CN114306257A - Ciprofloxacin hydrochloride tablet and preparation method thereof - Google Patents
Ciprofloxacin hydrochloride tablet and preparation method thereof Download PDFInfo
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- CN114306257A CN114306257A CN202210045091.5A CN202210045091A CN114306257A CN 114306257 A CN114306257 A CN 114306257A CN 202210045091 A CN202210045091 A CN 202210045091A CN 114306257 A CN114306257 A CN 114306257A
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- 229960001229 ciprofloxacin hydrochloride Drugs 0.000 title claims abstract description 97
- DIOIOSKKIYDRIQ-UHFFFAOYSA-N ciprofloxacin hydrochloride Chemical compound Cl.C12=CC(N3CCNCC3)=C(F)C=C2C(=O)C(C(=O)O)=CN1C1CC1 DIOIOSKKIYDRIQ-UHFFFAOYSA-N 0.000 title claims abstract description 97
- 238000002360 preparation method Methods 0.000 title claims abstract description 32
- 239000002994 raw material Substances 0.000 claims abstract description 57
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims abstract description 54
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 claims abstract description 47
- 229960000913 crospovidone Drugs 0.000 claims abstract description 47
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 claims abstract description 47
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 claims abstract description 47
- 239000000843 powder Substances 0.000 claims abstract description 37
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims abstract description 27
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims abstract description 27
- 235000019359 magnesium stearate Nutrition 0.000 claims abstract description 27
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims abstract description 27
- 239000008108 microcrystalline cellulose Substances 0.000 claims abstract description 27
- 229940016286 microcrystalline cellulose Drugs 0.000 claims abstract description 27
- 239000000741 silica gel Substances 0.000 claims abstract description 27
- 229910002027 silica gel Inorganic materials 0.000 claims abstract description 27
- 238000000034 method Methods 0.000 claims abstract description 21
- 229920002261 Corn starch Polymers 0.000 claims abstract description 17
- 239000008120 corn starch Substances 0.000 claims abstract description 17
- 239000007888 film coating Substances 0.000 claims abstract description 17
- 238000009501 film coating Methods 0.000 claims abstract description 17
- 239000000463 material Substances 0.000 claims description 105
- 239000011248 coating agent Substances 0.000 claims description 60
- 238000000576 coating method Methods 0.000 claims description 60
- 238000007873 sieving Methods 0.000 claims description 36
- 238000005303 weighing Methods 0.000 claims description 30
- 238000004080 punching Methods 0.000 claims description 20
- 239000002245 particle Substances 0.000 claims description 16
- 239000008187 granular material Substances 0.000 claims description 12
- 239000000203 mixture Substances 0.000 claims description 11
- 229920002472 Starch Polymers 0.000 claims description 10
- 238000010438 heat treatment Methods 0.000 claims description 10
- 230000002572 peristaltic effect Effects 0.000 claims description 10
- 239000008213 purified water Substances 0.000 claims description 10
- 239000007787 solid Substances 0.000 claims description 10
- 229910001220 stainless steel Inorganic materials 0.000 claims description 10
- 239000010935 stainless steel Substances 0.000 claims description 10
- 239000008107 starch Substances 0.000 claims description 10
- 235000019698 starch Nutrition 0.000 claims description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 10
- 230000004584 weight gain Effects 0.000 claims description 10
- 235000019786 weight gain Nutrition 0.000 claims description 10
- 239000007788 liquid Substances 0.000 claims description 8
- 238000004090 dissolution Methods 0.000 abstract description 9
- 239000003814 drug Substances 0.000 abstract description 4
- 238000010521 absorption reaction Methods 0.000 abstract description 3
- 238000000338 in vitro Methods 0.000 abstract description 2
- 238000001727 in vivo Methods 0.000 abstract description 2
- 238000005469 granulation Methods 0.000 description 3
- 230000003179 granulation Effects 0.000 description 3
- 239000003674 animal food additive Substances 0.000 description 2
- 239000002131 composite material Substances 0.000 description 2
- 230000001186 cumulative effect Effects 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 206010067484 Adverse reaction Diseases 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- KYGZCKSPAKDVKC-UHFFFAOYSA-N Oxolinic acid Chemical group C1=C2N(CC)C=C(C(O)=O)C(=O)C2=CC2=C1OCO2 KYGZCKSPAKDVKC-UHFFFAOYSA-N 0.000 description 1
- 206010057190 Respiratory tract infections Diseases 0.000 description 1
- 206010062255 Soft tissue infection Diseases 0.000 description 1
- 208000037386 Typhoid Diseases 0.000 description 1
- 206010000059 abdominal discomfort Diseases 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000003306 quinoline derived antiinfective agent Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 201000008297 typhoid fever Diseases 0.000 description 1
- 210000002229 urogenital system Anatomy 0.000 description 1
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Abstract
The invention discloses a ciprofloxacin hydrochloride tablet and a preparation method thereof, wherein the ciprofloxacin hydrochloride tablet comprises the following raw materials in parts by weight: 188 portions of ciprofloxacin hydrochloride, 24-36 portions of microcrystalline cellulose, 12-23 portions of corn starch, 13-24 portions of crospovidone, 1.5-3.5 portions of magnesium stearate, 1.5-3.5 portions of superfine silica gel powder and 6-12 portions of film coating premix. The process of the medicine of the invention is stable, four dissolution curves dissolved out in vitro are consistent with those of the original researched reference preparation, the disintegration and absorption conditions of the medicine in vivo are guaranteed to be consistent with those of the original researched preparation, and the improvement of the product quality is facilitated.
