CN113318081A - Ibuprofen granule and preparation method thereof - Google Patents
Ibuprofen granule and preparation method thereof Download PDFInfo
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- CN113318081A CN113318081A CN202110579189.4A CN202110579189A CN113318081A CN 113318081 A CN113318081 A CN 113318081A CN 202110579189 A CN202110579189 A CN 202110579189A CN 113318081 A CN113318081 A CN 113318081A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1617—Organic compounds, e.g. phospholipids, fats
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- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1617—Organic compounds, e.g. phospholipids, fats
- A61K9/1623—Sugars or sugar alcohols, e.g. lactose; Derivatives thereof; Homeopathic globules
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- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin
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- A—HUMAN NECESSITIES
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- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1682—Processes
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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Abstract
The application provides ibuprofen particles and a preparation method thereof, wherein the method comprises the following steps: crushing the raw material medicines: the ibuprofen raw material medicine is crushed to specified fineness to obtain a first raw material medicine. Raw and auxiliary material sieving: and sieving the adhesive, the first raw material medicine and the filler to obtain the raw and auxiliary materials with preset meshes. Preparing a mixed solution: the flavoring agent and correctant are dissolved in purified water according to the prescription. Mixing: adding the raw and auxiliary materials with preset meshes and the disintegrating agent into a mixing machine, mixing the raw and auxiliary materials and the disintegrating agent into dry powder, and adding the mixed solution for wet mixing to obtain a soft material. A granulation step: and extruding the soft material through a granulator to obtain wet granules. And (3) drying: the wet granulation is dried to obtain dry granulation. Finishing the grains: and removing large particles and fine powder in the dry particles to obtain the target ibuprofen particles. The application improves the combination degree of the raw material medicines, the raw and auxiliary materials and the adhesive, and further improves the uniformity and the dissolution performance of the medicine.
Description
Technical Field
The invention belongs to the field of medicines, and particularly relates to ibuprofen granules and a preparation method thereof.
Background
Ibuprofen is a non-steroidal anti-inflammatory drug, mainly inhibits the synthesis of cyclooxygenase and prostaglandin to achieve the effects of resisting inflammation and easing pain, plays a role in defervescing through hypothalamic body temperature regulation center, has a large popularization effect and a large popularization and application effect. Clinically, the traditional Chinese medicine composition is generally suitable for relieving various diseases such as rheumatoid arthritis, osteoarthritis, spondyloarthropathy, gouty arthritis, rheumatic arthritis and the like.
The currently common ibuprofen preparation method comprises the steps of preparing a quick-release part, namely mixing ibuprofen, a disintegrating agent and an adhesive, performing wet granulation and drying to obtain quick-release granules; preparing a sustained-release part, namely extruding ibuprofen, a corrosion inhibitor, a disintegrating agent and an adhesive into particles by a rounding method, coating to obtain the sustained-release part, and finally pressing the quick-release part and the sustained-release part to obtain the ibuprofen.
The ibuprofen medicament components prepared by the method provided by the related technology are easy to separate due to the difference of particle density, and have poor solubility.
Disclosure of Invention
In order to solve the technical problems that the ibuprofen medicament components prepared by the method provided by the related technology are easy to separate due to the difference of particle density and have poor solubility, the invention provides ibuprofen particles and a preparation method thereof.
The specific technical scheme of the invention is as follows:
the invention provides ibuprofen particles, which comprise:
0.8 to 1.2 portions of ibuprofen, 3.0 to 4.0 portions of filling agent, 0.10 to 2 portions of adhesive and disintegrating agent, and 0.001 to 0.002 portion of flavoring agent and flavoring agent.
In an alternative embodiment, the ibuprofen particles comprise: 1 part by weight of ibuprofen, 3.7 parts by weight of filler, 0.15 part by weight of adhesive and disintegrant and 0.001 part by weight of flavoring agent and flavoring agent.
In an alternative embodiment, the filler is lactose, the binder is hydroxypropylcellulose, the disintegrant is croscarmellose sodium, the flavoring agent is fumaric acid, and the flavoring agent is sodium saccharin.
