CN111358759A - Preparation method of andrographolide enteric-coated tablets - Google Patents
Preparation method of andrographolide enteric-coated tablets Download PDFInfo
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- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
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- A61K9/2806—Coating materials
- A61K9/2833—Organic macromolecular compounds
- A61K9/286—Polysaccharides, e.g. gums; Cyclodextrin
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- A61K9/2886—Dragees; Coated pills or tablets, e.g. with film or compression coating having two or more different drug-free coatings; Tablets of the type inert core-drug layer-inactive layer
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Abstract
The invention relates to the technical field of medicines, and in particular relates to a preparation method of andrographolide enteric-coated tablets. The specific technical scheme is as follows: a method for preparing andrographolide enteric-coated tablet comprises adding adhesive, andrographolide, lactose and microcrystalline cellulose into a high-speed mixing wet granulation device, mixing, and granulating; then adding the prepared medicine particles into a boiling dryer for drying, wherein the water content is controlled to be 2-5%; granulating the dried drug granules by using a granulator, and finally tabletting by using a high-speed rotary tabletting machine to obtain andrographolide enteric-coated tablet cores; and coating the enteric-coated tablet core with an isolating layer and an enteric-coated layer. The invention solves the problem that the existing andrographolide dispersible tablets are easy to degrade in gastric juice.
Description
Technical Field
The invention relates to the technical field of medicines, and in particular relates to a preparation method of andrographolide enteric-coated tablets.
Background
Andrographolide, molecular formula C20H30O5The main effective components of natural plant andrographis paniculata have the efficacies of clearing away heat and toxic material, diminishing inflammation and relieving pain, have special curative effects on bacterial and viral upper respiratory tract infection and dysentery, and are known as natural antibiotic drugs.
The andrographolide preparations for clinical application mainly comprise andrographolide tablets, andrographolide soft capsules, andrographolide dropping pills and andrographolide dispersible tablets at present, and the preparations are gastric-dissolved preparations. The detection results of andrographolide tablets, andrographolide soft capsules, andrographolide dropping pills and andrographolide dispersible tablets under the weak acid condition show that the actual content of the effective components is only 40-50% of the labeled amount, which indicates that andrographolide is very easy to degrade in gastric juice, so that the preparation method of andrographolide enteric-coated tablets which are not easy to degrade in gastric juice needs to be provided.
Disclosure of Invention
Aiming at the defects of the prior art, the invention provides a preparation method of andrographolide enteric-coated tablets, which solves the problem that the existing andrographolide dispersible tablets are easy to degrade in gastric juice.
In order to achieve the purpose, the invention is realized by the following technical scheme:
the invention discloses a preparation method of andrographolide enteric-coated tablets, which comprises the following steps:
(1) preparation of the tablet core
Dissolving hydroxypropyl cellulose in 20-95% ethanol water solution, and adding sodium dodecyl sulfate to prepare a solution with solid content of 3-15% as an adhesive;
sieving andrographolide, lactose and microcrystalline cellulose, adding into a high-speed mixing wet granulation device, mixing, adding the prepared adhesive, and granulating; then adding the prepared medicine particles into a boiling dryer for drying, wherein the water content is controlled to be 2-5%; granulating the dried drug granules by using a granulator, and finally tabletting by using a high-speed rotary tabletting machine to obtain andrographolide enteric-coated tablet cores;
(2) wrapping and isolating layer
Preparing the raw materials of the isolating layer into a solution with the solid content of 3-15% by using pure water or 20-95% ethanol water solution, uniformly stirring, and coating by using a coating machine;
(3) coated with enteric layer
Preparing the raw materials of the enteric-coated layer and the plasticizer into enteric-coated liquid with the solid content of 3-15% by using pure water or 20-80% ethanol water solution, uniformly stirring by using an air pump stirrer, and coating by using a coating machine to obtain the andrographolide enteric-coated tablet.
Preferably, the composition comprises, by weight, 3-10 parts of andrographolide, 6-15 parts of lactose and microcrystalline cellulose in total, 0.5-2 parts of hydroxypropyl cellulose, 0.01-0.1 part of sodium dodecyl sulfate, 3-12 parts of an isolation layer, 4-30 parts of an enteric layer and 0.05-0.5 part of a plasticizer.
Preferably, the isolating layer is hydroxypropyl methylcellulose, Opadriamb II,
II. One or more of Opadry 03K19229, Opadry Y-1-7000, Opadry YS-1-7003 and Opadry Y-30-18037.
Preferably, the enteric layer is
L100-55, cellulose acetate phthalate, acrylic resin II, acrylic resin III, hydroxypropyl methyl cellulose phthalate and polyvinyl alcohol acetate phthalicA mixture of one or more of the acid esters.
