CN105055350A - Preparation method of proton pump inhibitor-containing tablet - Google Patents
Preparation method of proton pump inhibitor-containing tablet Download PDFInfo
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- CN105055350A CN105055350A CN201510474015.6A CN201510474015A CN105055350A CN 105055350 A CN105055350 A CN 105055350A CN 201510474015 A CN201510474015 A CN 201510474015A CN 105055350 A CN105055350 A CN 105055350A
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- Prior art keywords
- particle size
- mixing
- proton pump
- pump inhibitor
- diluent
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- 239000000612 proton pump inhibitor Substances 0.000 title claims abstract description 32
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Landscapes
- Medicinal Preparation (AREA)
Abstract
The invention relates to the technical field of medicine preparations and concretely relates to a preparation method of a proton pump inhibitor-containing tablet. The proton pump inhibitor-containing tablet is prepared from controlled release pellets, diluents, a disintegrating agent and a lubricant by a direct tabletting method. The preparation method comprises 1, preparing pellet cores for carrying drugs, 2, preparing isolation pellets, 3, preparing controlled release pellets, 4, carrying out mixing and sieving to obtain a material, and 5, carrying out direct tabletting, wherein in the step 4, a diluent with small particle sizes and the controlled release pellets are mixed and then the mixture and a diluent with big particle sizes are mixed, and the diluents with small and big particle sizes are respectively selected from one or more of cellulose materials. The preparation method solves the problem of poor content uniformity of the existing controlled release pellet roundness excess direct tabletting method so that tablet quality is guaranteed.
Description
Technical Field
The invention relates to the technical field of pharmaceutical preparations, in particular to a preparation method of a tablet containing a proton pump inhibitor.
Background
Oral sustained-release preparations are increasingly becoming more prominent in the field of pharmacy because of their unique advantages. The oral sustained and controlled release preparation with multiple units is a novel pharmaceutical preparation technology developed in the present year. Because the irritation to mucosa at an absorption part due to overhigh local medicine concentration can be effectively avoided, the toxic and side effects are reduced, the medicine absorption is improved, and the bioavailability is improved; ensuring the safety of medication and avoiding dose burst release; reducing intra-and inter-individual variability due to eating and gastric emptying, etc.
The multiple unit oral controlled release formulation allows the active agent to be delivered intact to the gastrointestinal site where it can be rapidly absorbed, protecting the drug from the stomach acid.
Various types of controlled release formulations of multiple unit dosage forms are disclosed in the prior art, and the preparation process employs a pellet compression technique. However, various problems arise when pellets coated with a controlled release coating are compressed into tablets. For example, functional protective garments break down after compression, causing them to be damaged by the penetrating gastrointestinal fluids. In addition, the pellet has high roundness and excessive fluidity, and the problem of content uniformity of the product caused by material layering is easy to occur in the tabletting process.
Patent document CN95190819.7 discloses a multiple unit pharmaceutical formulation containing a proton pump inhibitor. The preparation is prepared into drug-loaded pellet cores by blank pellet core bottom spray coating technology or extrusion and rounding, controlled release pellets are obtained by bottom spray coating, and then the drug-loaded pellet cores are mixed with tabletting auxiliary materials or blank granules for tabletting. The controlled release pellets prepared by the bottom spray coating technology have high roundness, and the content uniformity problem can occur after the controlled release pellets are simply mixed with microcrystalline cellulose. In the extrusion spheronization method, microcrystalline cellulose which is a plastic material is adopted to improve the toughness of the pellets, but the extrusion spheronization process is complex, has various influencing factors and low yield of useful pellets, and particularly the particle size distribution of the prepared pellets can have great influence on the product quality and is not beneficial to the quality control of commercial mass production. In addition, the pellets are protected from crushing during the tableting process by the blank granules. Because some factors need to be judged by experience, the product quality is unstable, the batch-to-batch difference is large, and the like.
Therefore, there is a need for a tabletting method and corresponding formulation that overcomes the above-mentioned drawbacks of the prior art, and that is simple in manufacturing process, low in cost, satisfactory in product quality and stable.