On the other hand, the embodiment of the application also provides a preparation method of ibuprofen particles, and the preparation method of the ibuprofen particles comprises the following steps:
crushing the raw material medicines: crushing the ibuprofen raw material drug to preset fineness to obtain a first raw material drug;
raw and auxiliary material sieving: sieving the adhesive, the first raw material medicine and the filler to obtain raw and auxiliary materials with preset meshes;
mixing: adding the raw and auxiliary materials with preset meshes and the disintegrating agent into a mixing machine, mixing the raw and auxiliary materials with the preset meshes and the disintegrating agent into dry powder, and adding the mixed solution for wet mixing to obtain a soft material;
a granulation step: extruding the soft material through a granulator to obtain wet granules;
and (3) drying: drying the wet granules to obtain dry granules;
finishing the grains: and removing large particles and fine powder in the dry particles to obtain the target ibuprofen particles.
In an optional embodiment, the bulk drug pulverizing step comprises: and adding the ibuprofen raw material at a constant speed by a grinder under preset current and preset frequency at preset feeding frequency, and grinding to preset fineness.
In an alternative embodiment, the preset fineness is 2 μm ≦ D50 ≦ 18 μm, and 4 μm ≦ D90 ≦ 56 μm.
In an optional embodiment, the preset mesh number is 20 meshes.
In an optional embodiment, the method further comprises the step of preparing a mixture: mixing fumaric acid, a flavoring agent and purified water according to a ratio of 1:1:1200 to obtain the mixed solution.
In an optional embodiment, the method further comprises an ingredient mixing step: adding the raw and auxiliary materials with the preset mesh number and the disintegrating agent into a mixer for dry mixing; adding the mixed solution, and wet mixing to obtain a soft material.
In an alternative embodiment, the method further comprises a granulation step: and extruding the soft material through a granulator to obtain wet granules.
In an alternative embodiment, the method further comprises a drying step: drying the wet granules to obtain wet granules.
In an alternative embodiment, the method further comprises a step of straightening granules: and removing large particles and fine powder in the dry particles to obtain the target ibuprofen particles.
In an optional embodiment, the method further comprises a total mixing step: adding the target ibuprofen particles into a mixer for integral mixing;
preferably, the method further comprises an intermediate detection step: and sampling and detecting the target ibuprofen particles according to a sampling rule, and taking the ibuprofen particles meeting the detection standard as the target ibuprofen particles.
The invention has the following beneficial effects:
the ibuprofen granule provided by the embodiment of the application is compounded by the components in a synergistic manner, so that the prepared ibuprofen granule has the same bioequivalence and quality consistency as the original grinding medicine, and the preparation process is simple and reliable.
Drawings
Fig. 1 is a schematic flow chart of a method for preparing ibuprofen granules provided in the embodiments of the present application.
Detailed Description
The present invention will be described in further detail with reference to the following examples and drawings.
The embodiment of the application provides an ibuprofen granule, this ibuprofen granule includes: 0.8 to 1.2 portions of ibuprofen, 3.0 to 4.0 portions of filling agent, 0.10 to 2 portions of adhesive and disintegrating agent, and 0.001 to 0.002 portion of flavoring agent and flavoring agent.
The ibuprofen granule provided by the embodiment of the application is compounded by the components in a synergistic manner, so that the prepared ibuprofen granule has the same bioequivalence and quality consistency as the original grinding medicine, and the preparation process is simple and reliable.
The ibuprofen granules provided in the examples of the present application will be further explained and described below by means of optional examples.
In an alternative embodiment, the ibuprofen may be 0.8, 0.9, 1, 1.1, 1.2, etc., filler 3, 3.1, 3.2, 3.3, 3.4, 3.5, 3.6, 3.7, 3.8, 3.9, or 4, etc., binder and disintegrant may be 0.1, 0.11, 0.12, 0.13, 0.14, 0.15, 0.16, 0.17, 0.18, 0.19, or 2, etc., flavoring and flavoring agents may be 0.001, or 0.002, etc.
In an alternative embodiment, the ibuprofen particles comprise: 1 part by weight of ibuprofen, 3.7 parts by weight of filler, 0.15 part by weight of adhesive and disintegrant and 0.001 part by weight of flavoring agent and flavoring agent.
In an alternative embodiment, the filler is lactose, the binder is hydroxypropylcellulose, and the disintegrant is croscarmellose sodium, wherein the flavoring agent is fumaric acid and the flavoring agent is sodium saccharin.
On the other hand, the embodiment of the application also provides a preparation method of ibuprofen particles, and the preparation method of the ibuprofen particles comprises the following steps:
s101, crushing the raw material medicines: the ibuprofen raw material medicine is crushed to a preset fineness to obtain a first raw material medicine.
