Production device and production method of metronidazole vaginal effervescent tablets

Abstract

The invention relates to a production device and a production method, in particular to a production device and a production method of metronidazole vaginal effervescent tablets. The metronidazole vaginal effervescent tablet prepared by the production device and the production method can be rapidly disintegrated through matching of anhydrous citric acid, carboxymethyl starch sodium and sodium bicarbonate, on one hand, metronidazole can be rapidly released through rapid disintegration, the metronidazole vaginal effervescent tablet can rapidly act on a focus to digest inflammation, on the other hand, the metronidazole vaginal effervescent tablet can be rapidly dissolved into a solution through rapid disintegration, and the metronidazole vaginal effervescent tablet can be rapidly disintegrated. And foreign body sensation can be quickly eliminated. The tablets can be isolated from air through aluminum foil packaging, and the tablets are prevented from absorbing moisture. The problems that an existing effervescent tablet takes effect slowly and has foreign body sensation for a long time due to the fact that the existing effervescent tablet has a coating layer are solved.

Description

Technical Field

[0001] The present invention relates to a production device and a production method, and particularly to a production device and a production method for metronidazole vaginal effervescent tablets. Background Art

[0002] Metronidazole vaginal effervescent tablets are tablet preparations for treating vaginitis, having the functions of sterilization, anti - inflammation and pain relief. The patent application with publication number CN104666273A discloses a metronidazole vaginal effervescent tablet and its preparation process, which consists of a metronidazole tablet core containing acidic components and an alkaline coating layer wrapped on the metronidazole tablet core. Compared with the prior art, the present invention effectively separates the acidic and alkaline effervescent agents, successfully solves the stability problem of metronidazole effervescent tablets during preparation and storage; meanwhile, significantly reduces the dosage of excipients, reduces the tablet weight, and is beneficial for patients to take medicine.

[0003] The above - mentioned effervescent tablets have a coating layer. Although the coating layer can isolate the moisture absorption of the tablet core and ensure the drug effect, during its use, due to the isolation of the coating layer, it is necessary to dissolve the coating layer first to release the drug in the tablet core, resulting in slow onset; and because the coating layer needs to be dissolved first, the above - mentioned effervescent tablets have a long survival time and need a long time to dissolve during the treatment process, leading to a long - term foreign body sensation in the vagina. Therefore, it is necessary to redesign a production device and a production method for metronidazole vaginal effervescent tablets to solve the above problems. Summary of the Invention

[0004] The purpose of the present invention is to provide a production device and a production method for metronidazole vaginal effervescent tablets that can quickly dissolve and foam, quickly take effect, and effectively reduce the foreign body sensation.

[0005] The technical solution of the present invention is as follows: A production device for metronidazole vaginal effervescent tablets, comprising a crusher, a trough - shaped mixer, a multi - directional motion mixer, a hot - air circulation oven, a swing granulator, a tablet press and a packaging machine. It is characterized in that: the tablet press consists of a frame, a die holder, a pressing cylinder, a punch, a feeding auger, a hopper, a feeding cylinder and a plunger. A die holder is arranged on the frame, and die holes are longitudinally and evenly distributed on both sides of the top of the die holder; a pressing cylinder is installed above the die holder through a bracket, and the end of the piston rod of the pressing cylinder is provided with a plurality of punches corresponding to the die holes through a support plate; a feeding auger is arranged on the die holder outside the die holes, one end of the feeding auger on the die holder is provided with a hopper, and the hopper is communicated with the feeding auger; a plurality of feeding holes are arranged at the bottom of the feeding auger corresponding to the die holes, a plunger hole is arranged at the bottom of the feeding hole, and the plunger hole and the feeding hole are arranged in an inverted T - shape and communicated with the die hole; feeding cylinders are respectively arranged on the frames on both sides of the die holder, and the end of the piston rod of the feeding cylinder is evenly provided with plungers through a cross beam, and the plungers are inserted and connected with the plunger holes.

[0006] The inner end face of the plunger is arc-shaped.

[0007] On the frame at the bottom of the die holder, a discharge cylinder is installed through a bracket. At the end of the piston rod of the discharge cylinder, multiple support rods are correspondingly installed through a support plate in relation to the die holes. The top ends of the support rods extend into the die holes, and at the end of the support rods extending into the die holes, a pressure-bearing piston is provided. The pressure-bearing piston is slidably and sealingly connected to the die holes.