Disclosure of Invention
In view of the above deficiencies of the prior art, it is an object of the present invention to provide a process for the preparation of tablets containing a proton pump inhibitor. The inventors have found unexpectedly in experiments that, for proton pump inhibitors, the tablets obtained by direct compression using the preparation method of the present invention can completely improve the defects of the tablets of the prior art; the tablet prepared by the preparation method can stably release active ingredients and completely transmit the active ingredients to an absorption part; not only obviously reduces the production cost, but also improves the bioavailability and the stability of the medicine, and overcomes the problem of poor content uniformity in the preparation of the controlled release pellet by a direct tabletting method with excessive roundness, so that the quality of the tablet is ensured.
In order to achieve the above object, the present invention provides a method for preparing a tablet containing a proton pump inhibitor, wherein the tablet is prepared from the following components by mass percent through a direct compression method:
the preparation method comprises the following steps:
(1) coating a proton pump inhibitor on the surface of a blank pill core to prepare a medicine-carrying pill core; wherein the mass ratio of the proton pump inhibitor to the blank pill core is 0.4-1: 1;
(2) preparing isolation pellets for the isolating coat of the pill carrying core; the weight of the isolation clothes is 40-60% of the weight of the drug-loaded pill core;
(3) coating the isolating pellets with enteric coating to prepare controlled release pellets; the weight of the enteric coating is 55 to 75 percent of the weight of the isolating pellets;
(4) mixing and sieving the controlled release pellets, the diluent, the disintegrant and the lubricant to obtain a material;
(5) directly tabletting the above materials to obtain the tablet;
in the step (4), the mixing is to mix the diluent with smaller particle size and the controlled release pellets; mixing the mixture with diluent with larger particle size; the thinner with smaller particle size and the thinner with larger particle size are selected from one or more than one of celluloses.
Preferably, in the step (4), the mixing is specifically:
mixing the controlled-release pellets, the diluent with smaller particle size and the disintegrating agent, sieving to obtain a mixture, mixing the mixture and the diluent with larger particle size, and then mixing the mixture and the sieved lubricant to obtain a material; or,
mixing the controlled-release pellets with a diluent with a small particle size, sieving to obtain a mixture, mixing the mixture, the diluent with a large particle size and a disintegrating agent, and then mixing with a sieved lubricant to obtain a material.
Preferably, the diluent having a small particle size and the diluent having a large particle size are both microcrystalline cellulose (preferably, they can be directly tabletted).
More preferably, the diluent with smaller particle size is microcrystalline cellulose PH 101; the diluent with larger grain diameter is microcrystalline cellulose PH 200.
More preferably, the particle size of the microcrystalline cellulose PH101 is 30-50 μm; the particle size of the microcrystalline cellulose PH200 is 180-200 μm.
Preferably, the mass ratio of the microcrystalline cellulose PH101 to the microcrystalline cellulose PH200 is 1: 0.4-4.
More preferably, the mass ratio of the microcrystalline cellulose PH101 to the microcrystalline cellulose PH200 is 1: 0.5-3.
In one embodiment, the mass ratio of microcrystalline cellulose PH101 to microcrystalline cellulose PH200 is 1: 2.
The diluent with smaller particle size is based on the comparison of all selected diluents without influencing the proper flowability of the prescription.
Preferably, in the step of mixing the diluent with the small particle size and the controlled-release pellets, the mixing time is 5-20 minutes, and the mixing speed is 5-30 revolutions per minute. Preferably, the mixing time is 10-15 minutes, and the mixing speed is 10-25 revolutions per minute. In one embodiment of the invention, the mixing time is 10 minutes and the mixing speed is 10 revolutions per minute.
Preferably, in the step of mixing the mixture with the diluent with a large particle size, the mixing time is 5 to 20 minutes, and the mixing speed is 5 to 30 revolutions per minute. Preferably, the mixing time is 10-15 minutes, and the mixing speed is 10-25 revolutions per minute. In one embodiment of the invention, the mixing time is 15 minutes and the mixing speed is 10 revolutions per minute.