Preferably, the plasticizer is one or more of triethyl citrate, dibutyl sebacate, propylene glycol and polyethylene glycol.
Preferably, in the step (2), the rotating speed of the coating machine is 2-8 rpm, the air inlet temperature is 90-110 ℃, the atomization pressure is 0.1-0.4 MPa, the pump liquid speed is 10-30 mL/min, the temperature of a tablet bed in the coating machine is controlled to be 35-45 ℃, and the weight gain of the isolation layer is controlled to be 10-40% of that of the tablet core.
Preferably, in the step (3), the rotating speed of the coating machine is 3-10 rpm, the air inlet temperature is 60-80 ℃, the atomization pressure is 0.1-0.4 MPa, the pump liquid speed is 15-40 mL/min, the temperature of a tablet bed in the coating machine is controlled to be 38-43 ℃, and the weight gain of the enteric layer is controlled to be 5-80% of the weight of the tablet core coated with the isolation layer.
Preferably, the high-speed mixing wet granulation device comprises an atomizing cylinder and a mixing cylinder which is arranged at the axis of the atomizing cylinder and is rotationally connected with the atomizing cylinder; the side wall of the mixing cylinder is provided with a plurality of atomizing mechanisms, a plurality of rows of through holes are uniformly distributed on the side wall of the mixing cylinder along the axial direction of the mixing cylinder, the axis of the mixing cylinder is provided with the mixing mechanism, and a rotatable sealing mechanism is arranged in the mixing cylinder;
sealing mechanism is including setting up the carousel of bottom in the mixing drum, the edge of carousel be provided with the through-hole is symmetrical, and with the cowl that the mixing drum inner wall was laminated mutually, the bottom is provided with the arc wall rather than the axle center is symmetrical in the mixing drum, the bottom of carousel be provided with the symmetrical lug of carousel center department, the lug with arc wall looks adaptation, carousel bottom center department is fixed with the dwang, the dwang passes the bottom of mixing drum, stretch out the bottom of an atomizing section of thick bamboo is connected with first motor.
Preferably, the bottom of an atomizing section of thick bamboo centers on the axle center department of an atomizing section of thick bamboo is provided with the ring channel, the bottom of a mixing drum be provided with the annular bulge of ring channel looks adaptation, the interior top of an atomizing section of thick bamboo with be provided with round L type spout on the symmetrical position of ring channel, open-top and top circumference of a mixing drum be provided with the round with the flange of L type spout looks adaptation, make the mixing drum passes through the cooperation of L type spout and flange and the protruding cooperation of ring channel and ring and is in the atomizing section of thick bamboo internal rotation.
Preferably, the atomizing mechanism comprises a plurality of atomizing pipes, one ends of the atomizing pipes extend into the atomizing cylinder, the other ends of the atomizing pipes are respectively connected to the side wall of the main pipeline, and the other end of the main pipeline is connected with the stirring mechanism; the end part of the atomizing pipe extending into the atomizing cylinder is provided with a spray head, the caliber of the upper nozzle of the spray head is gradually reduced from the inside of the spray head to the outside of the spray head, and the inner diameter of the atomizing pipe is gradually reduced from the spray head.
The invention has the following beneficial effects:
1. according to the invention, the high-speed mixing wet granulation device is adopted, the quality of the prepared tablet core is stable and has no loss, and in order to prevent the reaction of the tablet core and the enteric coating, the tablet core is isolated by the isolation layer, so that the quality of the tablet core is effectively protected; meanwhile, the weight increment of the isolation layer and the enteric-coated layer is controlled, so that the enteric-coated tablet can be kept complete within 2 hours at low pH (gastric acid) and can be quickly dissolved out and release the medicine within 15 minutes at higher pH (artificial intestinal juice), and the quality and the curative effect of the product are ensured. The tablet prepared by the invention is easy to carry, convenient to take, simple in production process and easy to operate and industrially produce.
2. The invention mixes andrographolide and pharmaceutically acceptable auxiliary materials to prepare tablets, then coats the tablets with an isolating coat to avoid the influence of andrographolide on acidic substances (such as enteric coating materials), and then coats with an enteric coating to ensure that the andrographolide is not released or almost not released in a specified acidic medium (gastric acid) and is mostly or completely released in phosphate buffer solution (artificial intestinal juice) with the pH value of 6.8 within a required time. The andrographolide is different in solubility in different pH media, namely, the andrographolide is kept complete in low pH (gastric acid) and is dissolved out and released in high pH (artificial intestinal juice), so that the medicine is released in intestines after being orally taken, the damage of gastric acid is avoided, the medicine can be quickly dissolved and released after successfully reaching the intestinal tract, the problem of bioavailability of andrographolide in oral administration is effectively improved, and the curative effect of the medicine is guaranteed.