[0008] A retaining flange is provided on the die hole below the pressure-bearing piston.

[0009] The height (thickness) of the pressure-bearing piston is greater than or equal to the diameter of the plunger hole.

[0010] Transverse sliding grooves are longitudinally and evenly distributed on the top end face of the die holder, and the transverse sliding grooves are respectively communicated with the die holes on both sides of the die holder.

[0011] On the frame on one side of the die holder, a pushing cylinder is provided. At the end of the piston rod of the pushing cylinder, push plates are evenly installed through a cross beam, and the push plates are inserted and connected with the transverse sliding grooves; on the other side of the die holder, a discharge conveyor belt is provided.

[0012] A male mold is provided on the bottom end face of the pressure head.

[0013] The male mold is a cross mold.

[0014] The male mold is a character mold.

[0015] A production method of metronidazole vaginal effervescent tablets is characterized in that it includes the following steps: 1) Crushing of raw and auxiliary materials Crush anhydrous citric acid through the crusher of this metronidazole vaginal effervescent tablet production device, and pass through an 80-mesh sieve to crush it into fine powder for standby; 2) Drying of raw and auxiliary materials Prepare materials according to the production prescription amount by weighing 2 - 5% more of the material amount after drying the moisture of the raw and auxiliary materials; pass sodium bicarbonate and sodium lauryl sulfate through a hot air circulation oven respectively, set the drying temperature at 50 °C, dry for 5 hours, and seal for standby; Pass anhydrous citric acid, metronidazole, lactose, sodium carboxymethyl starch, and hypromellose through a hot air circulation oven respectively, set the drying temperature at 70 °C, dry for 5 hours, and seal for standby; 3) Weighing Weigh one-third of the production prescription amount of raw and auxiliary materials per pot, weigh anhydrous citric acid, metronidazole, lactose, sodium carboxymethyl starch, hypromellose, sodium bicarbonate, and sodium lauryl sulfate, and also weigh polyvinylpyrrolidone K30 for standby; 4) Granulation Dissolve the weighed polyvinylpyrrolidone K30 in absolute ethanol to prepare a 6% polyvinylpyrrolidone K30 absolute ethanol solution; Add the weighed raw and auxiliary materials into the trough mixer by pot, stir for 40 minutes, then add 6% povidone K30 anhydrous ethanol solution, and mix for 15 minutes to make soft materials; make granules through a 30-mesh sieve in a rocking granulator, spread the granules on a baking tray, and set the drying temperature at 50 °C in a hot air circulation oven for 1.5 hours. After cooling, perform granulation. The dried and cooled granules are granulated in a rocking granulator, and the granulation screen is 30 meshes. After granulation, set the drying temperature at 50 °C in a hot air circulation oven and dry for 2 hours. 5) Total mixing Put the granules obtained after granulation into a multi-directional motion mixer, add magnesium stearate, and mix in the multi-directional motion mixer for 20 minutes to make them evenly mixed for standby. 6) Tabletting After adjusting the parameters of the tabletting machine, tablet the granules obtained from total mixing through the tabletting machine. 7) Packaging The packaging machine wraps and packs the tablets with aluminum foil.

[0016] The raw material ratio (weight ratio) of the production prescription in step 3) is as follows: anhydrous citric acid: metronidazole: lactose: sodium carboxymethyl starch: hypromellose: sodium bicarbonate: sodium lauryl sulfate: magnesium stearate = 1:1.69:1.82:0.21:0.74:0.8:0.04:0.25.

[0017] The dosage of 6% povidone K30 anhydrous ethanol solution in step 4) is 4.66 kg / pot.

[0018] The adjusted parameters in step 6) include tablet weight, tabletting pressure and tablet thickness. The tablet weight is 0.737 - 0.813 g, the tabletting pressure is 30 - 40 KN, and the tablet thickness is 4.0 - 4.1 mm.

