CN110613697A

CN110613697A - Cefalexin capsule and preparation method thereof

Info

Publication number: CN110613697A
Application number: CN201911041693.8A
Authority: CN
Inventors: 孙佳欣; 黄玉芬; 王立华
Original assignee: Chuangchun Dirui Pharmaceutical Co Ltd
Current assignee: Chuangchun Dirui Pharmaceutical Co Ltd
Priority date: 2019-10-30
Filing date: 2019-10-30
Publication date: 2019-12-27

Abstract

The invention discloses a cefalexin capsule and a preparation method thereof, the cefalexin capsule comprises 90.6 percent of cefalexin, 6.4 to 8.3 percent of microcrystalline cellulose, 0.6 to 1.6 percent of sodium carboxymethyl cellulose and 0.5 to 1.4 percent of magnesium stearate, and the sum of the weight percentages of the components is 100 percent; the preparation process of the capsule comprises the following steps: premixing at 10Hz frequency for 16min, granulating, batch mixing at 10Hz frequency for 10min, and filling into capsule; the granulation conditions were: stirring speed 25rpm, screw rotation speed 55-85rpm, compression roller rotation speed 16rpm, compression roller gap 0.9-1.3mm, whole granule rotation speed 80rpm, compression roller pressure 100-; the capsule of the invention has improved fluidity and dissolution stability, and the method for preparing the capsule has low energy consumption and is green and environment-friendly.

Description

Cefalexin capsule and preparation method thereof

Technical Field

The invention belongs to the technical field of pharmaceutical preparations, and relates to a cefalexin capsule and a preparation method thereof.

Background

Bacterial infection is the most common and frequent infectious diseases and complications clinically, harms human health, and treatment means mainly depends on antibiotic medicines. The cefalexin is the first generation oral cephalosporin antibiotics, and is mainly clinically applicable to respiratory tract infection, urinary tract infection, skin soft tissue infection and the like caused by sensitive bacteria in China, such as acute tonsillitis, angina, bronchitis, pneumonia and the like. Cefalexin (Cefalexin, i.e. cephalosporin IV) is beta-lactam antibiotic, and cell contents are expanded to be broken and dissolved by inhibiting the synthesis of cell walls, so that the bactericidal effect is achieved.

Cephalexin is an oral cephalosporin antibiotic developed by the american research institute in 1967, and cephalexin capsules produced by ShionogiInc (american salt wild-type pharmaceuticals) were first approved by japan salt wild-type pharmaceuticals corporation in 1970 and 04 in japan and 1 in 1971, and approved by the U.S. food and drug administration. Currently, cefalexin preparations on the market at home mainly comprise tablets, granules, capsules, dry suspensions and the like, and three hundred enterprises at home are approved to produce cefalexin capsule preparations.

The cefalexin capsule comprises cefalexin, magnesium stearate and corn starch. Starch has the characteristics of poor adhesiveness, compressibility, flowability and the like, and is often unstable in dissolution in the actual production process, so that the product quality is influenced.

At present, the preparation process of the variety mainly comprises the steps of directly filling capsules after mixing raw materials and auxiliary materials and filling capsules after wet granulation or dry granulation.

The cefalexin raw material has low bulk density and fluffy material, and if the powder is directly filled into capsules after being mixed, the flowability is poor and the dissolution is unstable, so that the product quality is unstable; in the actual production, the product prepared by wet granulation is not only unstable in dissolution, but also small in bulk density of the prepared granules, so that the volume of the content is large and cannot reach the volume limit of the content in a given capsule, and the quality of the product is unstable; the literature "technological improvement of cephalexin capsules _: the prescription is 1000 prepared from 125g of cefalexin capsules, a proper amount of Starch1500, 2 percent of aerosil and 1 percent of magnesium stearate; the process comprises the steps of uniformly mixing fine cefalexin raw material powder, Starch1500 and aerosil in a mixer, then pressing the mixture into slices with proper hardness and thickness in a dry type granulator, then grinding the slices through a sieve with 24 holes/25.4 mm, mixing the obtained granules with magnesium stearate, and filling the mixture into capsules.

Disclosure of Invention

In order to achieve the aim, the invention provides a cefalexin capsule, which solves the problems of unstable dissolution and poor product fluidity of the cefalexin capsule in the prior art.

