CN111728943A - Stable cefaclor granule pharmaceutical composition - Google Patents

Stable cefaclor granule pharmaceutical composition Download PDF

Info

Publication number
CN111728943A
CN111728943A CN202010585709.8A CN202010585709A CN111728943A CN 111728943 A CN111728943 A CN 111728943A CN 202010585709 A CN202010585709 A CN 202010585709A CN 111728943 A CN111728943 A CN 111728943A
Authority
CN
China
Prior art keywords
cefaclor
pharmaceutical composition
granules
silicon dioxide
steps
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
CN202010585709.8A
Other languages
Chinese (zh)
Inventor
祝少良
姚忠磊
宋莹雪
何卫强
姚芳
贝晶
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Disha Pharmaceutical Group Co Ltd
Original Assignee
Dijia Pharmaceutical Group Co ltd
Disha Pharmaceutical Group Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Dijia Pharmaceutical Group Co ltd, Disha Pharmaceutical Group Co Ltd filed Critical Dijia Pharmaceutical Group Co ltd
Priority to CN202010585709.8A priority Critical patent/CN111728943A/en
Publication of CN111728943A publication Critical patent/CN111728943A/en
Pending legal-status Critical Current

Links

Images

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • 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
    • A61K9/1611—Inorganic compounds
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
    • A61K31/542—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/545—Compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins, cefaclor, or cephalexine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents

Abstract

The invention relates to a stable cefaclor granule pharmaceutical composition, and belongs to the technical field of pharmaceutical preparations. The invention provides a stable cefaclor granule pharmaceutical composition, and the technical scheme of the invention is as follows: a pharmaceutical composition of cefaclor granules comprising, in unit dose form: cefaclor (as C)15H14ClN3O4S) 6.5-17.8%, silicon dioxide 1-5%, filler 65-90%, adhesive 1-5%, disintegrating agent 1-5%, wherein the percentages are mass percentages.