Description
Technical Field
The invention belongs to the technical field of pharmacy, and particularly relates to ciprofloxacin hydrochloride tablets and a preparation method thereof.
Background
The product is quinolone antibiotic with wide antibacterial spectrum, and is suitable for urogenital system infection, respiratory tract infection, gastrointestinal tract infection, skin soft tissue infection, typhoid, etc. caused by sensitive bacteria. Gastrointestinal discomfort is a common adverse reaction, and the product was sold by Bayer with a 500mg tablet on the market in 1987 and is identified by FDA as a reference formulation, and the 100mg, 200mg tablets are Japanese reference formulations; the tablet is marketed in a plurality of member countries of European Union such as England, France, Italy and the like, 0.25g of the tablet is marketed in the first time in the year 1991, and the current domestic production batch of the tablet comprises two specifications of 0.25g and 0.5 g. The domestic manufacturers are numerous, but the quality is different, and the disintegration and the absorption difference with the original preparation in the body are larger.
Disclosure of Invention
In view of the above, the main object of the present invention is to provide ciprofloxacin hydrochloride tablets and a preparation method thereof.
In order to achieve the purpose, the technical scheme of the invention is realized as follows:
the ciprofloxacin hydrochloride tablet provided by the embodiment of the invention comprises the following raw materials in parts by weight: 188 portions of ciprofloxacin hydrochloride, 24-36 portions of microcrystalline cellulose, 12-23 portions of corn starch, 13-24 portions of crospovidone, 1.5-3.5 portions of magnesium stearate, 1.5-3.5 portions of superfine silica gel powder and 6-12 portions of film coating premix.
In the scheme, the composite material comprises the following raw materials in parts by weight: 300 parts of ciprofloxacin hydrochloride 250-containing material, 30-35 parts of microcrystalline cellulose, 15-20 parts of corn starch, 16-20 parts of crospovidone, 2-3 parts of magnesium stearate, 2-3 parts of superfine silica gel powder and 8-10 parts of film coating premix.
In the scheme, the composite material comprises the following raw materials in parts by weight: 291.15 parts of ciprofloxacin hydrochloride, 30.52 parts of microcrystalline cellulose, 22.26 parts of corn starch, 17.50 parts of crospovidone, 2.50 parts of magnesium stearate, 2.50 parts of superfine silica gel powder and 9.20 parts of film coating premix.
The embodiment of the invention also provides a preparation method of the cyprohexaxing hydrochloride tablet, which comprises the following steps:
step 1: weighing 50% of crospovidone with the prescription amount, weighing ciprofloxacin hydrochloride raw material with the prescription amount, and respectively sieving the raw material with a 50-mesh sieve to disperse lumps;
step 2: taking the sieved crospovidone and 50% of ciprofloxacin hydrochloride according to the prescription amount, mixing by using a 50-mesh oscillating screen according to an equivalent incremental method, continuously sieving the raw materials by using the 50-mesh oscillating screen for three times after all 50% of the raw materials are added, then adding the rest 50% of ciprofloxacin hydrochloride according to the prescription amount, and mixing by using a three-dimensional mixer to obtain a mixed material;
and step 3: granulating the mixed material by a dry granulating machine to obtain a material with the proportion of granules of 85-95%;
and 4, step 4: weighing microcrystalline cellulose, superfine silica gel powder, starch and the rest 50% of crospovidone according to the prescription amount, sieving by a 50-mesh sieve, granulating after sieving, adding a three-dimensional mixer for mixing, adding magnesium stearate according to the prescription amount after uniformly mixing, continuously mixing for 3min, and obtaining a total mixed material after mixing;
and 5: tabletting the total mixed material;
step 6: after tabletting, the tablets were coated with a coating solution to obtain ciprofloxacin hydrochloride tablets.
In the above scheme, the step 2 specifically comprises: and uniformly mixing the components by using a three-dimensional mixer until the RSD is less than or equal to 4.0 percent.
In the above scheme, the step 3 specifically comprises: controlling the no-load pressure of the dry type granulator to be 2mpa, the feeding speed to be 10-14rpm, the tabletting speed to be 20-37 rpm and the granulating speed to be 11-15 rpm, controlling the load pressure to be 2-3 mpa during granulating, granulating by adopting a stainless steel punching mesh with the diameter of 0.8mm, sieving the materials after one-time granulating by a sieve with 50 meshes, granulating the fine powder by the same step, sieving by the sieve with 50 meshes, granulating again, and circulating and granulating according to the steps, finally controlling the proportion of the particles in the materials to be 85-95%.
In the scheme, the bulk density of the total mixed material is 0.75g/cm3Tap density of 0.88g/cm3。
In the above scheme, the step 5 specifically comprises: the round shallow concave punching sheet with the diameter of 10mm is adopted, the weight difference is controlled to be +/-3% according to the weight of the intermediate body total mixed material converted by the weight of the sheet, and the hardness of the sheet is 90N-130N.
In the above scheme, the step 6 specifically includes: preparing coating liquid by purified water, wherein the solid content of the coating liquid is 14%, the coating weight gain is controlled to be 2.0-3.0%, and the coating parameters are as follows: the heating temperature is 49-52 ℃, the rotating speed of the coating pan is 7-8 rpm, the air supply temperature is 49-52 ℃, the air exhaust temperature is 42-43 ℃, and the rotating speed of the peristaltic pump is 11.0-12.0 rpm.
Compared with the prior art, the process of the medicine is stable, four dissolution curves of in vitro dissolution are consistent with those of the original researched reference preparation, the disintegration and absorption conditions of the medicine in vivo are guaranteed to be consistent with those of the original researched preparation, and the improvement of the product quality is facilitated.