The invention selects diluents with different particle sizes, and aims to wrap the controlled-release pellets by the diluent with smaller particle size (such as microcrystalline cellulose PH101) and mix the controlled-release pellets with other auxiliary materials to ensure the content and content uniformity of the tablets.
In the step (4), the size of the screen used for sieving can smoothly sieve the controlled release pellets; preferably, a mesh larger than the particle size of the controlled release pellets is used; in one embodiment of the invention, a mesh slightly larger than the particle size of the controlled release pellets is used.
The mixing may be by adding the materials to a mixer for mixing.
Preferably, the lubricant is sieved in advance, and the sieve is generally 16-30 meshes, preferably 16-25 meshes, and more preferably 20 meshes.
Preferably, in the step (5), the tabletting pressure is properly adjusted, so that the friability of the pressed tablets is qualified, and the problem of cracking of the products in the transportation process is avoided.
The blank pellet core is well known in the technical field, and can adopt sucrose pellet cores, sucrose starch pellet cores, lactose pellet cores and the like, and preferably adopts sucrose pellet cores.
The particle size of the blank pellet core is 0.20-0.36 mm, and preferably 0.212-0.355 mm.
Preferably, the mass ratio of the proton pump inhibitor to the blank pill core is 0.8-1: 1; more preferably 1: 1.
Preferably, in the step (1), the proton pump inhibitor is dissolved or suspended in the binder solution to prepare a solution or a suspension, and the solution or the suspension is coated on the blank pellet core by a bottom spray coating method; the adhesive is hypromellose (preferably hypromellose E5). The binder solution is an aqueous solution, preferably having a concentration of 5% (W/V).
For multiple unit formulations, the problem of tablet content uniformity can be difficult to overcome if direct compression is used. The invention ensures the content uniformity of the tablet prepared by the direct powder compression method by selecting the material with proper fluidity and a proper mixing mode.
The term "suitable flowability" generally means that the powder mixture flows rapidly and uniformly so as to be uniformly filled in the die.
In particular, the material of the invention with suitable flowability has the composition and formulation as described above.
The term "suitable mixing means" generally means that mixing means is used in such a way that the content uniformity of the resulting tablets is as desired or at a higher level.
For the tablet, in order to prevent the controlled release pellets from having excessive fluidity, a step-by-step mixing method is adopted, namely microcrystalline cellulose with smaller particle size is used for wrapping the controlled release pellets, so that the influence on the content uniformity caused by the uneven distribution of the controlled release pellets is avoided. In addition, the microcrystalline cellulose with larger grain diameter bears certain pressure during tabletting, thereby ensuring that the controlled release pellet is not crushed, and improving the pressure resistance and good stability of the controlled release pellet.
In the mixing process, the invention also adopts a sieving method to sieve the pre-mixed material to prevent the fine powder from bonding, so that the controlled release pellets are better dispersed and the content uniformity of the pressed tablets is good.
The active ingredient in the tablets of the invention is a proton pump inhibitor, which is mainly used for the treatment of gastric acid related disorders of the digestive system, such as the known names lansoprazole, pantoprazole, omeprazole or esomeprazole, etc. But due to the existence of sulfoxide groups in the structure, the material is extremely sensitive in an acidic medium and is easily and rapidly degraded by catalysis of an acidic compound.
In order to isolate the active ingredients from reacting with the acidic enteric coating material, influence the stability, simultaneously improve the toughness of the controlled release pellet and ensure that the product has good acid resistance, the invention carries out the step of coating the enteric coating (controlled release coating film layer) before the drug-loaded pellet core is coated with the enteric coating.
The material of the barrier coat is a coating material/binder and optionally an anti-tack agent. The material of the barrier coating is not limited, and may be one or more of the coating materials commonly used in the art, such as hypromellose, povidone, hydroxypropyl cellulose, ethyl cellulose, etc. with low viscosity. And optionally adding conventional antisticking agent such as one or more of pulvis Talci, glyceryl stearate, silicon dioxide and magnesium stearate.
The coating material for the barrier coat and the antisticking agent are not limited in their amounts, and may be those conventionally used in the art. Preferably, the weight ratio of the coating material to the anti-sticking agent is 8-10: 17.5.