Description

Stable cefaclor granule pharmaceutical composition
Technical Field
The invention relates to a stable cefaclor granule pharmaceutical composition, and belongs to the technical field of pharmaceutical preparations.
Background
Cefaclor is free from celecoxibThe cephalosporin is developed in laboratories, is the second generation cephalosporin, has broad-spectrum antibacterial effect, has the same action mechanism as other cephalosporins, and achieves the bactericidal effect mainly by inhibiting the synthesis of cell walls. Marketed in countries such as the United states and Japan, and sold in many countries including China, and the trade names are Ceclor and Hirtina®Distaclor, kefral, keflor, koufle, etc. At present, dry suspension, capsules, tablets, granules and other various formulations are sold in China.
According to fine cefaclor granule IF documents disclosed by Japan salt Yeyi company and patent CN108743547A, cefaclor is unstable to moisture and heat, and the phenomena of obvious content reduction and impurity increase occur to different degrees in the product storage process. The drug content is a key index of drug effect, drug impurities are important sources of drug side effects and adverse reactions, and the characteristic of poor stability of cefaclor brings hidden troubles to the effectiveness and safety of the drug.
CN103330685B and CN108743547A adopt a drug inclusion technology, and the drug cefaclor is treated in a mode of wrapping the drug by the inclusion compound, so that the drug degradation speed is reduced, but the process adopts the drug inclusion technology and needs to add steps of reduced pressure drying and the like, so that the process complexity is improved, and the production cost is increased.
Silicon dioxide is a common auxiliary material in pharmaceutical preparations, and can be used as a glidant and a disintegrant in solid preparations according to the description of an auxiliary material manual (R.C. Rou, P.J. Ski, P.J. Weller. pharmaceutical auxiliary material manual [ M ]. Beijing: chemical industry Press, 2005.), and the recommended dosage is 0.1-0.5% when the silicon dioxide is used as the glidant.
CN201510905949.0 proposes a method for absorbing liquid butylphthalide by using highly adsorptive silicon dioxide powder as a drug carrier with a high proportion (the mass ratio of butylphthalide to silicon dioxide is 0.1-4:1, namely the silicon dioxide accounts for 90.9% of the total weight in the drug loading process), which solves the problems of complicated component, small drug loading amount, poor drug stability, complicated preparation process and long time consumption of a solid formulation of butylphthalide, however, the silicon dioxide with high pore volume needs to be selected as the carrier (such as SYLOID 244 FP or CAB-O-SIL M-5P), the cost is higher, a high dust environment is easily formed due to the very fine particle size and large using amount of the silicon dioxide with high pore volume, the risk of dust explosion needs to be concerned during the production of the product, has higher explosion-proof requirements on equipment and operation, and simultaneously has potential respiratory irritation and even pulmonary fibrosis risk to production personnel.
CN201810929288 discloses a reinforcement system of micronized silicon dioxide, nanocrystallized silicon dioxide and maltodextrin in a specific proportion, and the moisture absorption rate of the traditional Chinese medicine composition is improved by utilizing the effect of the silicon dioxide on improving the hygroscopicity of the medicine, so that the stability of the medicine is improved; CN107213127B mentions in the specification that "silica can also alleviate the hygroscopicity of sorbitol to some extent and improve the stability of solid dispersion".
Disclosure of Invention
The purpose of the invention is as follows: aiming at the defects of the prior art, the stable cefaclor granule composition is provided, and a convincing medicine is provided for clinic.
When the silicon dioxide is used as the glidant to study a prescription of cefaclor granules, the silicon dioxide accounting for 1-5% of the total weight of the composition is unexpectedly found to play a role in glidant and have positive significance on the stability of cefaclor when the recommended dosage (0.1-0.5%) is obviously exceeded.
It has also been found that the stability of the drug is not enhanced by the anti-hygroscopic properties of silica. As shown in test example 2: when the naked particles of the patent examples and the comparative examples are placed in a high-humidity environment, the water content is close to 4% in the 47 th hour; the contents of the products in the examples and the related substances are not obviously changed relative to 0 month, the contents of the products in the comparative examples show a descending trend, and the contents of the related substances show an ascending trend relative to 0 month, which shows that the products in the examples obtain unexpected stability effects.
The principle of the present invention is not clear, and it is speculated that the principle that silica in the present invention amount range contributes to the improvement of cefaclor stability may be: the chemical reaction of the drug is generally fast under the intervention of a solvent (such as water vapor), and the chemical reaction on the solid-solid surface is very slow. Because the surface area of the silicon dioxide is larger, huge intermolecular force is easy to form with other raw and auxiliary materials, so that the particle structure is more compact, and the strength of water-oxygen exchange between the particles and the outside is reduced; the silicon dioxide has a loose structure and is easy to form countless hydrophobic capillary-like structures in the particles, and water molecules passing through the surface layers of the particles are easy to transport to the interior of a silicon dioxide 'pipeline' through the capillary action; the silicon dioxide has strong adsorbability, so that water molecules in the 'pipeline' are difficult to escape near the 'capillary' to form a stable structure with relatively saturated moisture. Under the combined action of the two, the reaction rate of oxidizing, hydrolyzing and the like of the cefaclor and oxygen molecules or water molecules and the like is reduced, and the stability of the medicament is improved. This speculation is not bound by theory, but is merely one possible theoretical explanation of the "unexpected discovery" of the present invention.