Drawings
The accompanying drawings, which are included to provide a further understanding of the invention and are incorporated in and constitute a part of this specification, illustrate embodiment(s) of the invention and together with the description serve to explain the invention without limiting the invention. In the drawings:
FIG. 1 is a table comparing dissolution data of ciprofloxacin hydrochloride tablets prepared by the preparation method of ciprofloxacin hydrochloride tablets at pH 6.8;
FIG. 2 is a dissolution curve diagram of ciprofloxacin hydrochloride tablets prepared by the preparation method of ciprofloxacin hydrochloride tablets, wherein the dissolution curve diagram is pH 6.8;
FIG. 3 is a comparative table of dissolution data of ciprofloxacin hydrochloride tablets prepared by the method for preparing ciprofloxacin hydrochloride tablets, which is provided by the embodiment of the invention, at pH 1.2;
fig. 4 is a dissolution curve of the ciprofloxacin hydrochloride tablet prepared by the preparation method of the ciprofloxacin hydrochloride tablet at the ph of 1.2.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is described in further detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.
It should be noted that, in this document, the terms "comprises," "comprising," or any other variation thereof, are intended to cover a non-exclusive inclusion, such that a process, article, or apparatus that comprises a list of elements does not include only those elements but may include other elements not expressly listed or inherent to such process, article, or apparatus. Without further limitation, an element defined by the phrase "comprising an … …" does not exclude the presence of other like elements in a process, article, or apparatus that comprises the element.
The embodiment of the invention provides a ciprofloxacin hydrochloride tablet which comprises the following raw materials in parts by weight: 188 portions of ciprofloxacin hydrochloride, 24-36 portions of microcrystalline cellulose, 12-23 portions of corn starch, 13-24 portions of crospovidone, 1.5-3.5 portions of magnesium stearate, 1.5-3.5 portions of superfine silica gel powder and 6-12 portions of film coating premix.
Further, the feed additive comprises the following raw materials in parts by weight: 300 parts of ciprofloxacin hydrochloride 250-containing material, 30-35 parts of microcrystalline cellulose, 15-20 parts of corn starch, 16-20 parts of crospovidone, 2-3 parts of magnesium stearate, 2-3 parts of superfine silica gel powder and 8-10 parts of film coating premix.
Further, the feed additive comprises the following raw materials in parts by weight: 291.15 parts of ciprofloxacin hydrochloride, 30.52 parts of microcrystalline cellulose, 22.26 parts of corn starch, 17.50 parts of crospovidone, 2.50 parts of magnesium stearate, 2.50 parts of superfine silica gel powder and 9.20 parts of film coating premix.
The embodiment of the invention also provides a preparation method of the ciprofloxacin hydrochloride tablet, which comprises the following steps:
step 1: weighing 50% of crospovidone with the prescription amount, weighing ciprofloxacin hydrochloride raw material with the prescription amount, and respectively sieving the raw material with a 50-mesh sieve to disperse lumps;
step 2: taking the sieved crospovidone and 50% of ciprofloxacin hydrochloride according to the prescription amount, mixing by using a 50-mesh oscillating screen according to an equivalent incremental method, continuously sieving the raw materials by using the 50-mesh oscillating screen for three times after all 50% of the raw materials are added, then adding the rest 50% of ciprofloxacin hydrochloride according to the prescription amount, and mixing by using a three-dimensional mixer to obtain a mixed material;
specifically, a three-dimensional mixer is adopted for mixing uniformly until the RSD is less than or equal to 2.0 percent.
And step 3: granulating the mixed material by a dry granulating machine to obtain a material with the proportion of granules of 85-95%;
specifically, the no-load pressure of the dry type granulator is controlled to be 2mpa, the feeding speed is 10-14rpm, the tabletting speed is 20-37 rpm, the granulating speed is 11-15 rpm, the load pressure during granulating is controlled to be 2-3 mpa, a stainless steel punching mesh with the diameter of 0.8mm is adopted for granulating, the material after one-time granulating is sieved by a 50-mesh sieve, fine powder is granulated in the same step, and is sieved by the 50-mesh sieve and then granulated again, and the granulation is performed in a circulating manner, so that the proportion of particles in the material is controlled to be 85% -95%.
And 4, step 4: weighing microcrystalline cellulose, micro-powder silica gel, starch and the rest 50% of crospovidone in the prescription amount according to the prescription amount, sieving by a 50-mesh sieve, adding the sieved materials and the materials with the particle proportion of 85-95% into a three-dimensional mixer for mixing, adding magnesium stearate in the prescription amount after uniformly mixing, continuing mixing for 3min, and obtaining a total mixed material after mixing;
specifically, the bulk density of the total mixture is 0.75g/cm3Tap density of 0.88g/cm3。
And 5: tabletting the total mixed material;
specifically, a round shallow concave punching sheet with the diameter of 10mm is adopted, the weight of the sheet is converted according to the content of the total mixed material of the intermediate, the difference of the weight of the sheet is controlled to be +/-3%, and the hardness of the sheet is 90N-130N.
Step 6: after tabletting, the tablets were coated with a coating solution to obtain ciprofloxacin hydrochloride tablets.
Specifically, the coating solution is prepared by purified water, the solid content of the coating solution is 14%, the coating weight gain is controlled to be 2.0-3.0%, and the coating parameters are as follows: the heating temperature is 49-52 ℃, the rotating speed of the coating pan is 7-8 rpm, the air supply temperature is 49-52 ℃, the air exhaust temperature is 42-43 ℃, and the rotating speed of the peristaltic pump is 11.0-12.0 rpm.