Preferably, the isolation layer comprises a coating material and an anti-sticking agent; the coating material is hydroxypropyl methylcellulose E5, and the antisticking agent is pulvis Talci and magnesium stearate.
Preferably, the weight of the barrier coat is 45% to 55%, more preferably about 50% of the weight of the medicated pellet core.
The components of the enteric coating are well known in the art and generally include enteric materials, plasticizers, anti-tacking agents, surfactants, and the like. It is also common knowledge in the art that these components, such as plasticizers and surfactants, need to be added or not depending on the choice of enteric material. The enteric material, plasticizer, anti-sticking agent, surfactant, etc. may be any known in the art.
Preferably, the enteric material comprises acrylic resin, phthalic acid cellulose acetate, hydroxypropyl methyl cellulose phthalate, polyvinyl alcohol phthalate, cellulose acetate trimellitate, shellac and the like; the plasticizer can be citric acid esters, phthalic acid esters or phosphoric acid esters; the antisticking agent can be magnesium stearate or glyceryl monostearate, etc.; the surfactant is Tween-80 or sodium dodecyl sulfate. More preferably, the weight ratio of the enteric material to the plasticizer to the anti-sticking agent to the surfactant is 100: 20-30: 2.5-10: 1-3.
Preferably, the enteric material is polyacrylic resin latex, the plasticizer is triethyl citrate, the anti-sticking agent is glycerol monostearate, and the surfactant is tween-80.
Preferably, the weight of the enteric coating is between 60% and 70% of the weight of the spacer pellets, more preferably about 65%.
The disintegrant may be one or more of croscarmellose sodium, sodium carboxymethyl starch, and crospovidone.
The lubricant may be one or more of magnesium stearate, stearic acid, sodium laurate fumarate, talc and colloidal silicon dioxide.
Preferably, the tablet is prepared from the following components in percentage by mass by a direct compression method:
in the step (1), the mass ratio of the proton pump inhibitor to the blank pill core is 0.8-1: 1;
in the step (2), the weight of the isolation coat is 45-55% of that of the drug-loaded pill core; the weight ratio of the coating material to the anti-sticking agent is 8-10: 17.5;
in the step (3), the weight of the enteric coating is 60-70% of the weight of the isolation pellets; the weight ratio of the enteric material to the plasticizer to the antisticking agent to the surfactant is 100: 20-30: 2.5-10: 1-3.
In the step (4), the mass ratio of the microcrystalline cellulose PH101 to the microcrystalline cellulose PH200 is 1: 0.5-3.
More preferably, the tablet is prepared by a direct compression method from the following components in percentage by mass:
in the step (1), the blank pellet core is a sucrose blank pellet core, and the particle size is 0.212-0.355 mm; the mass ratio of the proton pump inhibitor to the blank pill core is 1: 1; the adhesive used for wrapping is hydroxypropyl methylcellulose E5;
in the step (2), the weight of the isolation clothes is 50% of that of the drug-loaded pill core; the coating material is hydroxypropyl methylcellulose E5, and the antisticking agent is talcum powder and magnesium stearate;
in step (3), the weight of the enteric coating is 65% of the weight of the spacer pellets; the enteric material is polyacrylic resin emulsion; the plasticizer is triethyl citrate; the anti-sticking agent is glyceryl monostearate and distearate; the surfactant is tween-80;
in the step (4), the disintegrant is crospovidone; the lubricant is magnesium stearate; the mass ratio of the microcrystalline cellulose PH101 to the microcrystalline cellulose PH200 is 1: 2;
in the step (5), the hardness of the tablet is maintained at 80N-100N.
In one embodiment, the tablet is prepared from the following components in percentage by mass by a direct compression method:
in addition, the present invention provides a tablet containing a proton pump inhibitor, which is prepared by the above-described preparation method.
