CN115804757A - Cefdinir granules and preparation method thereof - Google Patents
Cefdinir granules and preparation method thereof Download PDFInfo
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- CN115804757A CN115804757A CN202111072409.0A CN202111072409A CN115804757A CN 115804757 A CN115804757 A CN 115804757A CN 202111072409 A CN202111072409 A CN 202111072409A CN 115804757 A CN115804757 A CN 115804757A
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- cefdinir
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- dextrin
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Abstract
The invention discloses cefdinir granules and a preparation method thereof, and belongs to the field of pharmaceutical preparations. The cefdinir granules are prepared from cefdinir, sucrose, dextrin, lactose, hydroxypropyl cellulose and silicon dioxide. According to the properties of cefdinir, the invention designs and preferably selects the prescription composition and dosage matched with the cefdinir from the aspect of pharmaceutics, and prepares the cefdinir granules by adopting a high-speed shearing wet granulation technology, thereby obtaining the cefdinir granules with high particle forming rate, good fluidity, small hygroscopicity and high melting rate.
Description
Technical Field
The invention belongs to the field of pharmaceutical preparations, and particularly relates to cefdinir granules and a preparation method thereof.
Background
Cefdinir (Cefdinir) is a third-generation oral cephalosporin developed on the basis of cefixime, has the advantages of wide antibacterial spectrum, strong antibacterial activity, good clinical curative effect, low toxicity, less anaphylactic reaction and convenient use, can be clinically used for skin and soft tissue infection, respiratory tract infection, urinary tract infection, otorhinolaryngology infection, scarlet fever and the like, and is widely used. Cefdinir has poor water solubility and stability, and the bioavailability and stability need to be improved by means of preparation.
The cefdinir has five dosage forms of tablets, dispersible tablets, capsules, dry suspensions and fine granules worldwide. Since the physiological status of children is different from that of adults, the absorption, distribution, metabolism and excretion capacities of the drugs are different in each stage of growth and development of children, so that the dosage of children patients is different from that of adults. Wherein the cefdinir fine granule is specially used for children, and is convenient and flexible to administer. At present, the preparation variety of the fine particle preparation is not available in China, the problem of 'lack of medical services and medicines' in pediatrics is very serious, the cefdinir preparation specially used for children is not available at present, and the Japanese cefdinir fine particle preparation is not imported into China, so that research and development on the cefdinir granule special for children are necessary on the basis of the Japanese cefdinir fine particle preparation, and the majority of pediatric patients can benefit early.
Disclosure of Invention
Aiming at the defects of the existing cefdinir preparation varieties, the invention aims to provide a cefdinir granule and a preparation method thereof, so that the cefdinir granule can improve the stability and dissolution rate of cefdinir and improve the compliance and bioavailability of cefdinir.
In order to achieve the purpose, the invention adopts the following technical scheme:
a cefdinir granule comprises the following raw materials: cefdinir, sucrose, dextrin, lactose, hydroxypropyl cellulose and silicon dioxide.
Aiming at the defects of poor solubility, flowability and stability of cefdinir bulk drugs, the cefdinir granules are prepared from sucrose, dextrin, lactose, hydroxypropyl cellulose and silicon dioxide, and through comparative study, the influence of each component is investigated, and the prescription composition of the cefdinir granules is optimized.
Preferably, the raw materials comprise the following components in parts by weight: 5-30 parts of cefdinir, 40-80 parts of cane sugar, 5-20 parts of dextrin, 20-40 parts of lactose, 1-15 parts of hydroxypropyl cellulose and 1-10 parts of superfine silica gel powder.
More preferably, the raw materials comprise, in parts by weight: 20 parts of cefdinir, 50 parts of cane sugar, 10 parts of dextrin, 10 parts of lactose, 7 parts of hydroxypropyl cellulose and 3 parts of superfine silica powder.
Preferably, the hydroxypropyl cellulose is selected from HPC-SSL, HPC-SL or HPC-L.
More preferably, the hydroxypropyl cellulose is HPC-SSL.
The invention also provides a preparation process of the cefdinir granules, which takes cefdinir, sucrose, dextrin, lactose, hydroxypropyl cellulose and silicon dioxide as preparation components. Sieving the auxiliary materials with a 60-mesh sieve for later use, weighing cefdinir, sucrose, dextrin, lactose, hydroxypropyl cellulose and silicon dioxide, fully mixing, placing in a wet granulation mixer, setting the rotating speed of a stirring knife and a shearing knife, and opening for a period of time to uniformly mix the materials. Adjusting the rotating speed of the stirring knife and the shearing knife, setting the flow rate of a peristaltic pump and the atomization pressure, adding the wetting agent into the materials at a certain flow rate, preparing a soft material through high-speed shearing, and sieving with a 40-mesh sieve to perform wet granulation. And (3) placing the wet granules in a fluidized bed, and drying at 50 ℃ air inlet temperature until the moisture is less than 2% to obtain dry granules. And (4) finishing the dry granules by using a 30-mesh sieve to obtain the cefdinir granules.