S102, raw and auxiliary material sieving step: and sieving the adhesive, the first raw material medicine and the filler to obtain the raw and auxiliary materials with preset meshes.
S103, a mixing step: adding the first raw material medicine, the adhesive with a preset mesh number, the filling agent and the disintegrating agent into a mixing machine, mixing the mixture with dry powder, and adding the mixed solution for wet mixing to obtain a soft material.
S104, granulating: and extruding the soft material through a granulator to obtain wet granules.
S105, a drying step: the wet granulation is dried to obtain dry granulation.
S106, size stabilization step: and removing large particles and fine powder in the dry particles to obtain the target ibuprofen particles.
According to the method provided by the embodiment of the application, the ibuprofen raw material medicine is crushed to the preset fineness through the raw material medicine crushing step, the fineness of the particles in the raw material medicine powder is crushed to be the same or similar, the particle density difference among the particles of the ibuprofen raw material medicine is reduced, and the segregation phenomenon is avoided when the ibuprofen raw material medicine is mixed with the raw and auxiliary materials; the adhesive, the first raw material medicine and the filler are sieved through the raw and auxiliary material sieving step, so that the mesh number of the adhesive, the first raw material medicine and the filler is kept consistent, the particle spacing between the raw material medicines and the raw and auxiliary materials, the particle spacing between the raw and auxiliary materials and the particle spacing between the raw and auxiliary materials are reduced, the combination degree between the raw material medicines and the raw and auxiliary materials and the adhesive is improved, and meanwhile, the flavoring agent and the flavoring agent are dissolved in purified water to serve as a wetting agent, so that the uniformity and the dissolution performance of the medicine are improved.
The preparation processes provided in the examples of the present application will be further explained and described below by means of optional examples.
S101, crushing the raw material medicines: the ibuprofen raw material medicine is crushed to a preset fineness to obtain a first raw material medicine.
The bulk drug can be crushed by the airflow crusher in the bulk drug crushing step provided by the embodiment of the application.
In an optional embodiment, the bulk drug pulverizing step comprises: adding ibuprofen raw material at a constant speed at a preset feeding frequency under a preset current and a preset frequency through a pulverizer, and pulverizing to a preset fineness. As an example, the current of a grading motor of the airflow type grinder can be set to be 2A, the frequency of a grading wheel is set to be 80Hz, the feeding frequency is set to be 20Hz, and the ibuprofen raw material medicine is ground by uniformly feeding the material.
In an alternative embodiment, the predetermined fineness is 2 μm D50 ≦ 18 μm, 4 μm D90 ≦ 56 μm.
It should be noted that D50 refers to the particle size corresponding to the cumulative percentage of particle size distribution of a sample reaching 50%. Its physical meaning is that the particle size is greater than 50% of its particles and less than 50% of its particles, D50 also being referred to as the median or median particle size. D90 refers to the particle size corresponding to 90% of the cumulative percent particle size distribution for a sample. Its physical meaning is that the particles having a particle size of less than 90% of its particles and more than 10% of its particles.
S102, raw and auxiliary material sieving step: and sieving the adhesive, the first raw material medicine and the filler to obtain the raw and auxiliary materials with preset meshes.
In an alternative embodiment, the predetermined mesh count is 20 mesh.
In an alternative embodiment, the adhesive and the first drug substance may be sieved by a hand sieve with a mesh size of 20 mesh, and the filler may be sieved by a rocking granulator with a mesh size of 20 mesh.
In an optional embodiment, the method further comprises the step of compounding: adding the first raw material medicine, adhesive with preset mesh number, filler and disintegrating agent into a mixer for dry powder mixing.
In an optional embodiment, the method further comprises the step of formulating a cocktail: and mixing the flavoring agent, the flavoring agent and the purified water according to the proportion of 1:1:1200 to obtain a mixed solution.
In an alternative embodiment, the flavoring agent is fumaric acid and the flavoring agent is sodium saccharin.
Further, fumaric acid, saccharin sodium and purified water are prepared into a solution according to the ratio of 1:1:1200 for later use. It should be noted that, a small amount of warm water of 40 ℃ to 50 ℃ can be used for dissolving the fumaric acid and the saccharin sodium before preparing the mixed solution, so as to improve the dissolving rate and the mixing uniformity of the fumaric acid and the saccharin sodium.