Example 1
The embodiment 1 of the invention provides a preparation method of ciprofloxacin hydrochloride tablets, and the prepared ciprofloxacin hydrochloride tablets comprise the following raw materials in parts by weight: 188 parts of ciprofloxacin hydrochloride, 24 parts of microcrystalline cellulose, 12 parts of corn starch, 13 parts of crospovidone, 1.5 parts of magnesium stearate, 1.5 parts of superfine silica gel powder and 6 parts of film coating premix;
the preparation method comprises the following steps:
step 1: weighing 50% of crospovidone with the prescription amount, weighing ciprofloxacin hydrochloride raw material with the prescription amount, and respectively sieving the raw material with a 50-mesh sieve to disperse lumps;
step 2: taking the sieved crospovidone and 50% of ciprofloxacin hydrochloride according to the prescription amount, mixing by using a 50-mesh oscillating screen according to an equivalent incremental method, continuously sieving the raw materials by using the 50-mesh oscillating screen for three times after all 50% of the raw materials are added, then adding the rest 50% of ciprofloxacin hydrochloride according to the prescription amount, and mixing by using a three-dimensional mixer to obtain a mixed material;
specifically, a three-dimensional mixer is adopted for mixing uniformly until the RSD is less than or equal to 4.0 percent.
And step 3: granulating the mixed material by a dry granulating machine to obtain a material with the proportion of granules of 85-95%;
specifically, the no-load pressure of the dry granulating machine is controlled to be 2mpa, the feeding speed is 10rpm, the tabletting speed is 20rpm, the granulating speed is 11rpm, the load pressure during granulating is controlled to be 2mpa, stainless steel punching mesh with the diameter of 0.8mm is adopted for granulating, the material after one-time granulating is sieved by a 50-mesh sieve, the fine powder is granulated after the same step is continued, the material is sieved by the 50-mesh sieve and then granulated again, the granulating is carried out in a circulating manner, and finally the particle content in the material is controlled to be 85%.
And 4, step 4: weighing microcrystalline cellulose, superfine silica gel powder, starch and the rest 50% of crospovidone according to the prescription amount, sieving by a 50-mesh sieve, adding the sieved materials and the materials with the particle proportion of 85% into a three-dimensional mixer for mixing, adding the magnesium stearate according to the prescription amount after uniformly mixing, continuously mixing for 3min, and obtaining a total mixed material after mixing;
specifically, the bulk density of the total mixture is 0.75g/cm3Tap density of 0.88g/cm3。
And 5: tabletting the total mixed material;
specifically, a round shallow concave punching sheet with the diameter of 10mm is adopted, the weight of the sheet is converted according to the content of the total mixed material of the intermediate, the difference of the weight of the sheet is controlled to be +/-3%, and the hardness of the sheet is 90N.
Step 6: after tabletting, the tablets were coated with a coating solution to obtain ciprofloxacin hydrochloride tablets.
Specifically, the coating solution is prepared by purified water, the solid content of the coating solution is 14%, the coating weight gain is controlled to be 1.5%, and the coating parameters are as follows: the heating temperature is 49 ℃, the rotating speed of the coating pan is 7rpm, the air supply temperature is 49 ℃, the air exhaust temperature is 42 ℃, and the rotating speed of the peristaltic pump is 11.0 rpm.
Example 2
The embodiment 2 of the invention provides a preparation method of ciprofloxacin hydrochloride tablets, and the prepared ciprofloxacin hydrochloride tablets comprise the following raw materials in parts by weight: 235 parts of ciprofloxacin hydrochloride, 30 parts of microcrystalline cellulose, 18 parts of corn starch, 18 parts of crospovidone, 3 parts of magnesium stearate, 3 parts of superfine silica gel powder and 9 parts of film coating premix;
the preparation method comprises the following steps:
step 1: weighing 50% of crospovidone with the prescription amount, weighing ciprofloxacin hydrochloride raw material with the prescription amount, and respectively sieving the raw material with a 50-mesh sieve to disperse lumps;
step 2: taking the sieved crospovidone and 50% of ciprofloxacin hydrochloride according to the prescription amount, mixing by using a 50-mesh oscillating screen according to an equivalent incremental method, continuously sieving the raw materials by using the 50-mesh oscillating screen for three times after all 50% of the raw materials are added, then adding the rest 50% of ciprofloxacin hydrochloride according to the prescription amount, and mixing by using a three-dimensional mixer to obtain a mixed material;
specifically, a three-dimensional mixer is adopted for mixing uniformly until the RSD is less than or equal to 2.0 percent.
And step 3: granulating the mixed material by a dry granulator to obtain a material with the proportion of granules of 95%;
specifically, the no-load pressure of the dry granulating machine is controlled to be 2mpa, the feeding speed is 14rpm, the tabletting speed is 37rpm, the granulating speed is 15rpm, the load pressure during granulating is controlled to be 3mpa, stainless steel punching mesh with the diameter of 0.8mm is adopted for granulating, the material after one-time granulating is sieved by a 50-mesh sieve, the fine powder is granulated after the same step is continued, the material is sieved by the 50-mesh sieve again, the granulating is carried out in this way circularly, and finally the particle content in the material is controlled to be 95%.
And 4, step 4: weighing microcrystalline cellulose, superfine silica gel powder, starch and the rest 50% of crospovidone according to the prescription amount, sieving by a 50-mesh sieve, adding the sieved materials and the materials with the particle proportion of 95% into a three-dimensional mixer for mixing, adding the magnesium stearate according to the prescription amount after uniformly mixing, continuously mixing for 3min, and obtaining a total mixed material after mixing;
specifically, the bulk density of the total mixture is 0.75g/cm3Tap density of 0.88g/cm3。
And 5: tabletting the total mixed material;
specifically, a round shallow concave punching sheet with the diameter of 10mm is adopted, the weight of the sheet is converted according to the content of the total mixed material of the intermediate, the difference of the weight of the sheet is controlled to be +/-3%, and the hardness of the sheet is 120N.