The technical scheme of the invention is as follows:
a pharmaceutical composition of cefaclor granules comprising, in unit dose form: cefaclor (as C)15H14ClN3O4S) 6.5-17.8%, silicon dioxide 1-5%, filler 65-90%, adhesive 1-5%, disintegrating agent 1-5%, wherein the percentages are mass percentages.
The total weight of the cefaclor granule pharmaceutical composition of the invention in unit dose is not more than 2.5 g.
The cefaclor granule pharmaceutical composition disclosed by the invention has the preferable silicon dioxide dosage of 2-4%.
The filler is selected from one or more of mannitol, sucrose, corn starch and dextrin.
The adhesive is one or more selected from methylcellulose, ethyl cellulose, hypromellose, hyprolose, and polyvinylpyrrolidone; the binder may be added in dry powder form or may be added after dissolving all or part of it in the wetting agent.
The disintegrant is selected from one or more of croscarmellose sodium, sodium carboxymethyl starch, crospovidone, and low substituted hydroxypropyl cellulose.
The pharmaceutical composition of cefaclor granules according to the invention may also contain suitable amounts of pH adjusting agents and/or colouring agents.
The pH regulator is selected from one or more of malic acid, fumaric acid, acetic acid, tartaric acid, hydrochloric acid, phosphoric acid and lactic acid, and accounts for 0.1-0.5% of the total weight of the composition; the coloring agent is one or more of ferric oxide, carotene, cochineal, lemon yellow and sunset yellow, and accounts for 0.2-0.5% of the total weight of the composition. The purpose of adding the pH regulator is to enable the pharmaceutical composition to meet the pharmacopoeia requirement of pH = 3.0-5.0.
The cefaclor granule pharmaceutical composition can be added with a flavoring agent, wherein the flavoring agent is selected from one or more of simple syrup, sorbitol, aspartame, sucralose, stevioside, glucose, xylitol, maltitol and essence; the flavoring agent accounts for 0.2-2% of the total weight of the composition.
The wetting agent of the pharmaceutical composition of cefaclor granules is water or ethanol water solution, and is removed in the drying process.
The preparation method of the cefaclor granule composition comprises the following steps:
step 1. preparation of additional adjuvants (e.g. wetting agent/binder)
Step 2, adding the cefaclor, the filler, the disintegrating agent, the silicon dioxide and part or all of the adhesive in the prescription amount into a granulator and uniformly mixing;
step 3, adding additional auxiliary materials such as wetting agents or prepared partial/whole adhesives into the granulator with the materials in the step 2 under stirring to prepare soft materials;
step 4, wetting the soft material prepared in the step 3 into granules by using a swing granulator or a quick granulating machine;
step 5, transferring the wet particles to a boiling dryer or an oven for drying, wherein the temperature of the materials is controlled not to exceed 60 ℃ during drying;
step 6, screening out the particles which do not meet the requirements (the sum of the particles which can not pass through a standard sieve with 10 meshes and the particles which can pass through a standard sieve with 80 meshes does not exceed 15 percent) by using a screening machine to complete the particles
And 7, mixing the particles obtained in the step 6 uniformly, and subpackaging the particles according to requirements to obtain a finished product.
According to the preparation method, the flavoring agent, the pH regulator and/or the coloring agent can be added in the step 2, or can be dissolved in the wetting agent and then added in the step 3.
The dosage of the silicon dioxide adopted by the invention is 1-5% of the total weight of the pharmaceutical composition, preferably 2-4%, and obviously exceeds the recommended dosage (0.1-0.5%), but the maximum total dosage meets the IIG and Japanese additive typical dosage requirements published by FDA, and the administration safety of patients can be guaranteed.
After stability examination under accelerated and intermediate conditions, as shown in test example 1:
the stability test under the accelerated condition shows that: through the stability examination for 6 months, the content of the product in the example 2 adopting the patent is reduced less and the impurity growth is obviously slower than that of the product in the comparative example 3 not adopting the patent during the stability period; the pharmaceutical composition prepared by the patent (examples 1-7) is compared with a reference preparation of the most similar dosage form, namely the Hikeluo®The (cefaclor dry suspension) has smaller impurity amplification and content reduction, and shows remarkable quality advantage;
the stability test of the intermediate condition shows that: through 12-month stability examination, example 2 is superior to examples 1 and 4, and shows that the better application effect can be realized by the silicon dioxide accounting for 2-4% of the total weight, and the examples are superior to the comparative example, which shows that the technology of the invention obtains unexpected effect.
Comparative examples 1 and 2 did not give the desired results, indicating that silica concentrations above the patent were not favorable for the process to proceed smoothly (comparative example 1) and silica concentrations below the patent did not meet the stability requirements (comparative example 2).
Description of the drawings:
FIG. 1: graph of moisture absorption weight gain rate of cefaclor granules in high humidity challenge test.
Has the advantages that:
in conclusion, compared with the prior art, the pharmaceutical composition provided by the invention effectively improves the stability of the medicine, and is beneficial to improving the effectiveness and safety of the medicine; the method has low production cost and simple and convenient operation, and the silicon dioxide accounts for far less than CN201510905949.0 of the total weight, thereby avoiding the potential risk of forming a high-dust environment and harming workers.
Detailed Description