The invention also aims to provide a preparation method of the cefalexin capsule.

In order to solve the technical problems, the invention adopts the technical scheme that the cefalexin capsule comprises the following components in percentage by weight: 90.6 percent of cefalexin, 6.4 to 8.3 percent of diluent, 0.6 to 1.6 percent of adhesive and 0.5 to 1.4 percent of lubricant, wherein the total amount of all the components is 100 percent;

the diluent is selected from one of microcrystalline cellulose, dextrin and sorbitol;

the adhesive is selected from one of sodium carboxymethylcellulose, methylcellulose and hydroxypropyl cellulose;

the lubricant is selected from one of magnesium stearate, calcium stearate, stearic acid and talcum powder.

Further, the diluent is preferably microcrystalline cellulose.

Further, the binder is preferably sodium carboxymethylcellulose.

Further, the lubricant is preferably magnesium stearate.

Further, the capsule comprises the following components in percentage by weight: 90.6% of cefalexin, 7.9% of microcrystalline cellulose, 1.0% of sodium carboxymethyl cellulose and 0.5% of magnesium stearate.

The invention adopts another technical scheme that a preparation method of cefalexin capsules comprises the following steps:

step S1, premixing: adding cefalexin, a diluent and an adhesive into a three-dimensional motion mixer, setting the frequency of the three-dimensional motion mixer to be 10Hz, and mixing for 16 min;

step S2, pelletization: adding the mixed medicinal powder into a dry granulating machine for dry granulation;

step S3, batch mixing: adding the above granules and lubricant into a three-dimensional motion mixer, and mixing at frequency of 10Hz for 10 min;

step S4, capsule filling: and putting the mixed powder into a capsule filling machine to fill capsules.

Further, the diluent in step S1 is microcrystalline cellulose, and the binder is sodium carboxymethylcellulose.

Further, in step S2, the lubricant is magnesium stearate.

Further, the parameters of the granulator in the step S2 are: the stirring speed is 25rpm, the screw rotating speed is 55-85rpm, the press roll rotating speed is 16rpm, the press roll gap is 0.9-1.3mm, the whole grain rotating speed is 80rpm, the press roll pressure is 100-130bar, the whole grain sieve pore size is 1.0mm, and the vacuum degree is 0.1 bar.

Wherein, the spiral rotating speed of 55-85rpm, the compression roller gap of 0.9-1.3mm and the working pressure of 100-130bar can affect the feeding continuity, the tabletting thickness, the granule hardness and the like of the product, which leads to excessive powder in the granule curing process, unstable dissolution and further affects the product quality.

Microcrystalline cellulose is preferably selected in the diluent, the diluent can be used for wet granulation and dry granulation, has a certain flow aiding and anti-caking effect, is high in flowability, is not absorbed after the microcrystalline cellulose is taken orally, almost has no potential toxicity, and other types of diluents are relatively poor in compressibility and flowability, so that the product is not dissolved stably, and the product quality is influenced. The adhesive is preferably sodium carboxymethylcellulose, is not only suitable for wet granulation but also suitable for dry granulation, can be used as a dry adhesive, has strong adhesive force, and other types of adhesives have relatively poor compressibility and flowability, and can cause unstable dissolution of a product, thereby affecting the quality of the product. The lubricant is preferably magnesium stearate which has strong lubricating property, good viscosity resistance, light weight, adsorption property, easy mixing with particles, good adhesive force and difficult separation, and other types of diluents have poor adhesive force relatively, and can be separated from the particles due to mechanical vibration in the production process, so that the lubricating effect is reduced.

The compatibility of the raw materials and the auxiliary materials is researched aiming at the preferable auxiliary materials, and the following table shows that:

TABLE 1 compatibility test results of raw and auxiliary materials

Note: blank auxiliary materials are microcrystalline cellulose: sodium carboxymethylcellulose: magnesium stearate is prepared by mixing the following raw materials in percentage by weight: 2: 1, and mixing.

The experimental results of compatibility of the raw materials and the auxiliary materials show that the raw materials and the auxiliary materials are stable after being mixed under the condition of compatibility of the raw materials and the auxiliary materials and have properties similar to those of the raw materials, so that the optimal auxiliary materials are determined to be used for developing and researching the process formula.