According to the preparation method of the powder direct compression method, the obtained tablet has the following advantages:
1. the prescription and the preparation method of the tablet provided by the invention supplement each other, influence each other and cooperate with each other, and the problem of excessive fluidity of the controlled release pellets is effectively controlled, so that the influence on the content uniformity of the product caused by the uneven distribution of the controlled release pellets is avoided, and the effectiveness and the safety of the product are further influenced.
2. The preparation method is simple and beneficial to industrial mass production, has high reproducibility, and the obtained product preparation has the advantage of good drug stability.
3. The tablet provided by the invention has good compressibility, the hardness of the tablet is not influenced by the difference of the production capacity of equipment, and the integrity of the tablet in the transportation process is effectively ensured.
4. The preparation method of the tablet does not use organic solvents, and all the used auxiliary materials are easy to obtain, low in price and low in cost.
Detailed Description
Those skilled in the art can modify the process parameters appropriately to achieve the desired results with reference to the disclosure herein. It is expressly intended that all such similar substitutes and modifications apparent to those skilled in the art are deemed to be included within the invention. While the products and methods of this invention have been described in terms of preferred embodiments, it will be apparent to those of skill in the art that variations and modifications, or appropriate alterations and combinations, of the methods and applications described herein may be made to implement and utilize the techniques of this invention without departing from the spirit and scope of the invention.
The process for preparing the tablet provided by the present invention is further described below.
EXAMPLE 1 direct powder compression method for making tablets
A commercially available blank pellet core was used, the formulation of which is shown in table 1:
table 1: tablet (microcrystalline cellulose content 62%) formulation
Placing the blank pellet core in a fluidized bed (bottom spraying) coating device, taking 5% (W/V) hydroxypropyl methylcellulose E5 aqueous solution as an adhesive, weighing the active ingredient lansoprazole according to the prescription amount, adding the lansoprazole into the hydroxypropyl methylcellulose aqueous solution, and carrying out fluidization medicine feeding under the condition of continuous stirring, wherein the material temperature is maintained at 35-45 ℃, the air inlet temperature is not higher than 90 ℃, and the atomization pressure is 0.15-0.20 Mpa; obtaining the drug-loaded pill core.
Weighing hydroxypropyl cellulose with the prescription amount, preparing a solution with the content of 5% by taking water as a solvent, and sequentially adding magnesium stearate and talcum powder under the state of continuous stirring. Continuously stirring the prepared coating solution, and spraying the coating solution on the drug-loaded pill core by using a spray gun, wherein the material temperature is maintained at 35-45 ℃, the air inlet temperature is not higher than 90 ℃, and the atomization pressure is 0.15-0.20 Mpa; obtain the release pellets.
Adding tween-80 into water, stirring, adding glyceryl monostearate and distearate, and stirring; weighing triethyl citrate, adding into a proper amount of water, and homogenizing; pouring into Tween-80 solution, and slowly pouring into polyacrylic resin emulsion under stirring. Coating the isolated pellets in a fluidized bed, wherein the material temperature is maintained at 25-35 ℃, the air inlet temperature is not higher than 60 ℃, and the atomization pressure is 0.15-0.20 Mpa; obtaining the controlled release pellet.
Adding microcrystalline cellulose PH101 (the particle size is 30-50 mu m) and the obtained controlled-release pellets into a mixer, and mixing for 10 minutes at the mixing speed of 10 revolutions per minute; sieving the mixture with a 20-mesh sieve, adding the sieved mixture, microcrystalline cellulose PH200 (the particle size is 180-200 mu m) and crospovidone into a mixer, and mixing for 15 minutes at the mixing speed of 10 revolutions per minute; adding the magnesium stearate which is sieved by the 20-mesh sieve into the mixer, and continuously mixing for 5 minutes at the mixing speed of 10 revolutions per minute; and (5) obtaining a material.
And (3) putting the materials into a tablet machine for direct tabletting, and adjusting the pressure to maintain the hardness of the tablet at 80-100N to obtain the tablet.
EXAMPLE 2 preparation of tablets by direct compression of powders
The prescription is shown in table 2:
table 2: tablet (microcrystalline cellulose content 70%) formula
Tablets were prepared using the same procedure as in example 1.