3. The invention can complete the mixing of the medicine and the wet granulation by a high-speed mixing wet granulation device, and specifically comprises the following steps: the bottom of the mixing cylinder is provided with a rotary disc, a plurality of arc-shaped baffles are uniformly distributed on the edge of the rotary disc and used for blocking through holes formed in the side wall of the mixing cylinder, when a mixing mechanism uniformly mixes raw materials added into the mixing cylinder, a first motor is started again, the rotary disc rotates for a certain angle, the arc-shaped baffles are moved to a position between two rows of through holes, so that the through holes are leaked out, in the process of continuing operation of the first motor, a lug at the bottom of the rotary disc enables the mixing cylinder to rotate in an annular groove through an annular bulge at the bottom of the mixing cylinder, and finally, in the process of centrifugal force generated by rotation of the mixing cylinder, mixed raw material powder is sprayed out through the through holes; meanwhile, the pressure pump sprays the adhesive in the mixing drum in a foggy shape from the spray head, the adhesive is combined with the medicine powder sprayed from the through hole in the air, and the stirring paddle and the stirring blade which are arranged on the side wall of the mixing drum increase the contact time of the adhesive and the raw material powder, so that the raw material powder is prevented from falling to the bottom of the atomizing drum without being contacted with the adhesive to the greatest extent, the waste of the raw material powder is caused, and the effective components in the finally prepared enteric-coated tablet are not up to the standard.
Drawings
FIG. 1 is a schematic structural view of the present invention;
FIG. 2 is an enlarged view of a portion A of FIG. 1;
FIG. 3 is an enlarged view of a portion B of FIG. 1;
FIG. 4 is a schematic view of a connecting structure of a mixing drum and a stirring blade;
FIG. 5 is a schematic structural view of another embodiment of a stirring paddle;
FIG. 6 is a view taken along line A-A of FIG. 1;
FIG. 7 is a schematic view of a connecting structure of the mixing drum and the sealing mechanism;
FIG. 8 is a view taken along line B-B of FIG. 7;
FIG. 9 is a schematic view of a connection structure of the L-shaped chute and the mixing drum;
FIG. 10 is a schematic view of the discharge mechanism open;
in the figure: atomizing cylinder 1, mixing drum 2, through-hole 3, carousel 4, cowl 5, arc 6, lug 7, dwang 8, first motor 9, annular arch 10, L type spout 11, atomizing pipe 12, main pipe 13, shower nozzle 14, churn 15, (mixing) shaft 16, stirring vane 17, second motor 18, force pump 19, mixing shaft 20, helical blade 21, third motor 22, stirring rake 23, stirring vane 24, connecting rod 25, fixed column 26, quad slit 27, discharge gate 28, play feed cylinder 29, discharging pipe 30, cylinder 31, sealing block 32.
Detailed Description
The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the drawings in the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
Unless otherwise indicated, the technical means used in the examples are conventional means well known to those skilled in the art.
The invention discloses a preparation method of andrographolide enteric-coated tablets, which specifically comprises the following steps:
(1) preparation of the tablet core
Dissolving hydroxypropyl cellulose in 20-95% ethanol water solution, and adding sodium dodecyl sulfate to prepare a solution with solid content of 3-15% as an adhesive;
sieving andrographolide, lactose and microcrystalline cellulose, adding into a high-speed mixing wet granulation device, mixing, adding the prepared adhesive, and granulating; then adding the prepared medicine particles into a boiling dryer for drying, wherein the water content is controlled to be 2-5%; granulating the dried drug granules by using a granulator, and finally tabletting by using a high-speed rotary tabletting machine to obtain andrographolide enteric-coated tablet cores; the mesh number of sieving the andrographolide, the lactose and the microcrystalline cellulose is selected according to the actual situation.
(2) Wrapping and isolating layer
Preparing the raw materials of the isolating layer into a solution with the solid content of 3-15% by using pure water or 20-95% ethanol water solution (mass percentage), uniformly stirring, and coating by using a coating machine; the coating machine rotates for 20min at the rotating speed of 2-8 rpm, the air inlet temperature is 90-110 ℃, the atomization pressure is 0.1-0.4 MPa, the liquid pumping speed is 10-30 mL/min, the temperature of a tablet bed in the coating machine is controlled to be 35-45 ℃, and the weight gain of an isolation layer is controlled to be 10-40% of that of the tablet core.