In the present invention, propylene glycol and/or an aqueous solution is used as the wetting agent. Because cefdinir is sensitive to water, the stability of the preparation can be improved by using alcohol as a wetting agent, and the viscosity excited by using pure water as the wetting agent is large and difficult to operate, the alcohol is properly added to form a water-alcohol mixture, so that the wetting capacity of the wetting agent can be reduced, and the technical process is more controllable. Alcohols commonly used as wetting agents are ethanol, propylene glycol, but ethanol is a flammable and explosive hazardous material and increases the cost of management when stored in a factory, and is safer than propylene glycol. Therefore, the invention selects the mixed solution of propylene glycol and water as the wetting agent.
Preferably, the rotation speed of the stirring knife is 100-500rpm, the rotation speed of the shearing knife is 600-1200rpm, the addition speed of the wetting agent is 5-20r/min, the atomization pressure is 0-0.1MPa, and the wet mixing time is 2-10min.
More preferably, the rotation speed of the stirring knife is 300rpm, the rotation speed of the shearing knife is 1000rpm, the adding speed of the wetting agent is 15r/min, the atomizing pressure is 0.01MPa, and the wet mixing time is 3min.
According to the invention, cefdinir, sucrose, dextrin, lactose, hydroxypropyl cellulose and silicon dioxide are preferably selected as the preparation composition of the cefdinir granules, and the stability, dissolution rate and compliance of the medicine are improved by means of the preparation.
Detailed Description
The invention discloses cefdinir granules and a preparation method thereof, and a person skilled in the art can use the contents for reference and properly improve process parameters for realization. It is specifically noted that all such substitutions and modifications will be apparent to those skilled in the art and are intended to be included herein. While the cefdinir granules of the present invention have been described in terms of preferred embodiments, it will be apparent to those of ordinary skill in the art that modifications, variations, and combinations of the cefdinir granules and the preparation method described herein can be made to implement and use the techniques of the present invention without departing from the spirit and scope of the invention.
All the cefdinir in the invention is C 14 H 13 N 5 O 5 S 2 And (6) counting. The invention is further illustrated by the following examples.
Example 1
The prescription process of the cefdinir granules is groped.
According to the results of the pre-prescription study in the previous period, a plurality of prescriptions are designed for comparison, and are specifically shown in table 1.
TABLE 1 prescription of cefdinir granules (unit is parts by mass)
Sieving the auxiliary materials with a 60-mesh sieve for later use, weighing cefdinir, sucrose, dextrin, lactose, hydroxypropyl cellulose and silicon dioxide according to the formula, fully mixing, placing in a wet granulation mixer, setting the rotating speeds of a stirring knife and a shearing knife to be 100rpm and 600rpm respectively, and opening for a period of time to uniformly mix the materials. Setting the rotation speeds of a stirring knife and a shearing knife to be 300rpm and 1000rpm respectively, using propylene glycol as a wetting agent, adjusting the rotation speed of a peristaltic pump to be 15r/min, adjusting the atomization pressure to be 0.01MPa, adding the wetting agent into the materials, preparing a soft material through high-speed shearing, carrying out wet mixing for 5min, and sieving with a 40-mesh sieve for wet granulation. And (3) putting the wet granules into a fluidized bed, and drying at 50 ℃ until the moisture is less than 2% to obtain dry granules. And (4) granulating the dry granules by using a 30-mesh sieve to obtain the cefdinir granules.
Table 2 product property examination results of cefdinir granules
In the formula, the sucrose, the dextrin and the HPC can excite viscosity after contacting water, wherein the sucrose is water-soluble and can generate larger viscosity, and the dosage of the sucrose is increased from R1 to R3, so that the granule forming is facilitated, the dissolution rate of the preparation can be improved, and the product is easy to absorb moisture; as can be seen from R5-R9, the influence of HPC of different models on the product properties is not very different, but the auxiliary material of the model HPC-L greatly increases the hygroscopicity, and the Carl index is greatly increased after the dosage of HPC is reduced, which means that the flowability is poor. From R10 and R11, siO is shown 2 There is no great difference in the effect on the flowability in the formulation range of 1-10%, but the water-insoluble SiO2 affects the dissolution rate of the granules when the amount is too large.