The selection basis of auxiliary material types is as follows: the cefalexin capsule comprises cefalexin, magnesium stearate and corn starch. The compressibility and fluidity of corn starch are poor, so the invention discloses a formula, and microcrystalline cellulose with stronger fluidity is selected to replace the corn starch. Because the preparation process disclosed by the invention is dry granulation, the dry adhesive sodium carboxymethylcellulose with stronger adhesive force is selected. The magnesium stearate has strong lubricating property, light weight and adsorption property, and is easy to be uniformly mixed with particles, so the magnesium stearate is used as the lubricating agent.

Selecting the dosage of auxiliary materials: the sodium carboxymethylcellulose is used as a binder, the general dosage is 1.0-6.0%, the dosage of magnesium stearate is 0.25-5.0%, and the magnesium stearate can influence the dissolution, so that the screening is started from a lower concentration of about 0.5%; microcrystalline cellulose is used as a diluent, and the addition amount is controlled by the weight of the content; thus, prescription screening studies are carried out. The sodium carboxymethylcellulose is used as a binder in the product, the common dosage of the binder is 1.0-6.0%, and the dosage of the binder influences the dissolution, but the invention discovers that when the dosage of the binder is 0.6%, the dosage of the binder is lower than the lowest value of the common dosage, but the material dosage is saved under the dosage range, and the dissolution meets the requirement (the dissolution in 15min is more than 85%), so that the dosage of the sodium carboxymethylcellulose is determined to be 0.6-1.6%. Magnesium stearate is generally used in an amount of 0.25 to 5.0% as a lubricant, and when the amount is too large, since dissolution is retarded due to hydrophobicity, the screening is started from a low concentration of about 0.5%, and the results show that: when the magnesium stearate is used in an amount of 0.5-1.4%, the dissolution is stable, the flowability of the product is good, when the magnesium stearate is used in an excessive amount, the dissolution of the product may tend to be reduced during scale-up, and when the magnesium stearate is used in an excessive amount, the flowability of the product may be affected, so that the magnesium stearate is determined to be used in an amount of 0.5-1.4%.

The invention has the beneficial effects that:

based on the components proportion of the cefalexin capsule, the problems of flowability and unstable dissolution of the cefalexin capsule can be solved, and the product quality can be ensured. The cefalexin capsule prepared by the invention is filled after dry granulation is selected, and the parameters of the preparation method are limited, so that the flowability of the granulated material is obviously improved; the product is dissolved stably, and the product quality can be ensured; the dry granulation is continuous production equipment, the productivity is easy to expand, the energy consumption is low, and the method is more environment-friendly. In the preparation method, the problems of fluidity and unstable dissolution are solved by adding auxiliary materials and granulating, so that the requirement of filling capsules is met, and the stable quality of products is ensured.

Detailed Description

The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.

Example 1

A preparation method of cefalexin capsules comprises the following steps:

step S1, premixing: adding 90.6% of cefalexin, 7.9% of microcrystalline cellulose and 1.0% of sodium carboxymethylcellulose (weight percentage in the embodiment) into a three-dimensional motion mixer, setting the frequency of the three-dimensional motion mixer to be 10Hz, and mixing for 16 min;

step S2, pelletization: adding the mixed medicinal powder into a dry granulating machine for dry granulation; the parameters of the granulator are as follows: stirring speed 25rpm, screw rotation speed 80rpm, compression roller rotation speed 16rpm, compression roller gap 1.1mm, whole grain rotation speed 80rpm, compression roller pressure 120bar, whole grain sieve mesh aperture 1.0mm, and vacuum degree 0.1 bar;

step S3, batch mixing: adding the above granules and 0.5% magnesium stearate into three-dimensional motion mixer, and mixing at frequency of 10Hz for 10 min;

Example 2

Microcrystalline cellulose in step S1 of example 1 was replaced with dextrin, sodium carboxymethylcellulose was replaced with methylcellulose, magnesium stearate in step S3 was replaced with stearic acid, and the rest were unchanged.

Example 3

Microcrystalline cellulose in step S1 of example 1 was replaced with sorbitol, sodium carboxymethylcellulose was replaced with hydroxypropyl cellulose, magnesium stearate in step S3 was replaced with talc, and the rest were unchanged.