Step 6: after tabletting, the tablets were coated with a coating solution to obtain ciprofloxacin hydrochloride tablets.
Specifically, the coating solution is prepared by purified water, the solid content of the coating solution is 14%, the coating weight gain is controlled to be 2.5%, and the coating parameters are as follows: the heating temperature is 52 ℃, the coating pan rotating speed is 8rpm, the air supply temperature is 52 ℃, the air exhaust temperature is 43 ℃, and the peristaltic pump rotating speed is 12.0 rpm.
Example 3
The embodiment 3 of the invention provides a preparation method of ciprofloxacin hydrochloride tablets, and the prepared ciprofloxacin hydrochloride tablets comprise the following raw materials in parts by weight: 375 parts of ciprofloxacin hydrochloride, 36 parts of microcrystalline cellulose, 23 parts of corn starch, 24 parts of crospovidone, 3.5 parts of magnesium stearate, 3.5 parts of superfine silica gel powder and 12 parts of film coating premix;
the preparation method comprises the following steps:
step 1: weighing 50% of crospovidone with the prescription amount, weighing ciprofloxacin hydrochloride raw material with the prescription amount, and respectively sieving the raw material with a 50-mesh sieve to disperse lumps;
step 2: taking the sieved crospovidone and 50% of ciprofloxacin hydrochloride according to the prescription amount, mixing by using a 50-mesh oscillating screen according to an equivalent incremental method, continuously sieving the raw materials by using the 50-mesh oscillating screen for three times after all 50% of the raw materials are added, then adding the rest 50% of ciprofloxacin hydrochloride according to the prescription amount, and mixing by using a three-dimensional mixer to obtain a mixed material;
specifically, a three-dimensional mixer is adopted for mixing uniformly until the RSD is less than or equal to 2.0 percent.
And step 3: granulating the mixed material by a dry granulating machine to obtain a material with 80% of granules;
specifically, the no-load pressure of the dry granulating machine is controlled to be 2mpa, the feeding speed is 12rpm, the tabletting speed is 29rpm, the granulating speed is 13rpm, the load pressure during granulating is controlled to be 2.5mpa, stainless steel punching mesh with the diameter of 0.8mm is adopted for granulating, the material after one-time granulating is sieved by a 50-mesh sieve, fine powder is granulated in the same step, the material is sieved by the 50-mesh sieve and then granulated again, and the granulation is carried out in a circulating manner, so that the proportion of particles in the material is controlled to be 90%.
And 4, step 4: weighing microcrystalline cellulose, superfine silica gel powder, starch and the rest 50% of crospovidone according to the prescription amount, sieving by a 50-mesh sieve, adding the sieved materials and 90% of granules into a three-dimensional mixer for mixing, adding magnesium stearate according to the prescription amount after mixing uniformly, continuing mixing for 3min, and obtaining a total mixed material after mixing;
specifically, the bulk density of the total mixture is 0.75g/cm3Tap density of 0.88g/cm3。
And 5: tabletting the total mixed material;
specifically, a round shallow concave punching sheet with the diameter of 10mm is adopted, the weight of the sheet is converted according to the content of the total mixed material of the intermediate, the difference of the weight of the sheet is controlled to be +/-3%, and the hardness of the sheet is 100N.
Step 6: after tabletting, the tablets were coated with a coating solution to obtain ciprofloxacin hydrochloride tablets.
Specifically, coating liquid is prepared by purified water, the solid content of the coating liquid is 14%, the weight gain of the coating is controlled to be 2%, and the coating parameters are as follows: the heating temperature is 51 ℃, the rotating speed of the coating pan is 7.5rpm, the air supply temperature is 502 ℃, the air exhaust temperature is 42.5 ℃, and the rotating speed of the peristaltic pump is 11.5 rpm.
Example 4
The embodiment 4 of the invention provides a preparation method of ciprofloxacin hydrochloride tablets, and the prepared ciprofloxacin hydrochloride tablets comprise the following raw materials in parts by weight: 250 parts of ciprofloxacin hydrochloride, 30 parts of microcrystalline cellulose, 15 parts of corn starch, 16 parts of crospovidone, 2 parts of magnesium stearate, 2 parts of superfine silica gel powder and 8 parts of film coating premix;
the preparation method comprises the following steps:
step 1: weighing 50% of crospovidone with the prescription amount, weighing ciprofloxacin hydrochloride raw material with the prescription amount, and respectively sieving the raw material with a 50-mesh sieve to disperse lumps;
step 2: taking the sieved crospovidone and 50% of ciprofloxacin hydrochloride according to the prescription amount, mixing by using a 50-mesh oscillating screen according to an equivalent incremental method, continuously sieving the raw materials by using the 50-mesh oscillating screen for three times after all 50% of the raw materials are added, then adding the rest 50% of ciprofloxacin hydrochloride according to the prescription amount, and mixing by using a three-dimensional mixer to obtain a mixed material;
specifically, a three-dimensional mixer is adopted for mixing uniformly until the RSD is less than or equal to 4.0 percent.