(3) Coated with enteric layer
Preparing raw materials of an enteric layer and a plasticizer into enteric coating liquid with the solid content of 3-15% by using pure water or 20-80% ethanol water solution (in percentage by mass), uniformly stirring by using an air pump stirrer, and then coating by using a coating machine, wherein the rotating speed of the coating machine is 3-10 rpm, the coating machine rotates for 20min, the air inlet temperature is 60-80 ℃, the atomization pressure is 0.1-0.4 MPa, the pump liquid speed is 15-40 mL/min, the tablet bed temperature in the coating machine is controlled to be 38-43 ℃, and the weight gain of the enteric layer is controlled to be 5-80% of the weight of an isolation layer coated on a tablet core; finally, the andrographolide enteric-coated tablet is obtained.
According to parts by weight, 3-10 parts of andrographolide, 6-15 parts of lactose and microcrystalline cellulose in total, 0.5-2 parts of hydroxypropyl cellulose, 0.01-0.1 part of sodium dodecyl sulfate, 3-12 parts of an isolating layer, 4-30 parts of an enteric layer and 0.05-0.5 part of a plasticizer.
The isolating layer is hydroxypropyl methylcellulose, Opadriamb II,
II. One or more of Opadry 03K19229, Opadry Y-1-7000, Opadry YS-1-7003 and Opadry Y-30-18037.
The enteric layer is
L100-55, cellulose acetate phthalate, acrylic resin II, acrylic resin III, hydroxypropyl methyl cellulose phthalate and polyvinyl alcohol acetate phthalate.
The plasticizer is one or more of triethyl citrate, dibutyl sebacate, propylene glycol and polyethylene glycol.
In the present invention, the fluidized dryer, the granulator, the high-speed rotary tablet press and the coating machine are conventional apparatuses.
In the process of preparing the tablet core, the prior art mostly adopts a high-speed mixing wet granulator to mix and granulate the mixture of the adhesive, the andrographolide, the lactose and the microcrystalline cellulose, but in the process of mixing and granulating, the prepared medicine particles are not uniform in size, and some medicine powder is not contacted with the adhesive, so that in the subsequent drying and granulating process, the powder in the medicine particles needs to be screened out in advance, and the problem exists, because the weight of each raw material is prepared in advance, if the powder is screened out, the raw material components or the effective components in the finally prepared enteric-coated tablet are different from the theoretical value, and the medicine effect of the andrographolide enteric-coated tablet is greatly reduced. Therefore, the present invention has been made in an effort to solve the above problems by newly developing a new high-speed mixing wet granulation apparatus.
Referring to fig. 1-10, the invention discloses a high-speed mixing wet granulation device, which comprises an atomizing cylinder 1 and a mixing cylinder 2 which is arranged at the axis of the atomizing cylinder 1 and is rotationally connected with the atomizing cylinder 1. The method specifically comprises the following steps: the bottom of the atomizing cylinder 1 is provided with an annular groove around the axis of the atomizing cylinder 1, the annular groove is circular, the bottom of the mixing cylinder 2 is provided with an annular protrusion 10 matched with the annular groove, namely, the annular protrusion 10 is arranged in the annular groove, and the mixing cylinder 2 rotates in the annular groove through the annular protrusion 10. In order to avoid shaking the top of the mixing drum 2, a circle of L-shaped sliding grooves 11 are formed in the positions, symmetrical (up-down symmetrical) to the annular groove, of the inner top of the atomizing drum 1, a circle of flanges matched with the L-shaped sliding grooves 11 are circumferentially arranged on the top of the top opening of the mixing drum 2, namely the bottom surfaces of the flanges are attached to the top surfaces of the transverse parts of the L-shaped sliding grooves 11, the flanges are clamped in the L-shaped sliding grooves 11, and the mixing drum 2 rotates in the L-shaped sliding grooves 11. Finally, the mixing cylinder 2 rotates in the atomizing cylinder 1 through the matching of the L-shaped sliding groove 11 and the rib and the matching of the annular groove and the annular bulge 10.