EXAMPLE 3 direct powder compression Process for preparation of tablets
The prescription is shown in table 3:
table 3: tablet (microcrystalline cellulose content 60%) formula
The same process as in example 1 was used to prepare tablets, except that the following steps were different from the preparation process of example 1:
adding microcrystalline cellulose PH101 (the particle size is 30-50 mu m), crospovidone and the obtained controlled-release pellets into a mixer, and mixing for 10 minutes at the mixing speed of 10 revolutions per minute; sieving the mixture with a 20-mesh sieve, adding the sieved mixture and microcrystalline cellulose PH200 (the particle size is 180-200 mu m) into a mixer, and mixing for 15 minutes at the mixing speed of 10 revolutions per minute; adding the magnesium stearate which is sieved by the 20-mesh sieve into the mixer, and continuously mixing for 5 minutes at the mixing speed of 10 revolutions per minute; and (5) obtaining a material.
EXAMPLE 4 direct powder compression method for preparing tablets
A commercially available blank pellet core was used, the formulation of which is shown in table 4:
table 4: tablet (microcrystalline cellulose content 62%) formulation
Tablets were prepared using the same procedure as in example 1.
Comparative example 1
Tablets were prepared using the same formulation and procedure as in example 1, except that the following steps were different from the preparation procedure of example 1:
adding microcrystalline cellulose PH101, microcrystalline cellulose PH200, crospovidone and controlled release pellets into a mixer, and mixing for 10 minutes at a mixing speed of 10 revolutions per minute; then adding magnesium stearate into the mixer, and continuously mixing for 5 minutes at the mixing speed of 10 revolutions per minute; and (5) obtaining a material.
Experimental example 1 acid resistance of tablets of examples 1 to 4 and comparative example 1
The acid resistance is determined by measuring the content of the drug which is not released because the active ingredient is decomposed in the acid and the release amount of the active ingredient in the acid cannot be directly measured. Taking each sample, according to a release rate determination method (XD second method in appendix II of the second part of the version 2010 of Chinese pharmacopoeia), taking 750mL of hydrochloric acid solution as a solvent, rotating at 100 revolutions per minute, stopping after 2 hours, taking out tablets, and detecting the content.
TABLE 5 acid resistance content measurement results
Experimental example 2 determination of content uniformity of tablets of examples 1, 2, 4 and comparative example 1
Taking 10 tablets of the products of examples 1, 2 and 4 and comparative example 1, respectively placing the 10 tablets into a 20mL measuring flask, measuring according to an XE content uniformity measuring method in the appendix of Chinese pharmacopoeia 2010, and calculating the content:
table 6: content uniformity of tablets
*: the size of A +1.80S indicates how good the content uniformity of the tablets is. S is the standard deviation of the relative content of 10 tablets;
a is the absolute value of the difference between the indicated quantity and the mean.
As can be seen from Table 6, when the content of microcrystalline cellulose is 60-70%, the content uniformity of the compressed tablets obtained by distributing, mixing and sieving microcrystalline cellulose with different particle sizes is good, and the A +1.80S value is lower than 10.50. After microcrystalline cellulose with different particle sizes is mixed with the controlled release pellets, the value of A +1.80S of the compressed tablets is larger than the value of the step-by-step mixing step.
Therefore, when the multi-unit preparation is pressed by a direct tabletting method, and the content of microcrystalline cellulose is 60-70%, the content uniformity of the pressed tablet obtained by mixing and sieving microcrystalline cellulose with different particle sizes step by step is good.
Experimental example 3 storage stability assay
The tablets of example 1 were packaged in double aluminium and analysed for impurity content by HPLC after 6 months at 40 ℃/RH 75%.
TABLE 7 content of impurities
| Example 1 | |
| Total miscellaneous content (%) | 0.00 |
Table 7 shows that the product quality of example 1 is constant in the storage stability assay, indicating that the barrier coating has good barrier effect, the enteric coating with sufficient thickness is beneficial to the toughness of the controlled release pellet, is not easy to crush under pressure, and the formulation and preparation method thereof can ensure the product stability.