S103, a mixing step: adding the raw and auxiliary materials with preset meshes and the disintegrating agent into a mixing machine, mixing the raw and auxiliary materials and the disintegrating agent into dry powder, and adding the mixed solution for wet mixing to obtain a soft material.
Further, ibuprofen, lactose, hydroxypropyl cellulose and croscarmellose sodium were added to a mixer, and the dry powders were mixed for 40 minutes. Adding mixed solution of fumaric acid and saccharin sodium, wet mixing for about 5 min, and making into soft material which can be kneaded into mass by hand, and lightly pressing to disperse, and has uniform moistening and uniform color.
S104, granulating: and extruding the soft material through a granulator to obtain wet granules.
Adding the prepared soft material into a rotary granulator for rotary extrusion, and timely checking whether the extrudate is normal. Setting the air speed of the spherical shot blasting machine to be 20 Hz-50 Hz and the rotating speed of the rotary table to be 10 Hz-30 Hz, adding 10-30 kg of extrudate, observing the fluidization state of the material at any time, and keeping the material in a good fluidization state in the rotary granulator; and discharging after shot blasting operation is finished, transferring the discharged wet particles into a hopper of the efficient boiling dryer, and starting a drying step after the last discharged material is transferred.
S105, a drying step: the wet granulation is dried to obtain dry granulation.
Putting the rounded wet particles into a hopper of a high-efficiency boiling dryer, setting the air inlet temperature of air for drying to be 60 ℃, the air speed to be 30 Hz-50 Hz and the steam pressure to be 0.2 Mpa-0.4 Mpa, recording the air inlet temperature, the air outlet temperature and the material temperature every 5 minutes, drying the materials for 5 minutes after the material temperature reaches more than 50 ℃, closing the steam, and discharging the materials after the material temperature is lower than 40 ℃ and the drying weight loss is required to be not more than 1.5%.
S106, size stabilization step: and removing large particles and fine powder in the dry particles to obtain the target ibuprofen particles.
After drying, the dry particles are sieved by a ternary spin-vibration sieve of 16/60 meshes, and large particles and fine powder are removed. And (4) filling the qualified granules after finishing the granules into a clean low-density polyethylene bag, tightly binding, and waiting for total mixing.
In an optional embodiment, the method further comprises a total mixing step: the target ibuprofen particles were added to the mixer for bulk mixing.
And adding the target ibuprofen particles into a three-dimensional motion mixer, and mixing for 10 minutes at the rotating speed of 8 revolutions per minute. And (3) putting the mixed particles into a clean double-layer low-density polyethylene bag, tightly binding, conveying into an intermediate station (the temperature is 18-26 ℃, the humidity is less than or equal to 65%, and the storage time of the intermediate particles is 28 days), and waiting for detection.
In an optional embodiment, the method further comprises an intermediate detection step: and sampling and detecting the target ibuprofen particles according to a sampling rule, and taking the ibuprofen particles meeting the detection standard as the target ibuprofen particles.
Sampling and inspecting according to a sampling procedure, wherein the ibuprofen particles provided by the embodiment of the application are white particles; the content of 6 points has a relative standard deviation RSD not more than 2.0%; ibuprofen as provided in the examples of the present application (according to C)13H18O2Calculated) should be 19.0% to 21.0%; the drying weight loss is not more than 1.5%; the intermediate granularity is measured by a double-screening method, and the sum of the intermediate granularity which can not pass through a No. 1 screen and the intermediate granularity which can pass through a No. 5 screen is not more than 15 percent of the test quantity; the dissolution rate (dissolution rate: the dissolution rate and degree of the active drug from common preparations such as tablets, capsules or granules and the like under specified conditions) of the granules is more than or equal to 85 percent of the marked amount within 15 minutes.
In an optional embodiment, the method further comprises racking: setting transverse sealing temperature (100-170 ℃), longitudinal sealing temperature (130-220 ℃) and compressed air range of 0.45-0.8 Mpa, filling qualified granules into a hopper of a racking machine, adjusting filling amount (1 g/bag, filling amount difference +/-9%) and operating speed of 180-220 bags/minute. And adjusting the batch number at the position of the rolling port, and starting a machine to pack the particles into the plastic film. Checking the loading amount every 60 minutes, and requiring tight sealing, no air leakage, clear and correct batch number. And executing according to the standard operating specification of the external packaging process.