[0019] Anhydrous citric acid is used as an acidulant, pH regulator, antioxidant, and preservative. In pharmaceuticals, it is used to adjust the pH value of drugs, improve the stability and solubility of drugs, and at the same time as a disintegrant component of effervescent tablets, reacting with alkaline substances to produce carbon dioxide gas, prompting the tablets to disintegrate rapidly. Anhydrous citric acid is extremely soluble in water and can dissolve quickly and completely to form a uniform solution. Metronidazole is a nitroimidazole antibiotic and the main component for resolving vaginal inflammation. Lactose is a filler that can increase the volume of the drug, improve the compressibility and fluidity of the drug, make the preparation well-shaped and easy to use. Sodium carboxymethyl starch is an excellent disintegrant with high water absorption and rapid swelling properties. It can cause the tablets to quickly break into fine particles in body fluids, thereby accelerating the dissolution and absorption of the drug. Sodium carboxymethyl starch swells in water to form a colloidal solution. Hydroxypropyl methylcellulose is used as a binder. In tablets, it can increase the adhesiveness and compressibility of granules, improve the hardness and stability of tablets, and can swell in cold water to form a viscous solution. Sodium bicarbonate is used in combination with acidic substances as an alkaline substance to prompt the rapid disintegration of tablets; it can also be used to adjust the pH value of drugs. Sodium dodecyl sulfate is a commonly used anionic surfactant with good wetting, emulsifying, and dispersing properties. As a wetting agent, emulsifying agent, and dispersing agent, it promotes the dispersion and dissolution of drugs and improves the stability of drugs; it is also used as a lubricant for tablets. Polyvinylpyrrolidone K30 is used as a pharmaceutical excipient and used as a binder for tablets, increasing the adhesiveness and compressibility of granules, making the tablets well-shaped. It is soluble in both water and organic solvents such as ethanol. Its high solubility and adjustable viscosity reduce the volume of the granulation solution. Magnesium stearate is used as a lubricant for tablets, which can prevent particles or powders from adhering to the die, reduce friction, make the tablets easy to demold, and ensure the integrity and appearance quality of the preparation.

[0020] The beneficial effects of the present invention are as follows: The tablets prepared by the production device and production method of the metronidazole vaginal effervescent tablets can disintegrate rapidly through the combination of anhydrous citric acid, sodium carboxymethyl starch, and sodium bicarbonate. On the one hand, rapid disintegration can quickly release metronidazole and act on the lesion to resolve inflammation rapidly. On the other hand, rapid disintegration can quickly dissolve the tablets into a solution and quickly eliminate the foreign body sensation. Encapsulation with aluminum foil can isolate the tablets from air and prevent the tablets from absorbing moisture. It solves the problems of slow onset and long-term foreign body sensation existing in existing effervescent tablets due to the presence of a coating layer. Description of the Drawings

[0021] Figure 1 is a schematic structural diagram of the tablet press of the present invention; Figure 2 is Figure 1 the schematic structural diagram in the A-A direction of Figure 3 is a schematic cross-sectional view of the die holder of the present invention; Figure 4 is Figure 2Enlarged schematic view at position B in the [specific context]; Figure 5 It is a top view schematic of the die base of the present invention; Figure 6 It is a distribution schematic of the plungers of the present invention; Figure 7 It is a distribution schematic of the push plates of the present invention; Figure 8 It is a structural schematic of the cross die of the present invention; Figure 9 It is a structural schematic of the character die of the present invention.

[0022] In the figure: 1, frame; 2, die base; 3, pressing cylinder; 4, press head; 5, feeding auger; 6, storage bin; 7, feeding cylinder; 8, plunger; 9, die hole; 10, feeding hole; 11, plunger hole; 12, discharging cylinder; 13, support rod; 14, bearing piston; 15, anti-retreat flange; 16, transverse chute; 17, pushing cylinder; 18, push plate; 19, discharging conveyor belt; 20, male die. Specific implementation method

[0023] The production method of this metronidazole vaginal effervescent tablet includes the following steps: Crush anhydrous citric acid with the crusher of the production device for this metronidazole vaginal effervescent tablet, sieve it through an 80-mesh sieve to crush it into fine powder, pack it with a clean film bag, and seal it for standby.

[0024] The production device for this metronidazole vaginal effervescent tablet includes a crusher, a trough mixer, a multi-directional motion mixer, a hot air circulation oven, a rocking granulator, a tablet press, and a packaging machine. Among them, the crusher, trough mixer, multi-directional motion mixer, hot air circulation oven, rocking granulator, and packaging machine are existing devices on the market respectively. The model of the crusher is the 20B type universal crusher; the model of the trough mixer is the CH-150L type; the model of the multi-directional motion mixer is the HD-400 type; the model of the hot air circulation oven is the pTCT-C type; the model of the rocking granulator is the YK-160 type; the model of the packaging machine is the DPP-260K2 type double-aluminum bubble packaging machine.