The following examples are only preferred embodiments of the present invention, and are not intended to limit the scope of the present invention, but all changes that can be made by applying the principles of the present invention and without inventive work on the basis thereof shall fall within the scope of the present invention.
Example 1:
prescription:
Figure 1
the preparation method comprises the following steps:
step 1, an additional auxiliary material preparation method comprises the following steps: adding the malic acid with the prescription amount into the purified water with the prescription amount under stirring, and uniformly stirring to obtain the finished product.
Step 2, adding raw and auxiliary materials for premixing: adding the cefaclor, silicon dioxide, hydroxypropyl methylcellulose, low-substituted hydroxypropyl cellulose, mannitol, corn starch, aspartame and natural strawberry powder essence into a wet granulator, and uniformly mixing.
Step 3, preparing a soft material by a wet method: adding the additional auxiliary materials obtained in the step 1 into the mixture obtained in the step 2 under stirring to prepare a proper soft material.
Step 4, preparing wet particles: and (4) wetting the soft material prepared in the step (3) by using a swinging granulator.
And step 5, drying: transferring the wet granules to a fluidized bed dryer, drying at the material temperature of 55 ℃, stopping the machine when the moisture of the granules is less than or equal to 1.5 percent, and discharging.
Step 6, granulating: the granules were sieved using a standard sieve, requiring that the sum of the granules that could not pass through a 10 mesh standard sieve and those that could pass through an 80 mesh standard sieve did not exceed 15%.
And 7, subpackaging: and 6, uniformly mixing the particles obtained in the step 6, and subpackaging according to requirements to obtain a finished product.
Example 2:
prescription:
Figure 2
the preparation method comprises the following steps:
step 1, an additional auxiliary material preparation method comprises the following steps: adding the malic acid with the prescription amount into the purified water with the prescription amount under stirring, and uniformly stirring to obtain the finished product.
Steps 2 to 7 are the same as in example 1.
Example 3:
prescription:
Figure 3
the preparation method comprises the following steps:
step 1, an additional auxiliary material preparation method comprises the following steps: adding the malic acid with the prescription amount into the ethanol with the prescription amount of 20 percent under stirring, and uniformly stirring to obtain the finished product.
Steps 2 to 7 are the same as in example 1.
Example 4:
prescription:
Figure 4
the preparation method comprises the following steps:
step 1, an additional auxiliary material preparation method comprises the following steps: adding the malic acid with the prescription amount into the purified water with the prescription amount under stirring, and uniformly stirring to obtain the finished product.
Steps 2 to 7 are the same as in example 1.
Example 5:
prescription:
Figure 5
the preparation method comprises the following steps:
step 1, an additional auxiliary material preparation method comprises the following steps: adding the prescription amount of phosphoric acid and polyvinylpyrrolidone (K30) into the prescription amount of purified water under stirring, and stirring until the solution is uniform, clear and transparent.
Steps 2 to 7 are the same as in example 1.
Example 6:
prescription:
Figure 6
the preparation method comprises the following steps:
step 1, an additional auxiliary material preparation method comprises the following steps: adding the lemon yellow and the phosphoric acid into the purified water according to the prescription amount under stirring, and stirring until the solution is uniform, clear and transparent.
Steps 2 to 7 are the same as in example 1.
Example 7:
prescription:
Figure 7
the preparation method comprises the following steps:
step 1, an additional auxiliary material preparation method comprises the following steps: adding the lemon yellow and the phosphoric acid into the purified water according to the prescription amount under stirring, and stirring until the solution is uniform, clear and transparent.
Steps 2 to 7 are the same as in example 1.
Comparative example 1: the silicon dioxide content is higher than 5%.
Prescription:
Figure 8
the preparation method comprises the following steps:
step 1, an additional auxiliary material preparation method comprises the following steps: adding the malic acid with the prescription amount into the purified water with the prescription amount under stirring, and uniformly stirring to obtain the finished product.
Steps 2 to 3 are the same as in example 1.
As a result: the soft material prepared in the step 3 is too wet and too sticky, cannot be granulated, and does not meet the process requirement of the step 4, which shows that the excessive silicon dioxide dosage influences the realizability of the product process.
Comparative example 2: the amount of silicon dioxide is less than 1%.
Prescription:
Figure 9
the preparation method comprises the following steps:
step 1, an additional auxiliary material preparation method comprises the following steps: adding the malic acid with the prescription amount into the purified water with the prescription amount under stirring, and uniformly stirring to obtain the finished product.
Steps 2 to 7 are the same as in example 1.
Comparative example 3:
prescription: referring to example 2, talc was used in place of silica in the same amount.
Figure 10
The preparation method comprises the following steps:
step 1, an additional auxiliary material preparation method comprises the following steps: adding the malic acid with the prescription amount into the purified water with the prescription amount under stirring, and uniformly stirring to obtain the finished product.
Steps 2 to 7 are the same as in example 1.
Test example 1 the products of examples 1 to 7 and the products of comparative examples 2 to 3 were tested according to the test methods prescribed in the pharmacopoeia, and the data are reported in table 1.
TABLE 1 summary of the test results for the examples and comparative examples
Figure 11
Description of the drawings: table 1 dissolution rates are 30 minutes, 6 tablets, respectively.
Table 1 the data illustrates: except for the fact that the process of comparative example 1 cannot be realized, all the examples and comparative examples shown in the patent can successfully obtain cefaclor granules meeting the internal control requirement.