The preparation process and the prepared ibuprofen granules provided in the examples of the present application will be further described by specific examples below.
Examples
(1) Crushing the raw material medicines: setting the current of a grading motor of the airflow type grinder to be 2A, the frequency of a grading wheel to be 80Hz and the feeding frequency to be 20Hz, adding the ibuprofen raw material medicine at a constant speed, grinding the ibuprofen raw material medicine, and enabling the ground ibuprofen raw material medicine to reach a preset fineness (the particle size detection report of the ibuprofen raw material medicine is that the fineness is 2 mu m or more and D50 or more and 18 mu m or less and that the fineness is 4 mu m or more and D90 or more and 56 mu m or less).
(2) Sieving raw materials and auxiliary materials: the hydroxypropyl cellulose and the crushed ibuprofen raw material are screened by a manual screen with the mesh number of 20 meshes; the lactose is sieved by a swing granulator, and the mesh number of the screen is 20 meshes.
(3) Preparing materials: before batching, the names, the numbers and the weights of the raw materials and the auxiliary materials are checked, and the raw materials and the auxiliary materials are placed in a double-layer low-density polyethylene bag according to batch feeding quantity.
(4) Preparing a mixed solution of fumaric acid and sodium saccharin: fumaric acid, saccharin sodium and purified water are prepared into solution according to the proportion of 1:1:1200 for later use (the fumaric acid and the saccharin sodium are dissolved by a small amount of warm water with the temperature of 40-50 ℃).
(5) Mixing: lactose, ibuprofen, hydroxypropyl cellulose and croscarmellose sodium are added into a mixer, and the dry powder is mixed for 40 minutes. Adding mixed solution of fumaric acid and saccharin sodium, wet mixing for about 5 min, and making into soft material which can be kneaded into mass by hand, and lightly pressing to disperse, and has uniform moistening and uniform color.
(6) And (3) granulating: adding the prepared soft material into a rotary granulator for rotary extrusion, and timely checking whether the extrudate is normal. Setting the air speed of the spherical shot blasting machine to be 20 Hz-50 Hz and the rotating speed of the rotary table to be 10 Hz-30 Hz, adding 10-30 kg of extrudate, observing the fluidization state of the material at any time, and keeping the material in a good fluidization state in the container under the condition of pelleting; and discharging after shot blasting operation is finished, transferring the discharged wet particles into a hopper of the efficient boiling dryer, and starting a drying step after the last discharged material is transferred.
(7) And (3) drying: putting the rounded wet particles into a hopper of a high-efficiency boiling dryer, setting the air inlet temperature of air for drying to be 60 ℃, the air speed to be 30 Hz-50 Hz and the steam pressure to be 0.2 Mpa-0.4 Mpa, recording the air inlet temperature, the air outlet temperature and the material temperature every 5 minutes, drying the materials for 5 minutes after the material temperature reaches more than 50 ℃, closing the steam, and discharging the materials after the material temperature is lower than 40 ℃ and the drying weight loss is required to be not more than 1.5%.
(8) Straightening: after drying, the granules are sieved by a ternary spin-vibration sieve of 16/60 meshes, and large granules and fine powder are removed. And (4) filling the qualified granules after finishing the granules into a clean low-density polyethylene bag, tightly binding, and waiting for total mixing.
(9) Total mixing: the particles are added into a three-dimensional motion mixer, the rotating speed is 8 r/min, and the mixture is mixed for 10 minutes. And (3) filling the mixed particles into a clean double-layer low-density polyethylene bag, tightly binding, conveying into an intermediate station (the temperature is 18-26 ℃, the humidity is less than or equal to 65%, and the storage time of the intermediate particles is 28 days), and inspecting.
(10) And (3) intermediate detection: sampling and inspecting according to sampling rules, wherein the product is white particles; the RSD (relative standard deviation) at 6 points should be no greater than 2.0%; the product contains ibuprofen (by C)13H18O2Calculated) should be 19.0% to 21.0%; the drying weight loss can not exceed 1.5 percent; the intermediate granularity is measured by a double-screening method, and the sum of the intermediate granularity which can not pass through a No. 1 screen and the intermediate granularity which can pass through a No. 5 screen is not more than 15 percent of the test quantity; the dissolution rate (dissolution rate: the dissolution rate and degree of the active drug from common preparations such as tablets, capsules or granules and the like under specified conditions) of the granules is more than or equal to 85 percent of the marked amount within 15 minutes.
