part is composed of acid-resistant material, plasticizer and light-shielding agent. The matrix material is a hydrophilic matrix material, and the ingredients contained therein include hydroxypropyl methylcellulose, sodium carboxymethyl cellulose and carbomer. The acid-resistant material can be any one of the polymers and copolymers of acrylic acid and methacrylic acid.

2. A mesalazine oral controlled-release pharmaceutical composition according to claim 1, characterized in that: The mass proportion of the mesalazine in the tablet core is 70%, the mass proportion of the matrix material in the tablet core is 20%, the mass proportion of the hydroxypropyl methylcellulose in the matrix material in the tablet core is 13%, the mass proportion of the sodium carboxymethylcellulose in the matrix material in the tablet core is 5%, the mass proportion of the carbomer in the matrix material in the tablet core is 2%, the mass proportion of the filler in the tablet core is 6%, the mass proportion of the binder in the tablet core is 3%, the mass proportion of the lubricant in the tablet core is 1%, and the mass ratio of the core portion to the coating portion is 5:1-20:

1.

3. A mesalazine oral controlled-release pharmaceutical composition according to claim 1, characterized in that: The acid-resistant material accounts for 70% of the coating part by weight, the plasticizer accounts for 25% of the coating part by weight, and the light-shielding agent accounts for 5% of the coating part by weight.

4. The mesalazine oral controlled-release pharmaceutical composition according to claim 1, characterized in that: The material of the filler is microcrystalline cellulose or lactose, the material of the binder is povidone, and the material of the lubricant is magnesium stearate.

5. The mesalazine oral controlled-release pharmaceutical composition according to claim 1, characterized in that: The material of the plasticizer is triethyl citrate or phthalate, and the material of the opacifier is titanium dioxide.

6. A method for preparing the mesalazine oral controlled-release pharmaceutical composition according to claim 1, characterized in that: The specific preparation method is as follows: S1: First, prepare the tablet core, mix mesalazine or its pharmaceutically acceptable salt or its solvate with a hydrophilic matrix material, then add an appropriate amount of a binder, a lubricant and a filler, and prepare the tablet core by a wet granulation process; S2: Then, the prepared particles are dried using a drying device, and particles that meet the requirements are screened out using a granulation device to remove particles that are too large or too small; S3: After the granules are uniformly mixed with an appropriate amount of lubricant, the granules are pressed into tablets using a rotary tablet press, and the pressed tablets are coated. A coating liquid containing an acid-resistant material is evenly sprayed on the surface of the tablet core using a coating device to form a coating layer; S4: curing the coated tablets to enhance the stability of the coating, thereby obtaining a mesalazine oral controlled-release pharmaceutical composition with a double-layer tablet structure. The preparation process of the above-mentioned oral controlled-release mesalazine pharmaceutical composition also involves a granulation device, comprising a body (1), the upper surface of the body (1) is fixedly connected to two supporting plates (2), the upper surfaces of the two supporting plates (2) are slidably connected to a moving seat (3), a connecting plate (4) is fixedly connected between adjacent side walls of the two moving seats (3), and the inner bottom surface of the body (1) is fixedly provided with a collecting box (5); A granulation mechanism, the granulation mechanism comprises a vibration screening component, a transmission component and a transversely movable screening component, the vibration screening component comprises a No. 1 fixed plate (6) fixedly connected to the side walls of two movable seats (3), a screen box (7) is arranged inside the machine body (1), and the side walls on both sides of the screen box (7) are fixedly connected to No. 2 fixed plates (8), and two springs (9) are fixedly connected between the upper surfaces of the two No. 2 fixed plates (8) and the bottom surfaces of the two No. 1 fixed plates (6), the side wall of the machine body (1) is fixedly connected to a motor (10) through a bracket, the output end of the motor (10) is fixedly connected to a rotating shaft (11), the rotating shaft (11) is rotatably connected to the inner wall of the machine body (1) through a bearing, and the side end of the rotating shaft (11) is fixedly connected to a cam (12).

7. The method for preparing a mesalazine oral controlled-release pharmaceutical composition according to claim 6, characterized in that: The transmission assembly comprises a bearing bracket (13) fixedly connected to the side wall of the body (1); a reciprocating threaded rod (14) is provided on the side of the body (1); the reciprocating threaded rod (14) is rotatably connected to the side wall of the bearing bracket (13) through a bearing; a driving wheel (15) is fixedly connected to the circumference of the rotating shaft (11); a driven wheel (16) is fixedly connected to the circumference of the reciprocating threaded rod (14); and a belt (17) is sleeved between the driving wheel (15) and the driven wheel (16).

8. The method for preparing a mesalazine oral controlled-release pharmaceutical composition according to claim 7, characterized in that: The transversely movable screening assembly includes a nut (18) threadedly connected to a reciprocating threaded rod (14), the side walls of the nut (18) are fixedly connected to force plates (19), the side walls of the two force plates (19) are fixedly connected to connecting rods (20), the side ends of the two connecting rods (20) are fixedly connected to the side walls of adjacent movable seats (3), the upper surface of the nut (18) is fixedly connected to a guide plate (21), the side walls of the guide plate (21) are fixedly connected to a guide rod (22), and the guide rod (22) penetrates and is slidably connected to the side wall of the supporting bracket (13).

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