The side wall of the mixing cylinder 2 is provided with a plurality of atomizing mechanisms for spraying the adhesive into the atomizing cylinder 1. Atomizing mechanism includes that a plurality of one end stretches into atomizing pipe 12 in the atomizing barrel 1, and atomizing pipe 12 sets up on the lateral wall of atomizing barrel 1 unordered, and on the other end of all atomizing pipes 12 was connected to the lateral wall of trunk line 13 respectively jointly, and the other end of trunk line 13 was connected with rabbling mechanism. The stirring mechanism comprises a stirring drum 15, a stirring shaft 16 vertically arranged in the stirring drum 15 and a stirring blade 17 arranged on the stirring shaft 16, wherein the stirring drum 15 is arranged at the top of the atomizing drum 1, a charging opening is formed in the top of the stirring drum 15, one end of the stirring shaft 16 extends out of the top of the stirring drum 15 and is connected with a second motor 18, the bottom of the stirring drum 15 is connected with a main pipeline 13, and a valve and a pressure pump 19 are sequentially arranged on the main pipeline 13 from top to bottom. It should be noted that: if there are more atomizing pipes 12 disposed on the side wall of the atomizing barrel 1, a plurality of stirring mechanisms may be disposed on the top of the atomizing barrel 1, the stirring mechanisms are used for preparing the adhesive, and the adhesive is sprayed into the atomizing barrel 1 by the pressure pump 19, and preferably 2 stirring mechanisms are disposed in the present invention. In order to atomize the adhesive sprayed into the atomizing cylinder 1 as much as possible, a spray head 14 is arranged at the end of an atomizing pipe 12 extending into the atomizing cylinder 1, the caliber of the upper spray opening of the spray head 14 is gradually reduced from the inside of the spray head 14 to the outside of the spray head 14, the inner diameter of the atomizing pipe 12 is gradually reduced toward the spray head 14, so that the pressure of the adhesive sprayed into the atomizing cylinder 1 is increased, and the adhesive is sprayed in a mist form.
A plurality of rows of through holes 3 are uniformly distributed on the side wall of the mixing cylinder 2 along the axial direction of the mixing cylinder 2, and the size of the through holes 3 is set according to actual needs. The invention preferably arranges 6 rows of through holes 3 which are equidistantly arranged on the side wall of the mixing cylinder 2, the axle center of the mixing cylinder 2 is provided with a mixing mechanism, the mixing mechanism comprises a mixing shaft 20 arranged at the axle center of the mixing cylinder 2 and a helical blade 21 arranged on the mixing shaft 20, one end of the mixing shaft 20 extends out of the mixing cylinder 2 and out of the top of the atomizing cylinder 1, one end of the mixing shaft 20 extending out of the top of the atomizing cylinder 1 is connected with a third motor 22, the mixing shaft 20 is connected with the atomizing cylinder 1 through a sealing bearing, namely, the mixing shaft 20 is fixed on the inner ring of the sealing bearing, and the outer ring of the sealing bearing is fixed on the atomizing cylinder 1. The third motor 22 is fixed on the top of the atomizing cylinder 1 through a bracket, and the other end of the mixing shaft 20 is separated from the rotating disc 4. And, be provided with the material loading mouth at the top of atomizing section of thick bamboo 1, position and the top of mixing drum 2, can connect with the hose on the material loading mouth, feed in mixing drum 2 through the hose, also can feed in mixing drum 2 at any time.
In order to mix and granulate the raw materials in the mixing cylinder 2 by spraying the raw materials from the through holes 3 and the adhesive sprayed from the spray head 14, a rotatable sealing mechanism is arranged in the mixing cylinder 2, and in the process of mixing the raw materials, the sealing mechanism blocks all the through holes 3, and the through holes 3 are opened again until the raw materials are mixed. Specifically, the method comprises the following steps: the sealing mechanism comprises a rotary disc 4 arranged at the bottom in the mixing drum 2, and the rotary disc 4 is matched with the bottom of the mixing drum 2, so that the rotary disc 4 can be just placed in the mixing drum 2. Arc-shaped baffles 5 which are symmetrical to the through holes 3 and are attached to the inner wall of the mixing drum 2 are arranged around the edge of the rotary table 4, namely the arc-shaped baffles 5 are strip-shaped and can block each row of the through holes 3, so that the through holes 3 are completely blocked; and the convex arc part of the arc baffle 5 is attached to the inner wall of the mixing cylinder 2.