Example 4

A preparation method of cefalexin capsules comprises the following steps:

step S1, premixing: adding 90.6% of cefalexin, 8.3% of microcrystalline cellulose and 0.6% of sodium carboxymethylcellulose (weight percentage in the embodiment) into a three-dimensional motion mixer, setting the frequency of the three-dimensional motion mixer to be 10Hz, and mixing for 16 min;

step S2, pelletization: adding the mixed medicinal powder into a dry granulating machine for dry granulation; the parameters of the granulator are as follows: stirring speed 25rpm, screw rotation speed 85rpm, compression roller rotation speed 16rpm, compression roller gap 1.3mm, whole grain rotation speed 80rpm, compression roller pressure 130bar, whole grain sieve mesh aperture 1.0mm, and vacuum degree 0.1 bar;

Example 5

A preparation method of cefalexin capsules comprises the following steps:

step S1, premixing: adding 90.6% of cefalexin, 6.4% of microcrystalline cellulose and 1.6% of sodium carboxymethylcellulose (weight percentage in the embodiment) into a three-dimensional motion mixer, setting the frequency of the three-dimensional motion mixer to be 10Hz, and mixing for 16 min;

step S2, pelletization: adding the mixed medicinal powder into a dry granulating machine for dry granulation; the parameters of the granulator are as follows: stirring speed 25rpm, screw rotation speed 55rpm, compression roller rotation speed 16rpm, compression roller gap 0.9mm, whole grain rotation speed 80rpm, compression roller pressure 100bar, whole grain sieve mesh aperture 1.0mm, and vacuum degree 0.1 bar;

step S3, batch mixing: adding the above granules and 1.4% magnesium stearate into three-dimensional motion mixer, and mixing at frequency of 10Hz for 10 min;

Example 6

A preparation method of cefalexin capsules comprises the following steps:

step S1, premixing: adding 90.6% of cefalexin, 5.4% of microcrystalline cellulose and 2.1% of sodium carboxymethylcellulose (weight percentage in the embodiment) into a three-dimensional motion mixer, setting the frequency of the three-dimensional motion mixer to be 10Hz, and mixing for 16 min;

step S2, pelletization: adding the mixed medicinal powder into a dry granulating machine for dry granulation; the parameters of the granulator are as follows: stirring speed 25rpm, screw rotation speed 90rpm, compression roller rotation speed 16rpm, compression roller gap 1.5mm, whole grain rotation speed 80rpm, compression roller pressure 140bar, whole grain sieve mesh aperture 1.0mm, and vacuum degree 0.1 bar;

step S3, batch mixing: adding the above granules and 1.9% magnesium stearate into three-dimensional motion mixer, and mixing at frequency of 10Hz for 10 min;

Example 7

A preparation method of cefalexin capsules comprises the following steps:

step S1, premixing: adding 90.6% of cefalexin, 9% of microcrystalline cellulose and 0.2% of sodium carboxymethylcellulose (weight percentage in the embodiment) into a three-dimensional motion mixer, setting the frequency of the three-dimensional motion mixer to be 10Hz, and mixing for 16 min;

step S2, pelletization: adding the mixed medicinal powder into a dry granulating machine for dry granulation; the parameters of the granulator are as follows: stirring speed 25rpm, screw rotation speed 50rpm, compression roller rotation speed 16rpm, compression roller gap 0.7mm, whole grain rotation speed 80rpm, compression roller pressure 90bar, whole grain sieve mesh aperture 1.0mm, and vacuum degree 0.1 bar;

step S3, batch mixing: adding the above granules and 0.2% magnesium stearate into three-dimensional motion mixer, and mixing at frequency of 10Hz for 10 min;

The powders of the products of the above 7 groups of examples and the dissolution results are shown in tables 2 and 3:

table 2 product powder results table of examples

Examples	No. 5 sub-sieve powder (%)
		Example 1	30
Example 2	42
		Example 3	47
Example 4	34
		Example 5	38
Example 6	49
		Example 7	50