[0025] The tablet press is composed of a frame 1, a die holder 2, a pressing cylinder 3, a punch 4, a feeding auger 5, a hopper 6, a feeding cylinder 7 and a plunger 8. The die holder 2 is arranged on the frame 1. On both sides of the top of the die holder 2, die holes 9 are longitudinally and evenly distributed to press and form tablets in the die holes 9. The size of the die holes 9 is equal to the diameter of the tablets. Above the die holder 2, the pressing cylinder 3 is installed through a bracket. At the end of the piston rod of the pressing cylinder 3, a plurality of punches 4 are correspondingly installed through a support plate and are corresponding to the die holes 9. The function of the pressing cylinder 3 is to drive the bracket to move downward through the pressing cylinder 3, and then drive the punches 4 to move downward, so that the punches 4 are inserted into the die holes 9, and the raw materials in the die holes 9 are extruded and formed through the punches 4. On the die holder 2 outside the die holes 9, a feeding auger 5 is arranged. On the die holder 2 at one end of the feeding auger 5, a hopper 6 is arranged. The hopper 6 is communicated with the feeding auger 5 to supply materials to the feeding auger 5 through the hopper 6. Raw materials can be stored through the hopper 6, so that the feeding auger 5 can be continuously supplied with materials, and the continuous working ability of the tablet press can be maintained. At the bottom of the feeding auger 5, a plurality of feeding holes 10 are correspondingly arranged with the die holes 9. At the bottom of the feeding holes 10, a plunger hole 11 is arranged. The plunger hole 11 is arranged in an inverted T shape with the feeding hole 10 and is communicated with the die hole 9. The function of the feeding auger 5 is to feed materials to the plurality of feeding holes 10 respectively through the feeding auger 5, so that the raw materials can sequentially enter the plunger hole 11 through the feeding auger 5 and the feeding holes 10. On the frame 1 on both sides of the die holder 2, feeding cylinders 7 are respectively arranged. At the end of the piston rod of the feeding cylinder 7, a plurality of plungers 8 are evenly installed through a cross beam. The plunger 8 is inserted and connected with the plunger hole 11. The function of the feeding cylinder 7 is to push the cross beam through the feeding cylinder 7, and then push the plunger 8 to move in the plunger hole 11, so that the raw materials in the plunger hole 11 are pushed towards the die hole 9 through the moving plunger 8, thereby feeding the die hole 9, so that the raw materials can enter the die hole 9 and be pressed and formed in the die hole 9. Since the feeding auger 5 cooperates with the plunger 8 to feed multiple die holes 9 at the same time, and a plurality of punches 4 can press and form the raw materials in multiple die holes 9 at the same time, multiple tablets can be produced at one time, thereby effectively improving the pressing efficiency, greatly increasing the production capacity, and effectively meeting the production needs of enterprises. The diameters of the feeding holes 10, the plunger holes 11 and the die holes 9 can be adjusted through bushings respectively. By adjusting and controlling the diameters of the feeding holes 10 and the plunger holes 11, the feeding amount can be controlled; by adjusting and controlling the diameter of the die hole 9, the diameter and thickness of the pressed tablets can be controlled.

[0026] The inner end face of the plunger 8 is arc-shaped to seal the die hole 9 through the plunger 8, so as to avoid the raw materials entering the plunger hole 11 during the pressing process, resulting in inaccurate raw material weight; at the same time, since the inner end face of the plunger 8 is arc-shaped, the punch 4 can pass through the plunger 8, ensuring that the plunger 8 is not easily affected when closing the plunger hole 11 and the punch 4 moves downward.