Through the research of the prescription, the preferable cefdinir granules comprise the following components: cefdinir, sucrose, dextrin, lactose, hydroxypropyl cellulose and silicon dioxide. By adopting the R3, the parameter range of the high-speed shearing wet granulation process is further explored.
TABLE 3 investigation results of high-speed shearing wet granulation process parameters and product properties
Within a certain range, the adding speed of the wetting agent and the rotating speed of the stirring knife have no obvious influence on various indexes, the flowability of the particles is slightly improved only along with the increase of the adding speed, and the dissolution rate of the particles is influenced when the rotating speed of the stirring knife is higher; the rotating speed of the shearing knife is reduced, so that the hygroscopicity of the granules is increased, the wet mixing time is increased, the hygroscopicity of the granules is reduced, the forming rate of the granules is slightly reduced due to the increase of the proportion of the propylene glycol in the wetting agent, and other indexes are not obviously influenced. The combination of parameters P2 is selected as more preferred.
Combining the R3 and the P2 to prepare a soft material, and sieving with a 40-mesh sieve for wet granulation. And (3) placing the wet granules in a fluidized bed, and drying at 50 ℃ air inlet temperature until the moisture is less than 2% to obtain dry granules. And (4) granulating the dry granules by using a 30-mesh sieve to obtain the cefdinir granules.
Example 2
Cefdinir granules
Prescription:
30 portions of cefdinir
44 parts of cane sugar
Dextrin 8 parts
Lactose 8 parts
HPC-SSL 7 parts
SiO 2 3 portions of
Sieving the auxiliary materials with a 60-mesh sieve for later use, weighing cefdinir, sucrose, dextrin, lactose, hydroxypropyl cellulose and silicon dioxide according to the formula, fully mixing, placing in a wet granulation mixer, setting the rotating speeds of a stirring knife and a shearing knife to be 100rpm and 600rpm respectively, and opening for a period of time to uniformly mix the materials. Setting the rotation speeds of a stirring knife and a shearing knife to be 300rpm and 1000rpm respectively, using about 54g of propylene glycol-water (70) as a wetting agent, adjusting the rotation speed of a peristaltic pump to be 10r/min, adjusting the atomization pressure to be 0.02MPa, adding the wetting agent into the materials, preparing a soft material through high-speed shearing, wherein the wet mixing time is 3min, and sieving with a 40-mesh sieve for wet granulation. And (3) placing the wet granules in a fluidized bed, and drying at 50 ℃ air inlet temperature until the moisture is less than 2% to obtain dry granules. And (4) finishing the dry granules by using a 30-mesh sieve to obtain the cefdinir granules.
Example 3
Cefdinir granules
Prescription:
20 portions of cefdinir
10 portions of cane sugar
Dextrin 20 parts
Lactose 40 portions
HPC-SSL 7 parts
SiO 2 3 portions of
Sieving the auxiliary materials with a 60-mesh sieve for later use, weighing cefdinir, sucrose, dextrin, lactose, hydroxypropyl cellulose and silicon dioxide according to the formula, fully mixing, placing in a wet granulation mixer, setting the rotation speeds of a stirring knife and a shearing knife to be 100rpm and 600rpm respectively, and opening for a period of time to uniformly mix the materials. Setting the rotation speeds of a stirring knife and a shearing knife to be 100rpm and 1200rpm respectively, using about 80g of propylene glycol-water (70) as a wetting agent, adjusting the rotation speed of a peristaltic pump to be 15r/min, adjusting the atomization pressure to be 0.01MPa, adding the wetting agent into the materials, preparing a soft material through high-speed shearing, wherein the wet mixing time is 5min, and sieving with a 40-mesh sieve for wet granulation. And (3) placing the wet granules in a fluidized bed, and drying at 50 ℃ air inlet temperature until the moisture is less than 2% to obtain dry granules. And (4) granulating the dry granules by using a 30-mesh sieve to obtain the cefdinir granules.
Stability studies were performed with the cefdinir particles of example 2.
1. Test for influencing factor
Cefdinir granules were prepared according to the recipe of example 2, and spread in a weighing bottle in a thin layer of about 5 mm thickness, and placed at 40 ℃ for 10 days as a high temperature environment, at 25 ℃ for 10 days as a high humidity environment under the condition of 90% +/-5% relative humidity, respectively, and placed at an illumination of 4500Lx for 10 days as a light environment, and sampled at 5 days and 10 days, and the properties, the drug content and the dissolution rate at 5min were measured, and the test results were compared with those on 0 day, and the results are shown in table 4.