Claims (10)
1. The preparation method of the tablet containing the proton pump inhibitor is characterized in that the tablet is prepared by a direct compression method from the following components in percentage by mass:
the preparation method comprises the following steps:
(1) coating a proton pump inhibitor on the surface of a blank pill core to prepare a medicine-carrying pill core; wherein the mass ratio of the proton pump inhibitor to the blank pill core is 0.4-1: 1;
(2) preparing isolation pellets for the isolating coat of the pill carrying core; the weight of the isolation clothes is 40-60% of the weight of the drug-loaded pill core;
(3) coating the isolating pellets with enteric coating to prepare controlled release pellets; the weight of the enteric coating is 55 to 75 percent of the weight of the isolating pellets;
(4) mixing and sieving the controlled release pellets, the diluent, the disintegrant and the lubricant to obtain a material;
(5) directly tabletting the above materials to obtain the tablet;
in the step (4), the mixing is to mix the diluent with smaller particle size and the controlled release pellets; mixing the mixture with diluent with larger particle size;
the thinner with smaller particle size and the thinner with larger particle size are selected from one or more than one of celluloses.
2. The process for preparing a tablet containing a proton pump inhibitor as set forth in claim 1, wherein in the step (4), the mixing is:
mixing the controlled-release pellets, the diluent with smaller particle size and the disintegrating agent, sieving to obtain a mixture, mixing the mixture and the diluent with larger particle size, and then mixing the mixture and the sieved lubricant to obtain a material; or,
mixing the controlled-release pellets with a diluent with a small particle size, sieving to obtain a mixture, mixing the mixture, the diluent with a large particle size and a disintegrating agent, and then mixing with a sieved lubricant to obtain a material.
3. The method for producing a tablet containing a proton pump inhibitor as claimed in claim 1 or 2, wherein the diluent having a small particle size and the diluent having a large particle size are both microcrystalline cellulose; preferably, the diluent with the smaller particle size is microcrystalline cellulose PH101, and the diluent with the larger particle size is microcrystalline cellulose PH 200.
4. The method for preparing a tablet containing a proton pump inhibitor as claimed in claim 3, wherein the particle size of the microcrystalline cellulose PH101 is 30 to 50 μm, and the particle size of the microcrystalline cellulose PH200 is 180 to 200 μm; the mass ratio of the microcrystalline cellulose PH101 to the microcrystalline cellulose PH200 is 1: 0.4-4.
5. The process for producing a tablet containing a proton pump inhibitor according to claim 1,
in the step (1), the particle size of the blank pellet core is 0.20-0.36 mm; the proton pump inhibitor is lansoprazole, pantoprazole, omeprazole or esomeprazole; the blank pellet core is a sucrose pellet core, a sucrose starch pellet core or a lactose pellet core;
in the step (2), the isolation coating comprises a coating material and an anti-sticking agent; the coating material is one or more of low-viscosity hypromellose, povidone, hydroxypropyl cellulose and ethyl cellulose; the antisticking agent is one or more of talcum powder, stearin, silicon dioxide and magnesium stearate;
in the step (3), the enteric coating comprises an enteric material, a plasticizer, an anti-sticking agent and a surfactant; the enteric material is acrylic resin, phthalic acid cellulose acetate, hydroxypropyl methyl cellulose phthalate, polyvinyl alcohol phthalate, cellulose acetate trimellitate or shellac; the plasticizer is citrate, phthalate or phosphate; the antisticking agent is magnesium stearate or glyceryl monostearate; the surfactant is tween-80 or sodium dodecyl sulfate;
in the step (4), the disintegrating agent is one or more of croscarmellose sodium, sodium carboxymethyl starch and crospovidone; the lubricant is one or more of magnesium stearate, stearic acid, sodium laurate fumarate, talc and colloidal silicon dioxide.
6. The process for producing a tablet containing a proton pump inhibitor according to claim 1,
in the step of mixing the diluent with the smaller particle size and the controlled-release pellets, the mixing time is 5-20 minutes, and the mixing speed is 5-30 revolutions per minute;
in the step of mixing the mixture with the diluent with larger particle size, the mixing time is 5-20 minutes, and the mixing speed is 5-30 revolutions per minute;
the lubricant is sieved in advance, and the screen is 16-30 meshes.