[0027] On the frame 1 at the bottom of the die holder 2, a discharging cylinder 12 is installed through a bracket. At the end of the piston rod of the discharging cylinder 12, multiple support rods 13 are correspondingly installed through a support plate opposite to the die hole 9. The top ends of the support rods 13 extend into the die hole 9. At the end of the support rod 13 extending into the die hole 9, a pressure-bearing piston 14 is provided. The pressure-bearing piston 14 is slidably and sealingly connected to the die hole 9. The function of the pressure-bearing piston 14 is to extrude the raw material by cooperating with the punch 4, so as to extrude and form the raw material in the die hole 9 between the pressure-bearing piston 14 and the punch 4. The function of the discharging cylinder 12 is to drive the support rod 13 to move through the discharging cylinder 12, and then drive the pressure-bearing piston 14 to move. Thus, after extrusion molding, the moving pressure-bearing piston 14 pushes the tablet upward to push the tablet out of the die hole 9 for discharging the tablet. The pressing cylinder 3, the discharging cylinder 12 and the feeding cylinder 7 are respectively electric cylinders to accurately control the positions of the plunger 8 and the pressure-bearing piston 14 and accurately control the stroke and the downward pressure of the pressing cylinder 3.

[0028] On the die hole 9 below the pressure-bearing piston 14, a backstop flange 15 is provided to bear the pressure on the pressure-bearing piston 14 during the pressing process through the backstop flange 15.

[0029] The height (thickness) of the pressure-bearing piston 14 is greater than or equal to the diameter of the plunger hole 11, so that the pressure-bearing piston 14 can close the plunger hole 11 during the feeding process into the plunger hole 11, and the plunger 8 and the pressure-bearing piston 14 close both ends of the plunger hole 11, thereby controlling the feeding amount.

[0030] Transverse sliding grooves 16 are longitudinally and evenly distributed on the top end face of the die holder 2. The transverse sliding grooves 16 are respectively communicated with the die holes 9 on both sides of the die holder 2. On one side of the frame 1 of the die holder 2, a pushing cylinder 17 is provided. At the end of the piston rod of the pushing cylinder 17, push plates 18 are evenly installed through a cross beam. The push plates 18 are inserted and connected with the transverse sliding grooves 16; on the other side of the die holder 2, a discharging conveyor belt 19 is provided. The function of the pushing cylinder 17 is to drive the push plates 18 to move through the pushing cylinder 17, and then push the tablets to move towards the discharging conveyor belt 19 through the moving push plates 18, and push the tablets onto the discharging conveyor belt 19, thereby discharging the tablets.

[0031] On the bottom end face of the punch 4, a male mold 20 is provided. The male mold 20 is a cross mold to emboss a cross mark, so as to facilitate uniform cutting of the tablet through the cross mark. The male mold 20 is a character mold to emboss characters and emboss the company name or brand name on the tablet.

[0032] When the tablet press is working, start the discharge cylinder 12. The discharge cylinder 12 drives each pressure-bearing piston 14 to move upward through the support rod 13 to block the plunger holes 11. After the plunger holes 11 are blocked, start the feeding auger 5. The feeding auger 5 feeds the raw materials in the feed bin 6 into each feeding hole 10, and then into the plunger holes 11. After the feeding in the plunger holes 11 is completed (for a period of time), the pressure-bearing piston 14 resets to open the plunger holes 11. After the pressure-bearing piston 14 resets, start the feeding cylinder 7. The feeding cylinder 7 pushes each plunger 8, and then pushes the raw materials into the die holes 9 until the inner end face of the plunger 8 is flush with the inner wall of the die hole 9. After the injection is completed, start the pressing cylinder 3. The pressing cylinder 3 drives each punch 4 to move downward and insert into the die holes 9, and presses the raw materials into shape by the cooperation of the punch 4 and the pressure-bearing piston 14. After the tablets are formed, reset the punch 4. After the punch 4 resets, start the discharge cylinder 12. The discharge cylinder 12 drives the tablets to move upward through the support rod 13 and the pressure-bearing piston 14 in sequence, so that the tablets enter the horizontal chute 16. After the tablets are in place, start the pushing cylinder 17. The pushing cylinder 17 pushes the tablets to slide in the horizontal chute 16 through the push plate 18, and pushes the tablets onto the discharge conveyor belt 19, and transports the tablets to the next process through the discharge conveyor belt 19.

[0033] Prepare materials by weighing 2 - 5% more of the material amount after drying the moisture of the raw and auxiliary materials according to the generated prescription amount.