And step 3: granulating the mixed material by a dry granulating machine to obtain a material with the proportion of granules of 85-95%;
specifically, the no-load pressure of the dry granulating machine is controlled to be 2mpa, the feeding speed is 10rpm, the tabletting speed is 20rpm, the granulating speed is 11rpm, the load pressure during granulating is controlled to be 2mpa, stainless steel punching mesh with the diameter of 0.8mm is adopted for granulating, the material after one-time granulating is sieved by a 50-mesh sieve, the fine powder is granulated after the same step is continued, the material is sieved by the 50-mesh sieve and then granulated again, the granulating is carried out in a circulating manner, and finally the particle content in the material is controlled to be 85%.
And 4, step 4: weighing microcrystalline cellulose, superfine silica gel powder, starch and the rest 50% of crospovidone according to the prescription amount, sieving by a 50-mesh sieve, adding the sieved materials and the materials with the particle proportion of 85% into a three-dimensional mixer for mixing, adding the magnesium stearate according to the prescription amount after uniformly mixing, continuously mixing for 3min, and obtaining a total mixed material after mixing;
specifically, the bulk density of the total mixture is 0.75g/cm3Tap density of 0.88g/cm3。
And 5: tabletting the total mixed material;
specifically, a round shallow concave punching sheet with the diameter of 10mm is adopted, the weight of the sheet is converted according to the content of the total mixed material of the intermediate, the difference of the weight of the sheet is controlled to be +/-3%, and the hardness of the sheet is 90N.
Step 6: after tabletting, the tablets were coated with a coating solution to obtain ciprofloxacin hydrochloride tablets.
Specifically, the coating solution is prepared by purified water, the solid content of the coating solution is 14%, the coating weight gain is controlled to be 1.5%, and the coating parameters are as follows: heating temperature of 49 deg.C, coating pan rotation speed of 7rpm, air supply temperature of 49 deg.C, and air exhaust temperature of 42 deg.C
DEG C, and the rotation speed of a peristaltic pump is 11.0 rpm.
Example 5
The embodiment 5 of the invention provides a preparation method of ciprofloxacin hydrochloride tablets, and the prepared ciprofloxacin hydrochloride tablets comprise the following raw materials in parts by weight: 275 parts of ciprofloxacin hydrochloride, 32 parts of microcrystalline cellulose, 18 parts of corn starch, 18 parts of crospovidone, 2.5 parts of magnesium stearate, 2.5 parts of superfine silica gel powder and 9 parts of film coating premix;
the preparation method comprises the following steps:
step 1: weighing 50% of crospovidone with the prescription amount, weighing ciprofloxacin hydrochloride raw material with the prescription amount, and respectively sieving the raw material with a 50-mesh sieve to disperse lumps;
step 2: taking the sieved crospovidone and 50% of ciprofloxacin hydrochloride according to the prescription amount, mixing by using a 50-mesh oscillating screen according to an equivalent incremental method, continuously sieving the raw materials by using the 50-mesh oscillating screen for three times after all 50% of the raw materials are added, then adding the rest 50% of ciprofloxacin hydrochloride according to the prescription amount, and mixing by using a three-dimensional mixer to obtain a mixed material;
specifically, a three-dimensional mixer is adopted for mixing uniformly until the RSD is less than or equal to 4.0 percent.
And step 3: granulating the mixed material by a dry granulator to obtain a material with the proportion of granules of 95%;
specifically, the no-load pressure of the dry granulating machine is controlled to be 2mpa, the feeding speed is 14rpm, the tabletting speed is 37rpm, the granulating speed is 15rpm, the load pressure during granulating is controlled to be 3mpa, stainless steel punching mesh with the diameter of 0.8mm is adopted for granulating, the material after one-time granulating is sieved by a 50-mesh sieve, the fine powder is granulated after the same step is continued, the material is sieved by the 50-mesh sieve again, the granulating is carried out in this way circularly, and finally the particle content in the material is controlled to be 95%.
And 4, step 4: weighing microcrystalline cellulose, superfine silica gel powder, starch and the rest 50% of crospovidone according to the prescription amount, sieving by a 50-mesh sieve, adding the sieved materials and the materials with the particle proportion of 95% into a three-dimensional mixer for mixing, adding the magnesium stearate according to the prescription amount after uniformly mixing, continuously mixing for 3min, and obtaining a total mixed material after mixing;
specifically, the bulk density of the total mixture is 0.75g/cm3Tap density of 0.88g/cm3。
And 5: tabletting the total mixed material;
specifically, a round shallow concave punching sheet with the diameter of 10mm is adopted, the weight of the sheet is converted according to the content of the total mixed material of the intermediate, the difference of the weight of the sheet is controlled to be +/-3%, and the hardness of the sheet is 130N.
Step 6: after tabletting, the tablets were coated with a coating solution to obtain ciprofloxacin hydrochloride tablets.
Specifically, the coating solution is prepared by purified water, the solid content of the coating solution is 14%, the coating weight gain is controlled to be 2.5%, and the coating parameters are as follows: the heating temperature is 52 ℃, the coating pan rotating speed is 8rpm, the air supply temperature is 52 ℃, the air exhaust temperature is 43 ℃, and the peristaltic pump rotating speed is 12.0 rpm.