(11) Subpackaging: setting transverse sealing temperature (100-170 ℃), longitudinal sealing temperature (130-220 ℃) and compressed air range of 0.45-0.8 Mpa, filling qualified granules into a hopper of a racking machine, adjusting filling amount (1 g/bag, filling amount difference +/-9%) and operating speed of 180-220 bags/minute. And adjusting the batch number at the position of the rolling port, and starting a machine to pack the particles into the plastic film. Checking the loading amount every 60 minutes, and requiring tight sealing, no air leakage, clear and correct batch number.
(12) And (3) outer packaging: and executing according to the standard operating specification of the external packaging process. (13) And (7) warehousing.
The ibuprofen particles prepared by the method are evaluated, an evaluation report is provided, and the evaluation proves that the ibuprofen particles prepared by the method provided by the embodiment of the application have a good drug effect, no segregation phenomenon occurs and the dissolution performance is good.
The ibuprofen particles prepared by the method provided by the embodiment of the application are equivalent to the original ground medicine and have uniform quality. If the ibuprofen is prepared by other methods, for example, ibuprofen is not crushed and sieved, and raw and auxiliary materials are not sieved, so that the raw and auxiliary materials are not uniformly mixed, and finally the prepared particles have non-uniform content and do not meet the requirements of quality standards; or the proportion of the mixed liquid is changed, the prepared soft material has insufficient wettability or excessive wettability, and powder or excessive viscosity can be caused to be not granulated in the granulation process.
The recipe composition evaluated in the examples of the present application is as follows:
table 1: comparison of prescription compositions of ibuprofen granules
In table 1, the formulation of ibuprofen granules (0.2g) and the amounts of raw and auxiliary materials provided in the present application example all meet the amounts listed in the FDA-approved database for pharmaceutical inactive ingredients, and in the present application example, to control the maximum amount of inactive ingredients more strictly, the minimum value among the maximum amounts of approved dosage forms is selected, i.e., the amount of fumaric acid is selected to be 0.7mg in the capsule item.
In table 1, when the dosage of hydroxypropyl cellulose as a binder is less than 3%, more granular powder is obtained after extrusion and drying, and when the dosage of the binder is more than 3%, the extrudate obtained after soft material rotary extrusion is in a strip shape, the viscosity is higher, the extrudate is easy to adhere into large blocks in the shot blasting and rounding process, both the extrudate and the large blocks can be screened out in the whole granulation process, and the rejection rate is increased.
In table 1, when the amount of the disintegrant croscarmellose sodium is less than 3%, the dissolution rate and degree of the active drug ibuprofen in the granules may be reduced, which may affect the dissolution rate of the final granules.
The process verification batch samples (batch numbers: 34180601, 34180602, 34180603) continuously produced by the method provided by the embodiment of the application and the reference preparation (batch number: K64670) are subjected to comprehensive quality comparison research, and the comparison result shows that the preparation provided by the application and the reference preparation have consistent quality.
Summary of test results Table 2
In Table 2, C-022-01, C-022-02, C-022-03, C-022-04, C-022-05, C-022-06, C-022-07, C-022-08, and C-022-010 are impurities (Ibuprofen). Specific structural formulas, molecular formulas and molecular weights are shown in table 3.
TABLE 3
As can be seen from table 2, the comparison results demonstrate that the formulations provided herein are consistent in quality with the reference formulations.
In the influencing factor test, the ibuprofen granules provided by the embodiment of the application are packaged and placed for 5 and 10 days under the conditions of high temperature (50 ℃), high humidity (RH 75%, 25 ℃) and illumination (5000lx), and the quality indexes of the sample such as properties, dissolution rate, content, related substances, drying weight loss and the like all meet the regulations. In an accelerated test, the ibuprofen granules provided by the application are packaged in the market, and placed for 6 months under the conditions of the temperature of 40 +/-2 ℃ and the RH75 +/-5%, so that the quality indexes of the three batches of samples, such as the properties, the dissolution rate, the content, related substances, the drying weight loss and the like, meet the regulations. In a long-term test, the ibuprofen granules provided by the application are packaged commercially, and are placed for 36 months under the conditions of the temperature of 30 ℃ plus or minus 2 ℃ and the RH of 65 percent plus or minus 10 percent, and the test results show that the quality indexes of the three batches of samples, such as the properties, the dissolution rate, the content, the related substances, the drying weight loss and the like, all meet the requirements at present after 34 months.