[0034] Spread sodium bicarbonate and sodium lauryl sulfate on the baking trays respectively, with about 2 - 3 kg loaded on each tray, and load them into the oven cart. Push the oven cart into the hot air circulation oven, set the drying temperature at 50 °C, dry for 5 hours, control the water content ≤ 0.5% (when the measurement temperature is 50 °C), (measured by a rapid moisture analyzer). After the moisture inspection is qualified, stop supplying steam. After cooling, collect in time and seal for standby.

[0035] Spread anhydrous citric acid, metronidazole, lactose, sodium carboxymethyl starch, and hypromellose on the baking trays respectively, with about 2 - 3 kg loaded on each tray, and load them into the oven cart. Push the oven cart into the hot air circulation oven, set the drying temperature at 70 °C, dry for 5 hours, control the water content ≤ 1.0% (when the measurement temperature is 70 °C), (measured by a rapid moisture analyzer). After the moisture inspection is qualified, stop supplying steam. After cooling, collect in time and seal for standby.

[0036] After calibrating the weighing instruments, weigh one-third of the production prescription amount of the raw and auxiliary materials for each pot, namely anhydrous citric acid (8.47 kg), metronidazole (14.3 kg), lactose (15.4 kg), sodium carboxymethyl starch (1.75 kg), hypromellose (6.23 kg), sodium bicarbonate (6.79 kg), sodium lauryl sulfate (0.35 kg); a total of three pots are weighed. Additionally, weigh polyvinylpyrrolidone K30 (0.84 kg) for standby.

[0037] Dissolve the weighed polyvinylpyrrolidone K30 (0.84 kg) in absolute ethanol (13.15 kg) to obtain a 6% polyvinylpyrrolidone K30 absolute ethanol solution.

[0038] Add the weighed raw and auxiliary materials into the trough mixer by pot, stir for 40 minutes, and then add 4.66 kg / pot of 6% polyvinylpyrrolidone K30 absolute ethanol solution (4.66 kg of 6% polyvinylpyrrolidone K30 absolute ethanol solution contains 0.28 kg of polyvinylpyrrolidone K30 and 4.38 kg of absolute ethanol). After mixing for 15 minutes, make soft materials, and use a 30-mesh sieve in a rocking granulator to make granules and spread them on a baking tray, with about 2 - 3 kg loaded on each tray, and then load them into the oven cart. Push the oven cart into the hot air circulation oven, set the drying temperature at 50 °C, after drying for 1.5 hours, stop supplying steam, and screen the granules after cooling.

[0039] Place the dried and cooled granules in a rocking granulator for screening. The screening sieve is 30-mesh. After screening, spread them on a baking tray, with about 2 - 3 kg loaded on each tray, and then load them into the oven cart. Push it into the hot air circulation oven, set the drying temperature at 50 °C, after drying for 2 hours, measure the moisture content of the granules ≤ 0.5% (when the measurement temperature is 50 °C) (measured by a rapid moisture analyzer). After the moisture inspection is qualified, stop supplying steam, and after cooling, pack them in a clean film bag and seal for standby.

[0040] Put the granules obtained after screening into a multi-directional motion mixer, and then add the prescribed amount of magnesium stearate (2.10 kg), and run the multi-directional motion mixer for 20 minutes to mix them evenly. Collect the granules after total mixing and pack them in a clean transfer barrel.

[0041] Disinfect the tablet press with 75% ethanol wipe. After debugging the tablet press to run normally, adjust the tablet weight to 0.737 - 0.813 g to adjust the content of the active ingredient and thus adjust the drug effect; the tablet pressing pressure is 30 - 40 KN to ensure that it can be pressed into shape; the tablet thickness is 4.0 - 4.1 mm to adjust the surface area to ensure rapid dissolution and thus rapid onset of action.

[0042] During formal tablet pressing, first add the granules to be pressed into the hopper; during the tablet pressing process, check the tablet weight every 30 minutes to ensure that the tablet weight difference is within the range of 0.737 - 0.813 g, and check the appearance of the tablets at any time.

[0043] Check and receive the composite aluminum foil and polyamide / aluminum / polyvinyl chloride cold stamping formed solid medicinal composite hard tablets, adjust the heat sealing temperature of the packaging machine to 180 °C - 230 °C, the character heating temperature to 80 °C - 100 °C, and the running speed to 25 - 35 strokes / minute. First run the packaging materials empty to check the flatness and heat sealing situation. After it is normal, add metronidazole vaginal effervescent tablets to the hopper of the inner packaging product for production.