Table 3 dissolution results of the products of the examples

As can be seen from the results of tables 2 and 3, the powder under the sieves of examples 1 and 5 is 30% which is far below the general specification (less than or equal to 40%); the dissolution RSD value (relative standard deviation value) at each time point is far lower than the general regulation (5 min: RSD percent is less than or equal to 20 percent, 10min and later RSD percent is less than or equal to 10 percent), the dissolution rate at 15min is 94.8 percent, and the dissolution rate is much higher than the standard regulation (85 percent). The powder below the No. 5 sieve of the embodiment 2 and the embodiment 3 is more than that of the powder below the No. 5 sieve, and slightly exceeds the standard specification (less than or equal to 40 percent); the 15min dissolution rate is 85.4 percent and 86.1 percent respectively, which just reach the standard requirement (85 percent), but the RSD value at 5min exceeds the general specification (RSD percent is less than or equal to 20 percent), which indicates that the dissolution rate of the product is unstable. ③ the powders below the sieves of the embodiment 4, the embodiment 5 and the embodiment 5 meet the general regulations (less than or equal to 40 percent), the dissolution RSD value at each time point meets the general regulations (5 min: RSD percent is less than or equal to 20 percent, 10min and later RSD percent is less than or equal to 10 percent), and the dissolution rate at 15min is higher than the standard regulations (85 percent). The powders below the sieves of example 6, example 7 and No. 5 are all more than the general specification (less than or equal to 40 percent); the RSD% value of the dissolution within 30min meets the general regulation (RSD% is less than or equal to 10%), the RSD% values of other time points exceed the general regulation, and the dissolution within 15min does not meet the standard regulation (85%).

In combination with the above analysis, only example 1, example 4 and example 5 were in compliance with the regulations, and example 1 was the most preferable.

The preparation process of the cefalexin capsule of the invention is described as follows:

(1) screening of preparation Process

The study uses the same prescription (i.e. the prescription in example 1) to carry out the process preparation through wet granulation and dry granulation respectively, and the bulk density and the dissolution condition are examined, so that the dissolution rate of the wet granulation for 15min is 52.8%, and the f2 (similar factor) is 22; the dry granulation has a dissolution of 87.1%, a 15min dissolution of greater than 85%, and f2 of 60, consistent with the provision of a 15min dissolution of greater than 85%, and f2 of greater than 50, and the dry granulation has a greater bulk density than the wet granulation, thereby reducing the volume of the contents.

Table 4 comparative table of screening research results of preparation process

The invention provides a cefalexin capsule and a preparation method thereof, the prescription is completely different from the literature of' process improvement of cefalexin capsule _.

(2) Premixing:

the purpose of the premixing process is to uniformly mix materials and reduce the risk of nonuniform preparation content. According to the invention, research and investigation are carried out on the premixing time and the mixing frequency, and finally the mixing time is determined to be 16min and the mixing frequency is determined to be 10 Hz.

Table 5 mixing time screening

As is clear from the results in Table 5, the mixing time of 5min is not satisfactory because not only the highest value of 89.81% is out of the acceptable range of 81.0% to 89.6%, but also the RSD value of 2.31% is out of the acceptable range of 2.0%. The mix 8min and mix 16min levels and RSD values were within acceptable ranges, but in comparison, the mix 16 minsrd value of 0.92% was less, indicating more uniform mixing of the materials, thus determining the optimum mixing time to be 16 min. Sampling 9 samples, namely taking nine points to measure the mixing uniformity when premixing for 5min, 8min and 16min respectively.

Table 6 mixing frequency screening:

from the results in table 6, it can be seen that the content uniformity RSD at the mixing frequency of 8Hz is 0.92%, which is much larger than the RSD values at the mixing frequencies of 10Hz and 15Hz, and the average content and RSD values at the mixing frequencies of 10Hz and 15Hz are not much different, but considering that the higher the frequency is, the more the wear of the machine equipment is, the smaller the mixing frequency is, the 10Hz is selected finally. Sampling 9 samples, namely taking nine points under different mixing frequencies respectively after premixing, and measuring the mixing uniformity.

(3) Granulating

The purpose of the granulation is: the fluidity of the material is increased, the bulk density of the medicine is increased, the material is made into particles with certain density and fluidity, the dissolution rate is improved, and the product quality is ensured.

Pressure and screen pore size screening: the pressure of the equipment and the whole grain screen are main influencing factors of dry granulation, and the combination of the pressure and the whole grain screen influences the flowability and the dissolution of the granules, so that the pressure of the press roll and the aperture of the screen mesh are considered, and the results are as follows:

TABLE 7 pressure and Screen Aperture Sieve Table

Note: dissolution conditions: basket method, 50rpm, pH4.5 acetate buffer.