Test example 2 stability testing of cefaclor granules
The products of examples 1-7, the products of comparative examples 2-3 and reference preparations with similar production dates were used for the production of hickory®And (5) synchronously carrying out stability examination, and comparing the examination results with tables 2 and 3.
Examination conditions were as follows: acceleration conditions (0, 1, 2, 3 and 6 months) and the results are shown in table 2;
intermediate conditions ( months 0, 3, 6, 9 and 12) and the results are shown in Table 3.
And (4) investigating items: content, related substances (maximum individual impurities, total impurities).
The content inspection method comprises the following steps: referring to a USP42 cefaclor dry suspension content detection method, a chromatographic column: shimadzu ODS-3V4.6 x 250mm,5 μm, mobile phase: a mixed solution of a buffer (mixed with 780ml of water and 10ml of triethylamine, dissolved by adding 1g of sodium pentane sulfonate, and adjusted to pH 2.5 +/-0.1 by using phosphoric acid) and 220ml of methanol is used as a mobile phase, and the detection wavelength: 265 nm.
The content requirement is as follows: 90.0 to 110.0 percent.
The related substance detection method comprises the following steps: referring to the detection method of related substances of cefaclor dry suspension of U.S. USP42, chromatographic columns: shimadzu ODS-3V 4.6X 250mm,5 μm, mobile phase A: taking 7.8g of sodium dihydrogen phosphate dihydrate, adding water to dissolve and dilute the sodium dihydrogen phosphate dihydrate to 1000ml, and adjusting the pH value to 4.0 by using phosphoric acid; mobile phase B: mobile phase a-acetonitrile (55: 45), detection wavelength: 220 nm.
The requirements of related substances are as follows: the maximum single impurity is less than or equal to 2.0 percent; the total impurities are less than or equal to 3.0 percent.
TABLE 2 summary of accelerated condition examination results of cefaclor granules
Figure DEST_PATH_IMAGE012
Note: "/" indicates not done;
the data in table 2 show that:
during the accelerated investigation period of 6 months, the content degradation of the products in the examples 1-7 has no significant difference; the maximum single impurity of related substances does not exceed 0.3 percent, and the total impurity does not exceed 1.0 percent; while the maximum single impurity of the products of comparative examples 2 and 3 is 0.39%, 0.49%, and the total impurity is 2.7%, 3.77%; examples 1 to 7 products and commercial Hidilo®Compared with the prior art, the method has the advantages of less content reduction, slower impurity growth and obvious quality advantage.
Compared with the product of the comparative example 2, the products of the examples 1 to 7 show that when the usage amount of the silicon dioxide is less than 1 weight percent, the content of the silicon dioxide is obviously reduced when the silicon dioxide is placed under an accelerated condition for 6 months, and the total impurities are obviously increased, which indicates that the silicon dioxide usage amount is less than 1 percent, the effect of improving the stability of cefaclor cannot be achieved; compared with comparative example 3, it can be seen that when silicon dioxide is not used as a glidant, other glidants (such as talcum powder) have no effect of improving stability of cefaclor; as described above, comparative example 1 shows that when the amount of silica is more than 5% by weight, the soft material is excessively wet, which hinders the smooth progress of the process.
The data show that a sample prepared from 1-5% of silicon dioxide, 1-3% of disintegrating agent and adhesive, 65-90% of filler, 0.2-2% of flavoring agent and a proper amount of pH regulator and/or colorant which can be added if necessary has good stability, and the product quality is obviously improved.
TABLE 3 summary of intermediate Condition examination results of cefaclor granules
Figure DEST_PATH_IMAGE013
Note: 0 month-12 month rate of change = (12 month value-0 month value)/0 month value x100%
The data in table 3 show that:
during 12 months of intermediate condition investigation, the embodiment 2 with the silicon dioxide amount accounting for 2-4% of the total weight of the composition has the impurity growth change rate of plus 50%, and the embodiments 1 and 4 with the silicon dioxide amount accounting for 1% and 5% of the total weight of the composition respectively have the impurity growth change rate of plus 160%, so the conclusion that the silicon dioxide amount adopted by the invention accounts for 1-5% of the total weight of the composition, and preferably accounts for 2-4% of the content of a unit package is true; the maximum single and total heterogrowth rates of examples 1, 2, 4 are all significantly better than comparative example 3.
Test example 3 high humidity challenge test
About 20g of each of the products of examples 1, 2, 4, 6, 7 and comparative example 3 was uniformly spread in a petri dish, respectively placed in an open and bare environment of 92.5% RH saturated potassium nitrate, and samples were taken at the following times to measure the moisture of the granules (measured by a rapid moisture meter at 80 ℃), and the contents of the products and related substances were measured at 47 hours, respectively, and the results are recorded in Table 4.
Table 4 summary of high humidity challenge test results
Figure DEST_PATH_IMAGE014
Table 4 the results show: under the condition of 92.5% RH humidity, the water content of each sample reaches about 4.0% in 47 hours, and the water absorption rate increment of each sample is not obviously different from 0 hour → 47 hours, which shows that the moisture absorption resistance of the product obtained by adopting the technology of the invention is not improved compared with that of the comparative example 3.
The content and related substances of the product in the embodiment are almost unchanged after the product is placed for 47 hours, and the content and related substances are equivalent to the stability 0-month test result (test example 2) in the embodiments 1-7; the content of the product of comparative example 3 is reduced after the product is placed for 47h, and related substances are increased. The product of the invention obviously improves the degradation tendency of the cefaclor granules.