TABLE 4 influence factor test results
Under high temperature conditions, the dry particles of example 2 were white and showed less change in content and dissolution rate than 0 day. In example 2, the appearance was changed from 0 day under high humidity, the particles were wet-soft and cohesive, and the color was lighter, but the content and dissolution rate were not significantly changed. Cefdinir should therefore be packaged in a moisture-proof manner and stored at room temperature. Under the condition of illumination, compared with 0 day, the appearance of the granule in the example 2 is changed, a small amount of brown substances are generated on the surface of the granule, and the content and the dissolution rate of the brown substances are obviously reduced. Indicating that cefdinir is unstable when exposed to light, cefdinir granules should be stored away from light.
2. Accelerated stability test
Cefdinir granules prepared according to the formulation of example 2, which simulated the packaging of commercial products, were stored for 6 months at 40 ℃ ± 2 ℃ and humidity of 75% ± 5%, and were sampled once at the end of 1 month, 3 months and 6 months during the test period, respectively, and the properties, moisture content, drug content, particle size distribution and 5min dissolution rate were examined, the results of which are shown in table 5.
TABLE 5 accelerated stability test results
From the above experimental results, it can be seen that the sample solution was left under accelerated conditions for 6 months, and the stability of the sample was good.
The foregoing is only a preferred embodiment of the present invention, and it should be noted that, for those skilled in the art, various modifications and decorations can be made without departing from the principle of the present invention, and these modifications and decorations should also be regarded as the protection scope of the present invention.
Claims (9)
1. A cefdinir granule, which is characterized in that: the raw materials comprise: cefdinir, sucrose, dextrin, lactose, hydroxypropyl cellulose and silicon dioxide.
2. Cefdinir granules according to claim 1, wherein: the raw materials comprise the following components in parts by weight: 5-30 parts of cefdinir, 40-80 parts of cane sugar, 5-20 parts of dextrin, 20-40 parts of lactose, 1-15 parts of hydroxypropyl cellulose and 1-10 parts of superfine silica gel powder.
3. Cefdinir granules according to claim 2, characterized in that: the raw materials comprise the following components in parts by weight: 20 parts of cefdinir, 50 parts of cane sugar, 10 parts of dextrin, 10 parts of lactose, 7 parts of hydroxypropyl cellulose and 3 parts of superfine silica gel powder.
4. Cefdinir granules according to any one of claims 1 to 3, wherein: the hydroxypropyl cellulose is selected from HPC-SSL, HPC-SL or HPC-L.
5. A method for preparing cefdinir granules according to any one of claims 1 to 3, wherein the method comprises the following steps: weighing cefdinir, sucrose, dextrin, lactose, hydroxypropyl cellulose and silicon dioxide, and placing the cefdinir, the sucrose, the dextrin, the lactose, the hydroxypropyl cellulose and the silicon dioxide in a wet granulation mixer to uniformly mix the materials; adjusting the rotation speed of a stirring knife and a shearing knife, setting the flow speed of a peristaltic pump and the atomization pressure, adding a wetting agent into the mixed material, preparing a soft material through high-speed shearing, and sieving, wetting and finishing granules; placing the wet granules in a fluidized bed, and drying until the moisture content is less than 2% to obtain dry granules; sieving and granulating the dry granules to obtain the cefdinir granules.
6. The method of claim 5, wherein: when the soft material is prepared, the rotating speed of the stirring knife is 100-500rpm, the rotating speed of the shearing knife is 600-1200rpm, the adding speed of the wetting agent is 5-20r/min, the atomizing pressure is 0-0.1MPa, and the wet mixing time is 2-10min.
7. The method of claim 6, wherein: the rotating speed of the stirring knife is 300rpm, the rotating speed of the shearing knife is 1000rpm, the adding speed of the wetting agent is 15r/min, the atomizing pressure is 0.01MPa, and the wet mixing time is 3min.
8. The production method according to claim 5, characterized in that: the wetting agent is propylene glycol and/or water.
9. The method for producing according to claim 7, characterized in that: the wetting agent is a mixed solution of propylene glycol and water, and the volume ratio of the propylene glycol to the water is 70:30.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202111072409.0A CN115804757A (en) | 2021-09-14 | 2021-09-14 | Cefdinir granules and preparation method thereof |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202111072409.0A CN115804757A (en) | 2021-09-14 | 2021-09-14 | Cefdinir granules and preparation method thereof |
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| Publication Number | Publication Date |
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| CN115804757A true CN115804757A (en) | 2023-03-17 |
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| CN202111072409.0A Pending CN115804757A (en) | 2021-09-14 | 2021-09-14 | Cefdinir granules and preparation method thereof |
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- 2021-09-14 CN CN202111072409.0A patent/CN115804757A/en active Pending
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