In order to make the powder be ejected from the through-holes 3 after the mixing of the raw materials is completed, the arc-shaped baffle 5 needs to be removed from the through-holes 3. The method specifically comprises the following steps: the bottom is provided with the arc wall 6 rather than the axle center symmetry in mixing drum 2, and the bottom of carousel 4 is provided with the lug 7 with 4 center departments of carousel symmetry, lug 7 and 6 looks adaptations of arc wall, and 4 bottom centers of carousel are fixed with dwang 8, and dwang 8 passes the bottom of mixing drum 2, stretches out the bottom of atomizing section of thick bamboo 1 and is connected with first motor 9. It should be understood that: because the through holes 3 have 6 rows, the radian of the arc-shaped baffle 5 is preferably 15-60 degrees, and the radian of the arc-shaped groove 6 is preferably 60 degrees. In the present invention, when the arc-shaped baffle 5 blocks the through hole 3, the two protrusions 7 are both positioned at the left side of the arc-shaped groove 6, as shown in fig. 8. The dwang 8 is fixed with mixing drum 2 and atomizing drum 1 through sealed bearing respectively, and is same, and dwang 8 is fixed with sealed bearing's inner circle, and sealed bearing's outer lane is fixed with mixing drum 2 and atomizing drum 1. The specific operation process is as follows: after mixing mechanism is with raw materials misce bene, start first motor 9 clockwise rotation 60, make carousel 4 also rotatory 60 in arc wall 6 through lug 7 of its bottom, thereby make cowl 5 also remove 60, spill through-hole 3, first motor 9 continues to keep clockwise rotation this moment, because lug 7 can't continue to rotate in arc wall 6, continue to make lug 7 drive mixing drum 2 pass through the protruding 10 of annular of its bottom at the ring channel internal rotation, reach mixing drum 2 and rotate the raw materials powder that makes in the mixing drum 2 and spout from through-hole 3 through centrifugal force, mixing mechanism continues to keep the operation this moment, make the blowout of every through-hole 3 of follow that raw materials powder can be even. Meanwhile, the pressure pump 19 sprays the adhesive in the mixing drum 15 through the spray head 14, so that the adhesive and the raw material powder are mixed and granulated in the cavity between the mixing drum 2 and the atomizing drum 1, at the moment, the stirring paddle 23 and the stirring blade 24 stir the adhesive, the raw material powder and the prepared medicine particles, the contact probability of the adhesive and the raw material powder is increased, the larger medicine particles are crushed, the prepared medicine particles are uniform, and the raw material powder in the medicine particles is reduced as much as possible. When the through hole 3 needs to be blocked again, the arc-shaped baffle 5 can be blocked by controlling the first motor 9 to rotate 60 degrees anticlockwise. And after the granulation is finished, starting the discharging mechanism to finish discharging.
Further, in order to make the drug particles formed by mixing the binder and the mixed raw material powder uniform, a stirring paddle 23 is fixed on the outer wall of the mixing cylinder 2 near the bottom thereof, and inclined cutting edges are provided on both sides of the stirring paddle 23 in the length direction, or an inclined surface (see fig. 5) with one side high and one side low is provided, so that the drug particles or the falling powder at the bottom of the atomizing cylinder 1 are stirred to perform better mixing granulation. The invention preferably fixes 3 stirring paddles 23 at equal intervals and on the same level, and a plurality of stirring blades 24 are arranged above the stirring paddles 23 and on the side wall of the mixing cylinder 2 in disorder and in a detachable way, and the stirring blades 24 can well mix and granulate the atomized adhesive and the sprayed powder. The method specifically comprises the following steps: on the lateral wall of mixing drum 2, set up longitudinal symmetry on the position that does not have through-hole 3, and through the fixed column 26 of connecting rod 25, and offer the quad slit 27 that supplies fixed column 26 to pass at the one end of stirring leaf 24, stirring leaf 24 is worn into the fixed column 26 that is located the below through quad slit 27 promptly, and connecting rod 25 is then fixed in the one end of keeping away from the mixing drum 2 lateral wall, makes connecting rod 25 restrict stirring leaf 24 on fixed column 26, and makes stirring leaf 24 can move about on connecting rod 25 and fixed column 26. Of course, the connecting rod 25 may be a bolt, and threaded holes are provided on the two fixing posts 26, so that the stirring blade 24 can be removed when the stirring blade 24 is not needed.
Furthermore, a discharging mechanism is arranged on the side wall of the atomizing barrel 1 and near the bottom of the atomizing barrel, a discharging hole 28 is arranged on the side wall of the atomizing barrel 1, the discharging mechanism is arranged on the discharging hole 28, the discharging mechanism comprises a discharging barrel 29 and a discharging pipe 30 which is arranged at the bottom of the discharging barrel 29 and communicated with the discharging barrel, and the diameter of the discharging barrel 29 is larger than the aperture of the discharging hole 28. There is cylinder 31 at the end fixing of play feed cylinder 29, the tip that the output of cylinder 31 passes through play feed cylinder 29 stretches into in the feed cylinder 29, and its end fixing has sealed piece 32, sealed piece 32 is preferably echelonment, its minor diameter end and discharge gate 28 looks adaptation, make the minor diameter end of sealed piece 32 just to plug up discharge gate 28, and the terminal surface of the big diameter end of sealed piece 32 and the minor diameter end junction is laminated with the outer wall of the atomizing barrel 1 between discharge gate 28 and the play feed cylinder 29 inner wall mutually, make sealed piece 32 can be fine seal discharge gate 28, and the control discharge gate 28 that can be fine opens and close through cylinder 31.