Example 6
The embodiment 6 of the invention provides a preparation method of ciprofloxacin hydrochloride tablets, and the prepared ciprofloxacin hydrochloride tablets comprise the following raw materials in parts by weight: 300 parts of ciprofloxacin hydrochloride, 35 parts of microcrystalline cellulose, 20 parts of corn starch, 20 parts of crospovidone, 3 parts of magnesium stearate, 3 parts of superfine silica gel powder and 10 parts of film coating premix;
the preparation method comprises the following steps:
step 1: weighing 50% of crospovidone with the prescription amount, weighing ciprofloxacin hydrochloride raw material with the prescription amount, and respectively sieving the raw material with a 50-mesh sieve to disperse lumps;
step 2: taking the sieved crospovidone and 50% of ciprofloxacin hydrochloride according to the prescription amount, mixing by using a 50-mesh oscillating screen according to an equivalent incremental method, continuously sieving the raw materials by using the 50-mesh oscillating screen for three times after all 50% of the raw materials are added, then adding the rest 50% of ciprofloxacin hydrochloride according to the prescription amount, and mixing by using a three-dimensional mixer to obtain a mixed material;
specifically, a three-dimensional mixer is adopted for mixing uniformly until the RSD is less than or equal to 4.0 percent.
And step 3: granulating the mixed material by a dry granulating machine to obtain a material with 80% of granules;
specifically, the no-load pressure of the dry granulating machine is controlled to be 2mpa, the feeding speed is 12rpm, the tabletting speed is 29rpm, the granulating speed is 13rpm, the load pressure during granulating is controlled to be 2.5mpa, stainless steel punching mesh with the diameter of 0.8mm is adopted for granulating, the material after one-time granulating is sieved by a 50-mesh sieve, fine powder is granulated in the same step, the material is sieved by the 50-mesh sieve and then granulated again, and the granulation is carried out in a circulating manner, so that the proportion of particles in the material is controlled to be 90%.
And 4, step 4: weighing microcrystalline cellulose, superfine silica gel powder, starch and the rest 50% of crospovidone according to the prescription amount, sieving by a 50-mesh sieve, adding the sieved materials and 90% of granules into a three-dimensional mixer for mixing, adding magnesium stearate according to the prescription amount after mixing uniformly, continuing mixing for 3min, and obtaining a total mixed material after mixing;
specifically, the bulk density of the total mixture is 0.75g/cm3Tap density of 0.88g/cm3。
And 5: tabletting the total mixed material;
specifically, a round shallow concave punching sheet with the diameter of 10mm is adopted, the weight of the sheet is converted according to the content of the total mixed material of the intermediate, the difference of the weight of the sheet is controlled to be +/-3%, and the hardness of the sheet is 100N.
Step 6: after tabletting, the tablets were coated with a coating solution to obtain ciprofloxacin hydrochloride tablets.
Specifically, coating liquid is prepared by purified water, the solid content of the coating liquid is 14%, the weight gain of the coating is controlled to be 2%, and the coating parameters are as follows: the heating temperature is 51 ℃, the rotating speed of the coating pan is 7.5rpm, the air supply temperature is 502 ℃, the air exhaust temperature is 42.5 ℃, and the rotating speed of the peristaltic pump is 11.5 rpm.
Example 7
The embodiment 7 of the invention provides a preparation method of ciprofloxacin hydrochloride tablets, and the prepared ciprofloxacin hydrochloride tablets comprise the following raw materials in parts by weight: 291.15 parts of ciprofloxacin hydrochloride, 34.52 parts of microcrystalline cellulose, 17.26 parts of corn starch, 18.50 parts of crospovidone, 2.50 parts of magnesium stearate, 2.50 parts of superfine silica gel powder and 9.20 parts of film coating premix;
the preparation method comprises the following steps:
step 1: weighing 50% of crospovidone with the prescription amount, weighing ciprofloxacin hydrochloride raw material with the prescription amount, and respectively sieving the raw material with a 50-mesh sieve to disperse lumps;
step 2: taking the sieved crospovidone and 50% of ciprofloxacin hydrochloride according to the prescription amount, mixing by using a 50-mesh oscillating screen according to an equivalent incremental method, continuously sieving the raw materials by using the 50-mesh oscillating screen for three times after all 50% of the raw materials are added, then adding the rest 50% of ciprofloxacin hydrochloride according to the prescription amount, and mixing by using a three-dimensional mixer to obtain a mixed material;
specifically, a three-dimensional mixer is adopted for mixing uniformly until the RSD is less than or equal to 4.0 percent.
And step 3: granulating the mixed material by a dry granulator to obtain a material with the proportion of granules of 95%;
specifically, the no-load pressure of the dry granulating machine is controlled to be 2mpa, the feeding speed is 14rpm, the tabletting speed is 37rpm, the granulating speed is 15rpm, the load pressure during granulating is controlled to be 3mpa, stainless steel punching mesh with the diameter of 0.8mm is adopted for granulating, the material after one-time granulating is sieved by a 50-mesh sieve, the fine powder is granulated after the same step is continued, the material is sieved by the 50-mesh sieve again, the granulating is carried out in this way circularly, and finally the particle content in the material is controlled to be 95%.
And 4, step 4: weighing microcrystalline cellulose, superfine silica gel powder, starch and the rest 50% of crospovidone according to the prescription amount, sieving by a 50-mesh sieve, adding the sieved materials and the materials with the particle proportion of 95% into a three-dimensional mixer for mixing, adding the magnesium stearate according to the prescription amount after uniformly mixing, continuously mixing for 3min, and obtaining a total mixed material after mixing;
specifically, the bulk density of the total mixture is 0.75g/cm3Tap density of 0.88g/cm3。
And 5: tabletting the total mixed material;
specifically, a round shallow concave punching sheet with the diameter of 10mm is adopted, the weight of the sheet is converted according to the content of the total mixed material of the intermediate, the difference of the weight of the sheet is controlled to be +/-3%, and the hardness of the sheet is 120N.
Step 6: after tabletting, the tablets were coated with a coating solution to obtain ciprofloxacin hydrochloride tablets.