7. The method for preparing a tablet containing a proton pump inhibitor according to claim 1 or 5, wherein the tablet is prepared by a direct compression method from the following components in percentage by mass:
8. the process for preparing a tablet containing a proton pump inhibitor according to claim 7,
in the step (1), the mass ratio of the proton pump inhibitor to the blank pill core is 0.8-1: 1;
in the step (2), the weight of the isolation coat is 45-55% of that of the drug-loaded pill core; the weight ratio of the coating material to the anti-sticking agent is 8-10: 17.5;
in the step (3), the weight of the enteric coating is 60-70% of the weight of the isolation pellets; the weight ratio of the enteric material to the plasticizer to the anti-sticking agent to the surfactant is 100: 20-30: 2.5-10: 1-3;
in the step (4), the mass ratio of the microcrystalline cellulose PH101 to the microcrystalline cellulose PH200 is 1: 0.5-3.
9. The method for preparing a tablet containing a proton pump inhibitor according to claim 1 or 8, wherein the tablet is prepared by a direct compression method from the following components in percentage by mass:
in the step (1), the blank pellet core is a sucrose blank pellet core, and the particle size is 0.212-0.355 mm; the mass ratio of the proton pump inhibitor to the blank pill core is 1: 1; the adhesive used for wrapping is hydroxypropyl methylcellulose E5;
in the step (2), the weight of the isolation clothes is 50% of that of the drug-loaded pill core; the coating material is hydroxypropyl methylcellulose E5, and the antisticking agent is talcum powder and magnesium stearate;
in step (3), the weight of the enteric coating is 65% of the weight of the spacer pellets; the enteric material is polyacrylic resin emulsion; the plasticizer is triethyl citrate; the anti-sticking agent is glyceryl monostearate and distearate; the surfactant is tween-80;
in the step (4), the disintegrant is crospovidone; the lubricant is magnesium stearate; the mass ratio of the microcrystalline cellulose PH101 to the microcrystalline cellulose PH200 is 1: 2;
in the step (5), the hardness of the tablet is maintained at 80N-100N.
10. The method for preparing a tablet containing a proton pump inhibitor according to claim 9, wherein the tablet is prepared by a direct compression method from the following components in percentage by mass:
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| CN108201527A (en) * | 2016-12-16 | 2018-06-26 | 广州共禾医药科技有限公司 | A kind of slow-release dry suspension comprising proton pump inhibitor and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN105796517A (en) * | 2016-03-22 | 2016-07-27 | 海南华益泰康药业有限公司 | Doxycycline hyclate enteric-coated tablet and preparation method thereof |
| CN105796517B (en) * | 2016-03-22 | 2019-04-26 | 海南华益泰康药业有限公司 | It is doxycycline hyclate enteric-coated a kind of and preparation method thereof |
| CN108201527A (en) * | 2016-12-16 | 2018-06-26 | 广州共禾医药科技有限公司 | A kind of slow-release dry suspension comprising proton pump inhibitor and preparation method thereof |
| CN106619550A (en) * | 2017-01-20 | 2017-05-10 | 海南华益泰康药业有限公司 | Enteric-coated orally disintegrating tablet containing lansoprazole and preparation method of enteric-coated orally disintegrating tablet |
| CN106619550B (en) * | 2017-01-20 | 2019-08-27 | 海南华益泰康药业有限公司 | A kind of enteric-coated orally disintegrating tablets agent and preparation method thereof containing Lansoprazole |
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Effective date of registration: 20190612 Address after: 210000 Longmian Avenue 568, High-tech Park, Jiangning District, Nanjing City, Jiangsu Province Patentee after: Nanjing Haijingkang Pharmaceutical Technology Co., Ltd. Address before: 571100 Haikou City, Hainan Province, 273 Nanhai Avenue Haikou High-tech Zone D light steel structure standard industrial plant west side Patentee before: Hainan Visum Pharmaceutical Co., Ltd. |