Claims (6)

1. A pharmaceutical composition of cefaclor granules, wherein the composition comprises, in unit dose: 6.5-17.8% of cefaclor, 1-5% of silicon dioxide, 65-90% of filler, 1-5% of adhesive and 1-5% of disintegrating agent, wherein the percentages are mass percentages.
2. The cefaclor granule pharmaceutical composition as claimed in claim 1, wherein the cefaclor granule pharmaceutical composition comprises 2-4% of silicon dioxide.
3. The cefaclor granule pharmaceutical composition as claimed in claim 1, wherein the bulking agent is selected from one or more of mannitol, sucrose, corn starch and dextrin.
4. The cefaclor granule pharmaceutical composition as claimed in claim 1, wherein the binder is selected from one or more of methylcellulose, ethylcellulose, hypromellose, hyprolose and polyvinylpyrrolidone; the binder may be added in dry powder form or may be added after dissolving all or part of it in the wetting agent.
5. The cefaclor granule pharmaceutical composition as claimed in claim 1, wherein the disintegrant is selected from one or more of croscarmellose sodium, sodium carboxymethyl starch, crospovidone, and low substituted hydroxypropylcellulose.
6. A process for the preparation of a pharmaceutical composition of cefaclor granules according to claim 1, characterized by the steps of:
step 1, preparing additional auxiliary materials (such as wetting agents/adhesives);
step 2, adding cefaclor, a filler, a disintegrating agent, silicon dioxide and part or all of an adhesive into a granulator and uniformly mixing;
step 3, adding additional auxiliary materials such as wetting agents or prepared partial/whole adhesives into the granulator with the materials in the step 2 under stirring to prepare soft materials;
step 4, wetting the soft material prepared in the step 3 into granules by using a swing granulator or a quick granulating machine;
step 5, transferring the wet particles to a boiling dryer or an oven for drying, wherein the drying temperature is not more than 60 ℃;
step 6, straightening granules, wherein the sum of the granules which cannot pass through a 10-mesh standard sieve and the granules which can pass through an 80-mesh standard sieve is not more than 15%;
and 7, mixing the particles obtained in the step 6 uniformly, and subpackaging the particles according to requirements to obtain a finished product.
CN202010585709.8A 2020-06-24 2020-06-24 Stable cefaclor granule pharmaceutical composition Pending CN111728943A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202010585709.8A CN111728943A (en) 2020-06-24 2020-06-24 Stable cefaclor granule pharmaceutical composition