The ibuprofen granules prepared by the method are subjected to random, open, two-preparation, double-cycle, cross-fasting and postprandial single administration biological equivalence tests on healthy human bodies.
In the fasting test, 62 healthy subjects are screened and grouped into 24 subjects, all the subjects complete the tests in two periods, the individual blood concentration data is completely collected and is included in the calculation and statistical analysis of pharmacokinetics and bioequivalence. ZK05 test subject has a blood sampling time window, and the blood sampling time points of the other test subjects are all in accordance with the planned collection time point or in the time window specified by the scheme, and the actual collection time points are adopted to calculate the PK parameters.
After 200mg of ibuprofen granules (test preparation or reference preparation) are orally taken by 24 healthy subjects in a fasting state, the Cmax (peak concentration of drug) and AUC0-t and AUC0- ∞ of ibuprofen in plasma are shown, wherein AUC0 is the representation of the plasma concentration of pharmaceutical research at a certain time point, 0-t is the representation within a certain time period, and is different from 0- ∞, namely the representation of plasma concentration at infinity. The ratio of the geometric mean values after logarithmic conversion is respectively: 111.41%, 100.96% and 100.99%. The corresponding 90% confidence intervals are 1 respectively04.98-118.24%, 97.85-104.17% and 97.88-104.19%, all of which are in the range of 80.00-125.00%, and meet the judgment standard of bioequivalence. Namely Ibuprofen Granules (200mg) provided by the embodiment of the application and a reference preparation Ibuprofen Granules (A), (B), (C), (
Specification: 20% of 1g) is tested by an fasting oral administration bioequivalence test and judged as a bioequivalent preparation.
A total of 66 healthy male subjects were screened in this postprandial test and included in 38 groups. Data collection of blood concentration of 38 individual subjects was complete and included in the safety data analysis set and PK analysis set. And (3) except the blood sampling point exceeding window 1h after the ZC20 subject takes the medicine, performing PK parameter calculation according to the actual acquisition time point when the other blood sampling time points accord with the planned acquisition time point or in the time window specified by the scheme.
After 38 healthy subjects orally take 200mg ibuprofen granules (test preparation or reference preparation) in the postprandial state, the ratio of the geometrical mean values of the plasma after logarithmic transformation of Cmax, AUC0-t and AUC0- ∞ of the ibuprofen granules are respectively as follows: 105.40%, 100.13% and 100.18%, wherein the corresponding 90% confidence intervals are 97.31% -114.17%, 97.71% -102.60% and 97.75% -102.66%, which are all in the range of 80.00-125.00%, and meet the judgment standard of bioequivalence. Namely, Ibuprofen Granules (200mg) provided in the examples of the present application were mixed with a reference formulation Ibuprofen Granules (specification: 20% 1g, trade name:
) The biological equivalent preparation is judged by the test of the biological equivalent test of the oral administration after meal.
The test results show that the ibuprofen granules produced by the method provided by the embodiment of the application and the reference preparation have bioequivalence in fasting state and postprandial administration state.
Then, the ibuprofen granules (0.2g) provided by the embodiment of the application are evaluated to meet the requirements of scientificity, integrity, consistency and authenticity in research and development, production process, stability investigation and the like; the sample for bioequivalence study (lot # 34180601) was produced in an oral solid dosage workshop that had acquired the drug manufacturing quality control code.
The above examples only show some embodiments of the present invention, and the description thereof is more specific and detailed, but not construed as limiting the scope of the present invention. It should be noted that, for a person skilled in the art, several variations and modifications can be made without departing from the inventive concept, which falls within the scope of the present invention. Therefore, the protection scope of the present patent shall be subject to the appended claims.
Claims (10)
1. An ibuprofen granule, comprising:
0.8 to 1.2 portions of ibuprofen, 3.0 to 4.0 portions of filling agent, 0.10 to 2 portions of adhesive and disintegrating agent, and 0.001 to 0.002 portion of flavoring agent and flavoring agent.
2. The ibuprofen particles of claim 1, wherein said ibuprofen particles comprise: 1 part by weight of ibuprofen, 3.7 parts by weight of filler, 0.15 part by weight of adhesive and disintegrant and 0.001 part by weight of flavoring agent and flavoring agent.