[0044] During the inner packaging process, the packaging quality (number of tablets loaded, heat-sealing tightness, wrinkles, holes, broken tablets, foreign matters, batch number, expiration date) shall be inspected every 30 minutes. After packaging is completed, the medicine plates shall be loaded into the transfer basket.

[0045] The tablets prepared by the production device and production method of the metronidazole vaginal effervescent tablets can quickly disintegrate by the combination of anhydrous citric acid, sodium carboxymethyl starch and sodium bicarbonate. On the one hand, the quick disintegration can quickly release metronidazole and act on the focus to resolve inflammation rapidly. On the other hand, the quick disintegration can quickly dissolve the tablets into a solution and quickly eliminate the foreign body sensation. The aluminum foil packaging can isolate the air from the tablets and prevent the tablets from absorbing moisture. It solves the problems of slow onset and long-term foreign body sensation existing in the existing effervescent tablets due to the existence of the coating layer.

Claims

1. A production method of metronidazole vaginal effervescent tablets, characterized in that: It includes the following steps: 1) Crushing of raw and auxiliary materials Crush anhydrous citric acid through the crusher of the metronidazole vaginal effervescent tablet production device, and pass through an 80-mesh sieve to crush it into fine powder for standby; 2) Drying of raw and auxiliary materials Prepare materials by weighing 2 - 5% more of the material amount after drying the moisture of raw and auxiliary materials according to the production prescription amount; Pass sodium bicarbonate and sodium lauryl sulfate through a hot air circulation oven respectively, set the drying temperature at 50°C, dry for 5 hours, and seal for standby; Pass anhydrous citric acid, metronidazole, lactose, sodium carboxymethyl starch, and hypromellose through a hot air circulation oven respectively, set the drying temperature at 70°C, dry for 5 hours, and seal for standby; 3) Weighing Weigh one-third of the raw and auxiliary materials of the production prescription amount per pot, weigh anhydrous citric acid, metronidazole, lactose, sodium carboxymethyl starch, hypromellose, sodium bicarbonate, sodium lauryl sulfate, and weigh polyvinylpyrrolidone K30 for standby; 4) Granulation Dissolve the weighed polyvinylpyrrolidone K30 in absolute ethanol to prepare a 6% polyvinylpyrrolidone K30 absolute ethanol solution; Add the weighed raw and auxiliary materials to the trough mixer by pot, stir for 40 minutes, then add the 6% polyvinylpyrrolidone K30 absolute ethanol solution, and mix for 15 minutes to make soft materials; Make granules with a 30-mesh sieve in a rocking granulator, spread them on a baking tray, and pass through a hot air circulation oven, set the drying temperature at 50°C, dry for 1.5 hours, and screen the granules after cooling; Place the dried and cooled granules in a rocking granulator for screening, the screening mesh is 30 meshes, after screening, pass through a hot air circulation oven, set the drying temperature at 50°C, and dry for 2 hours; 5) Total mixing Put the granules obtained after screening into a multi-directional motion mixer, and then add magnesium stearate, put it into the multi-directional motion mixer and mix for 20 minutes to make it evenly mixed for standby; 6) Tabletting After adjusting the parameters of the tabletting machine, tablet the granules obtained from total mixing through the tabletting machine; 7) Packaging The packaging machine wraps and packages the tablets with aluminum foil.

2. The production method of a metronidazole vaginal effervescent tablet according to claim 1, characterized in that: The raw material ratio (weight ratio) of the production prescription in step 3) is: anhydrous citric acid: metronidazole: lactose: sodium carboxymethyl starch: hypromellose: sodium bicarbonate: sodium lauryl sulfate: magnesium stearate = 1:1.69:1.82:0.21:0.74:0.8:0.04:0.

25.

3. The production method of a metronidazole vaginal effervescent tablet according to claim 1, characterized in that: The dosage of the 6% polyvinylpyrrolidone K30 absolute ethanol solution in step 4) is 4.66 kg / pot.

4. The production method of a metronidazole vaginal effervescent tablet according to claim 1, characterized in that: The adjusted parameters in step 6) include tablet weight, tabletting pressure, and tablet thickness. The tablet weight is 0.737 - 0.813 g, the tabletting pressure is 30 - 40 KN, and the tablet thickness is 4.0 - 4.1 mm.

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