After the wet granulation is finished by using the high-speed mixing wet granulation device, the prepared medicine granules almost have no medicine powder, and the powder in the medicine granules can be directly added into a boiling dryer for direct drying without filtering.
Examples
The specific component ratio of the andrographolide enteric-coated tablets prepared by the method is shown in the following table 1.
TABLE 1 raw material ratio (parts by weight)
The tablet cores were prepared according to the ratios in table 1, the parameters during the operation of the high-speed mixing wet granulation apparatus are shown in table 2 below, and the ratios in table 1 were prepared using the parameters set in table 2 below.
Table 2 specific Process parameters
After the tablet core is prepared, the tablet core is coated with an isolating layer and an enteric layer, and the technological parameters of the coating machine in the process of coating the isolating layer and the enteric layer are shown in the following table 3.
TABLE 3 coating machine Process parameters
Granulating each group of raw materials in the table 1 by using the parameters in the table 2 and a high-speed mixing wet granulation device, drying, granulating and tabletting, respectively coating an isolation layer and an enteric layer by using the process parameters in the table 3, and finally preparing the andrographolide enteric-coated tablet.
Comparative example
During mixing and granulating, the existing high-speed mixing wet granulator is used for granulating, and the rest steps, the raw material ratio and the process parameters are the same as those of the embodiment.
The andrographolide enteric-coated tablets, andrographolide common tablets (without an isolating layer and an enteric-coated layer) prepared by the method and enteric-coated tablet prepared in proportion are respectively placed in hydrochloric acid solution with the pH value of 1.5 for 2 hours, then placed in phosphate buffer solution with the pH value of 6.8 for 45min, and sampled and measured in 30min, 60min, 90min, 120min, 135min, 145min, 155min and 165min time periods respectively to determine the cumulative release rate, and the average result is shown in the following table 4.
TABLE 4 cumulative release results for enteric coated tablets
In the description of the present invention, it is to be understood that the terms "longitudinal", "lateral", "upper", "lower", "front", "rear", "left", "right", "vertical", "horizontal", "top", "bottom", "inner", "outer", and the like, indicate orientations or positional relationships based on those shown in the drawings, are merely for convenience of description of the present invention, and do not indicate or imply that the referenced devices or elements must have a particular orientation, be constructed and operated in a particular orientation, and thus, are not to be construed as limiting the present invention.
The above-described embodiments are merely illustrative of the preferred embodiments of the present invention, and do not limit the scope of the present invention, and various modifications and improvements of the technical solutions of the present invention can be made by those skilled in the art without departing from the spirit of the present invention, and the technical solutions of the present invention are within the scope of the present invention defined by the claims.
Claims (10)
1. A preparation method of andrographolide enteric-coated tablets is characterized by comprising the following steps: the method comprises the following steps:
(1) preparation of the tablet core
Dissolving hydroxypropyl cellulose in 20-95% ethanol water solution, and adding sodium dodecyl sulfate to prepare a solution with solid content of 3-15% as an adhesive;
sieving andrographolide, lactose and microcrystalline cellulose, adding into a high-speed mixing wet granulation device, mixing, adding the prepared adhesive, and granulating; then adding the prepared medicine particles into a boiling dryer for drying, wherein the water content is controlled to be 2-5%; granulating the dried drug granules by using a granulator, and finally tabletting by using a high-speed rotary tabletting machine to obtain andrographolide enteric-coated tablet cores;
(2) wrapping and isolating layer
Preparing the raw materials of the isolating layer into a solution with the solid content of 3-15% by using pure water or 20-95% ethanol water solution, uniformly stirring, and coating by using a coating machine;
(3) coated with enteric layer
Preparing the raw materials of the enteric-coated layer and the plasticizer into enteric-coated liquid with the solid content of 3-15% by using pure water or 20-80% ethanol water solution, uniformly stirring by using an air pump stirrer, and coating by using a coating machine to obtain the andrographolide enteric-coated tablet.
2. The method for preparing andrographolide enteric-coated tablets according to claim 1, wherein the steps of: according to parts by weight, 3-10 parts of andrographolide, 6-15 parts of lactose and microcrystalline cellulose in total, 0.5-2 parts of hydroxypropyl cellulose, 0.01-0.1 part of sodium dodecyl sulfate, 3-12 parts of an isolating layer, 4-30 parts of an enteric layer and 0.05-0.5 part of a plasticizer.