3. The ibuprofen granulate of claim 1, wherein said filler is lactose, said binder is hydroxypropylcellulose, said disintegrant is croscarmellose sodium, said flavoring agent is fumaric acid, and said flavoring agent is sodium saccharin.
4. The preparation method of the ibuprofen granules is characterized by comprising the following steps:
crushing the raw material medicines: crushing the ibuprofen raw material drug to preset fineness to obtain a first raw material drug;
raw and auxiliary material sieving: sieving the adhesive, the first raw material medicine and the filler to obtain raw and auxiliary materials with preset meshes;
mixing: adding the raw and auxiliary materials with preset meshes and the disintegrating agent into a mixing machine, mixing the raw and auxiliary materials with the preset meshes and the disintegrating agent into dry powder, and adding the mixed solution for wet mixing to obtain a soft material;
a granulation step: extruding the soft material through a granulator to obtain wet granules;
and (3) drying: drying the wet granules to obtain dry granules;
finishing the grains: and removing large particles and fine powder in the dry particles to obtain the target ibuprofen particles.
5. The method for preparing ibuprofen granules according to claim 4, wherein the step of pulverizing the raw material drugs comprises: and adding the ibuprofen raw material at a constant speed by a grinder under preset current and preset frequency at preset feeding frequency, and grinding to preset fineness.
6. The method for preparing ibuprofen granules according to claim 5, wherein the predetermined fineness is 2 μm or more and 18 μm or less from D50 and 56 μm or less from D90 and 4 μm or less.
7. The method of claim 4, wherein the predetermined mesh size is 20 mesh.
8. The method of preparing ibuprofen granules according to claim 4, further comprising the step of preparing a mixed solution: and mixing the flavoring agent, the flavoring agent and the purified water according to the proportion of 1:1:1200 to obtain the mixed solution.
9. The method of preparing ibuprofen granules according to claim 4, further comprising the steps of ingredient mixing: adding the raw and auxiliary materials with the preset mesh number and the disintegrating agent into a mixer for dry mixing; adding the mixed solution, and wet mixing to obtain a soft material.
10. The method of preparing ibuprofen granules according to claim 4, further comprising the step of total mixing: adding the target ibuprofen particles into a mixer for integral mixing;
preferably, the method further comprises an intermediate detection step: and sampling and detecting the target ibuprofen particles according to a sampling rule, and taking the ibuprofen particles meeting the detection standard as the target ibuprofen particles.
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| CN115581673A (en) * | 2022-10-28 | 2023-01-10 | 浙江康恩贝制药股份有限公司 | Ibuprofen granule and preparation method thereof |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5104648A (en) * | 1989-02-02 | 1992-04-14 | Mallinckrodt Specialty Chemicals Company | High ibuprofen content granulations |
| US20060034919A1 (en) * | 2004-06-30 | 2006-02-16 | Hu Patrick C | High ibuprofen content granules and their preparation and their use in pharmaceutical dosage forms |
| CN112137966A (en) * | 2020-10-28 | 2020-12-29 | 哈药集团技术中心 | Ibuprofen granule and preparation method thereof |
| CN112351772A (en) * | 2018-06-26 | 2021-02-09 | 日本脏器制药株式会社 | Method for treating bulk drug particles with inconsistent particle sizes |
-
2021
- 2021-05-26 CN CN202110579189.4A patent/CN113318081A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5104648A (en) * | 1989-02-02 | 1992-04-14 | Mallinckrodt Specialty Chemicals Company | High ibuprofen content granulations |
| US20060034919A1 (en) * | 2004-06-30 | 2006-02-16 | Hu Patrick C | High ibuprofen content granules and their preparation and their use in pharmaceutical dosage forms |
| CN112351772A (en) * | 2018-06-26 | 2021-02-09 | 日本脏器制药株式会社 | Method for treating bulk drug particles with inconsistent particle sizes |
| CN112137966A (en) * | 2020-10-28 | 2020-12-29 | 哈药集团技术中心 | Ibuprofen granule and preparation method thereof |
Non-Patent Citations (1)
| Title |
|---|
| 佚名: "布洛芬颗粒说明书", 《百度文库》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115581673A (en) * | 2022-10-28 | 2023-01-10 | 浙江康恩贝制药股份有限公司 | Ibuprofen granule and preparation method thereof |
| CN115581673B (en) * | 2022-10-28 | 2024-02-02 | 浙江康恩贝制药股份有限公司 | Ibuprofen granule and preparation method thereof |
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