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202010585709.8A CN111728943A (en) 2020-06-24 2020-06-24 Stable cefaclor granule pharmaceutical composition

Publications (1)

Publication Number Publication Date
CN111728943A true CN111728943A (en) 2020-10-02

Family

ID=72650888

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202010585709.8A Pending CN111728943A (en) 2020-06-24 2020-06-24 Stable cefaclor granule pharmaceutical composition

Country Status (1)

Country Link
CN (1) CN111728943A (en)

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103142506A (en) * 2013-04-03 2013-06-12 天津医药集团津康制药有限公司 Cefpodoxime proxetil granules and preparation method thereof
CN103349646A (en) * 2013-05-24 2013-10-16 海口市制药厂有限公司 Medicinal composition containing cefaclor particles, and preparation method and application thereof
CN108743547A (en) * 2018-06-28 2018-11-06 苏州中联化学制药有限公司 A kind of content of cefaclor granules and preparation method thereof

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103142506A (en) * 2013-04-03 2013-06-12 天津医药集团津康制药有限公司 Cefpodoxime proxetil granules and preparation method thereof
CN103349646A (en) * 2013-05-24 2013-10-16 海口市制药厂有限公司 Medicinal composition containing cefaclor particles, and preparation method and application thereof
CN108743547A (en) * 2018-06-28 2018-11-06 苏州中联化学制药有限公司 A kind of content of cefaclor granules and preparation method thereof

Similar Documents

Publication Publication Date Title
SK155194A3 (en) Gastro-protected stable omeprazole composition in the form of microgranules and process for their production
CN102438595A (en) Pharmaceutical formulations comprising nitrocatechol derivatives and methods of making the same
CN112220770B (en) Pharmaceutical composition of selepag and preparation method thereof
CN109432022B (en) Pharmaceutical composition containing valnemadex tartrate and preparation method thereof
US9387172B2 (en) Solid dosage form comprising micronized cytisine and its production method
CN109908104B (en) Amoxicillin capsule and preparation method thereof
CN111728943A (en) Stable cefaclor granule pharmaceutical composition
CN106860404A (en) A kind of sildenafil citrate taste masking resin complexes and its application
JPH0328404B2 (en)
CN103845332B (en) A kind of Dasatinib Pharmaceutical composition and preparation method thereof
CN105919960B (en) A kind of roxithromycin dispersing tablet and preparation method thereof
CN106860408B (en) Glimepiride tablet
US3326760A (en) Choline salicylate polygalacturonate therapy
CN111603450B (en) Isosorbide mononitrate tablet and preparation process thereof
EP2915526A1 (en) Pharmaceutical compositions comprising anagrelide
CN108498481B (en) Cefixime composition and preparation method thereof
CN113230226A (en) Tinidazole tablet and preparation method thereof
CN112618508A (en) Stable amorphous sildenafil citrate tablet and production process thereof
KR101760278B1 (en) Process for preparing sustained release microsphere including eperisone as active ingredient
CN104983702A (en) Atorvastatin calcium composition tablet for treating hypercholesterolemia
CN112843001B (en) Amlodipine preparation and preparation method thereof
CN104644601B (en) Capecitabine tablet
CN113893222B (en) Pharmaceutical composition and preparation method and application thereof
CN115569124B (en) Selpatinib capsule composition and preparation method thereof
CN115554255B (en) High-stability folic acid tablet and preparation method thereof

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
TA01 Transfer of patent application right
TA01 Transfer of patent application right

Effective date of registration: 20210906

Address after: No.1 Qingdao South Road, Weihai Economic and Technological Development Zone, Shandong Province

Applicant after: DISHA PHARMACEUTICAL GROUP Co.,Ltd.

Address before: No.1 Qingdao South Road, Weihai Economic and Technological Development Zone, Shandong Province

Applicant before: DISHA PHARMACEUTICAL GROUP Co.,Ltd.

Applicant before: Dijia Pharmaceutical Group Co.,Ltd.

RJ01 Rejection of invention patent application after publication
RJ01 Rejection of invention patent application after publication

Application publication date: 20201002