3. The method for preparing andrographolide enteric-coated tablets according to claim 2, wherein the steps of: the isolating layer is hydroxypropyl methylcellulose, Opadry ambII,
II. One or more of Opadry 03K19229, Opadry Y-1-7000, Opadry YS-1-7003 and Opadry Y-30-18037.
4. The method for preparing andrographolide enteric-coated tablets according to claim 2, wherein the steps of: the enteric layer is
L100-55, cellulose acetate phthalate, acrylic resin II, acrylic resin III, hydroxypropyl methyl cellulose phthalate and polyvinyl alcohol acetate phthalate.
5. The method for preparing andrographolide enteric-coated tablets according to claim 2, wherein the steps of: the plasticizer is one or a mixture of triethyl citrate, dibutyl sebacate, propylene glycol and polyethylene glycol.
6. The method for preparing andrographolide enteric-coated tablets according to claim 1, wherein the steps of: in the step (2), the rotating speed of the coating machine is 2-8 rpm, the air inlet temperature is 90-110 ℃, the atomization pressure is 0.1-0.4 MPa, the liquid pumping speed is 10-30 mL/min, the temperature of a tablet bed in the coating machine is controlled to be 35-45 ℃, and the weight gain of an isolation layer is controlled to be 10-40% of that of the tablet core.
7. The method for preparing andrographolide enteric-coated tablets according to claim 1, wherein the steps of: in the step (3), the rotating speed of the coating machine is 3-10 rpm, the air inlet temperature is 60-80 ℃, the atomization pressure is 0.1-0.4 MPa, the pumping speed is 15-40 mL/min, the temperature of a tablet bed in the coating machine is controlled to be 38-43 ℃, and the weight gain of an enteric layer is controlled to be 5-80% of the weight of the tablet core coated with an isolation layer.
8. The method for preparing andrographolide enteric-coated tablets according to claim 1, wherein the steps of: the high-speed mixing wet granulation device comprises an atomizing cylinder (1) and a mixing cylinder (2) which is arranged at the axis of the atomizing cylinder (1) and is rotationally connected with the atomizing cylinder (1); the side wall of the mixing cylinder (2) is provided with a plurality of atomizing mechanisms, a plurality of rows of through holes (3) are uniformly distributed on the side wall of the mixing cylinder (2) along the axial direction of the mixing cylinder (2), the mixing mechanism is arranged at the axis of the mixing cylinder (2), and a rotatable sealing mechanism is arranged in the mixing cylinder (2);
sealing mechanism is including setting up carousel (4) of bottom in mixing drum (2), the edge of carousel (4) be provided with through-hole (3) symmetry, and with cowl (5) that mixing drum (2) inner wall laminated mutually, the bottom is provided with rather than symmetrical arc wall (6) in axle center in mixing drum (2), the bottom of carousel (4) be provided with symmetrical lug (7) are located at carousel (4) center, lug (7) with arc wall (6) looks adaptation, carousel (4) bottom center department is fixed with dwang (8), dwang (8) pass the bottom of mixing drum (2), stretch out the bottom of an atomizing section of thick bamboo (1) is connected with first motor (9).
9. The method for preparing andrographolide enteric-coated tablets according to claim 8, wherein the steps of: the bottom of an atomizing barrel (1) centers on the axle center department of an atomizing barrel (1) is provided with the ring channel, the bottom of a mixing drum (2) be provided with annular groove phase adaptation's annular is protruding (10), the interior top of an atomizing barrel (1) with be provided with round L type spout (11) on the symmetrical position of ring channel, the open-top of a mixing drum (2) and top circumference be provided with the round with the flange of L type spout (11) phase adaptation make mixing drum (2) are in through the cooperation of L type spout (11) and flange and the cooperation of ring channel and annular protrusion (10) atomizing barrel (1) internal rotation.
10. The method for preparing andrographolide enteric-coated tablets according to claim 8, wherein the steps of: the atomizing mechanism comprises a plurality of atomizing pipes (12) with one ends extending into the atomizing cylinder (1), the other ends of the atomizing pipes are respectively connected to the side wall of the main pipe (13), and the other end of the main pipe (13) is connected with a stirring mechanism; stretch into in the atomizing cylinder (1) the tip of atomizing pipe (12) is provided with shower nozzle (14), the bore of spout on shower nozzle (14) by the inside of shower nozzle (14) is outside shower nozzle (14) reduces gradually, the internal diameter of atomizing pipe (12) towards shower nozzle (14) reduces gradually.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2022032804A1 (en) * | 2020-08-11 | 2022-02-17 | 河北科星药业有限公司 | Compound amino acid enteric-coated tablet for dogs and preparation method therefor |
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