Specifically, the coating solution is prepared by purified water, the solid content of the coating solution is 14%, the coating weight gain is controlled to be 2.5%, and the coating parameters are as follows: the heating temperature is 52 ℃, the coating pan rotating speed is 8rpm, the air supply temperature is 52 ℃, the air exhaust temperature is 43 ℃, and the peristaltic pump rotating speed is 12.0 rpm.
As shown in fig. 1 and 2, the average cumulative dissolution amount of the preparation at each time point is more than 50%.
As shown in fig. 3 and 4, the average cumulative elution amount of the preparation in 15 minutes was ≧ 85%.
The above description is only a preferred embodiment of the present invention, and is not intended to limit the scope of the present invention.
Claims (9)
1. The ciprofloxacin hydrochloride tablet is characterized by comprising the following raw materials in parts by weight: 188 portions of ciprofloxacin hydrochloride, 24-36 portions of microcrystalline cellulose, 12-23 portions of corn starch, 13-24 portions of crospovidone, 1.5-3.5 portions of magnesium stearate, 1.5-3.5 portions of superfine silica gel powder and 6-12 portions of film coating premix.
2. The ciprofloxacin hydrochloride tablet according to claim 1, which is prepared from the following raw materials in parts by weight: 300 parts of ciprofloxacin hydrochloride 250-containing material, 30-35 parts of microcrystalline cellulose, 15-20 parts of corn starch, 16-20 parts of crospovidone, 2-3 parts of magnesium stearate, 2-3 parts of superfine silica gel powder and 8-10 parts of film coating premix.
3. The ciprofloxacin hydrochloride tablet according to claim 2, which is prepared from the following raw materials in parts by weight: 291.15 parts of ciprofloxacin hydrochloride, 30.52 parts of microcrystalline cellulose, 22.26 parts of corn starch, 17.50 parts of crospovidone, 2.50 parts of magnesium stearate, 2.50 parts of superfine silica gel powder and 9.20 parts of film coating premix.
4. A method of preparing the ciprofloxacin hydrochloride tablet of any one of claims 1-3, comprising:
step 1: weighing 50% of crospovidone with the prescription amount, weighing ciprofloxacin hydrochloride raw material with the prescription amount, and respectively sieving the raw material with a 50-mesh sieve to disperse lumps;
step 2: taking the sieved crospovidone and 50% of ciprofloxacin hydrochloride according to the prescription amount, mixing by using a 50-mesh oscillating screen according to an equivalent incremental method, continuously sieving the raw materials by using the 50-mesh oscillating screen for three times after all 50% of the raw materials are added, then adding the rest 50% of ciprofloxacin hydrochloride according to the prescription amount, and mixing by using a three-dimensional mixer to obtain a mixed material;
and step 3: granulating the mixed material by a dry granulating machine to obtain a material with the proportion of granules of 85-95%;
and 4, step 4: weighing microcrystalline cellulose, superfine silica gel powder, starch and the rest 50% of crospovidone according to the prescription amount, sieving by a 50-mesh sieve, granulating after sieving, adding a three-dimensional mixer for mixing, adding magnesium stearate according to the prescription amount after uniformly mixing, continuously mixing for 3min, and obtaining a total mixed material after mixing;
and 5: tabletting the total mixed material;
step 6: after tabletting, the tablets were coated with a coating solution to obtain ciprofloxacin hydrochloride tablets.
5. The method for preparing the ciprofloxacin hydrochloride tablet according to claim 4, wherein the step 2 specifically comprises the following steps: and uniformly mixing the components by using a three-dimensional mixer until the RSD is less than or equal to 4.0 percent.
6. The preparation method of the ciprofloxacin hydrochloride tablet according to claim 4 or 5, wherein the step 3 specifically comprises the following steps: controlling the no-load pressure of the dry type granulator to be 2mpa, the feeding speed to be 10-14rpm, the tabletting speed to be 20-37 rpm and the granulating speed to be 11-15 rpm, controlling the load pressure to be 2-3 mpa during granulating, granulating by adopting a stainless steel punching mesh with the diameter of 0.8mm, sieving the materials after one-time granulating by a sieve with 50 meshes, granulating the fine powder by the same step, sieving by the sieve with 50 meshes, granulating again, and circulating and granulating according to the steps, finally controlling the proportion of the particles in the materials to be 85-95%.
7. The method of preparing ciprofloxacin hydrochloride tablets of claim 6, wherein the bulk density of the total mixture is 0.75g/cm3Tap density of 0.88g/cm3。
8. The method for preparing the ciprofloxacin hydrochloride tablet according to claim 6, wherein the step 5 specifically comprises the following steps: the round shallow concave punching sheet with the diameter of 10mm is adopted, the weight difference is controlled to be +/-3% according to the weight of the intermediate body total mixed material converted by the weight of the sheet, and the hardness of the sheet is 90N-130N.
9. The method for preparing the ciprofloxacin hydrochloride tablet according to claim 7, wherein the step 6 specifically comprises the following steps: preparing coating liquid by purified water, wherein the solid content of the coating liquid is 14%, the coating weight gain is controlled to be 2.0-3.0%, and the coating parameters are as follows: the heating temperature is 49-52 ℃, the rotating speed of the coating pan is 7-8 rpm, the air supply temperature is 49-52 ℃, the air exhaust temperature is 42-43 ℃, and the rotating speed of the peristaltic pump is 11.0-12.0 rpm.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN1084188C (en) * | 1986-01-21 | 2002-05-08 | 拜尔公司 | Pharmaceutical formulations of ciprofloxacin |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1084188C (en) * | 1986-01-21 | 2002-05-08 | 拜尔公司 | Pharmaceutical formulations of ciprofloxacin |
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