The results show that: at the same screen mesh size, 120bar pressure dissolution was faster than 80bar pressure dissolution, and at the same pressure, 1.0mm screen dissolved slightly faster than 0.8mm screen. The bulk density difference is not great. When the pressure is 120bar and the aperture of the screen mesh is 1.0mm, the angle of repose is the smallest, and the fluidity is the best. Therefore, the optimal combination of pressure of 120bar (the feasible interval is 100-130 bar) and the screen pore diameter of 1.0mm is determined.

Besides the pressure of the press roll and the aperture of the screen mesh, the spiral rotating speed, the rotating speed of the press roll and the clearance between the press rolls have great influence on the dissolution and the fluidity in the granulation process, so the invention also researches and investigates the dissolution and the fluidity, and the results are as follows:

TABLE 8 SCREENING TABLE FOR SCREW ROTATION SPEED, PRESS-ROLLER INTERVAL

From the results in table 8, it can be seen that under the combined conditions of the same roll pressure and the same screen mesh diameter, the roll rotation speed of 16rpm, the roll gap of 1.1mm (the feasible region of 0.9-1.3 mm), and the screw rotation speed of 80rpm (the feasible region of 55-85 rpm), the dissolution effect is the best, and in the particle size distribution investigation, the fine powder is the least, indicating that the fluidity is the best; therefore, the rotating speed of the compression roller is 16rpm, the gap between the compression rollers is 1.1mm (the feasible interval is 0.9-1.3 mm), and the screw rotating speed is 80rpm (the feasible interval is 55-85 rpm).

(4) Batch mixing: aims to increase the lubricity of the materials and improve the fluidity to facilitate the filling of the capsules.

The capsule prepared by the invention is a preparation with a large proportion of raw material medicine (cefalexin), the particle uniformity is good after premixing and granulation, the invention screens the mixing time by taking the mixing uniformity as an index, and finally determines the mixing time to be 10 min.

TABLE 9 batch mixing time screening

As is clear from the results in Table 9, the mixing uniformity was not significantly different among the mixtures of 10min, 15min and 20min, and the minimum mixing time was selected to be 10 min. In table 9, batch mixing refers to mixing the granules prepared in step S2 with magnesium stearate as lubricant, and nine points are taken at 10min, 15min and 20min respectively during mixing for detecting the mixing uniformity.

(5) And (3) filling capsules: and (4) feeding the particles after batch mixing into a capsule filling machine for capsule filling.

According to the screening optimal production process (example 1), 3 batches of products are respectively produced, the optimality of the product prescription and the preparation method is further verified, stability investigation research is carried out, the dissolution and cefalexin contents of the 3 batches of products are stable, the contents are much higher than the conventional values (93%), and the product quality is ensured. Wherein the contents in tables 5-6 and tables 9-11 refer to cephalexin contents. Capsules were prepared as in example 1, 48 million capsules were prepared per batch, and 3 batches of capsules were prepared, and since long term and accelerated stability were checked after the pack and the finished product was set out, 480 capsules were randomly extracted per batch and filled into 20 boxes for accelerated stability testing, and 960 capsules were randomly extracted per batch and filled into 40 boxes for long term stability testing.

TABLE 10 accelerated stability content test data

TABLE 11 Long term stability data

The advantages of the dry granulation process over wet granulation are: (1) the fluidity and the dissolution stability of the granulated material are obviously improved; (2) the dry granulation is continuous production equipment, the productivity is easy to expand, the energy consumption is lower than that of the wet granulation, and the method is more environment-friendly. (3) Compared with wet granulation, dry granulation can reduce the volume of the content and meet the requirement of the limit of the given capsule.

Clinical trials were conducted on the basis of the examples, and the drug of example 1 was selected as the formulation of the present invention.

And (3) clinical trials:

1. case selection

96 respiratory tract infection patients, 49 men and 47 women, age 18-60 years, average age 47.8 years, clinical signs and experimental bacterial culture prove that the respiratory tract infection is bacterial.

2. Method of administration

The cefalexin capsule developed according to the embodiment 1 of the invention is 0.5g for each time, 4 times per day, one treatment course is 7 days, and 1-2 treatment courses are treated without other antibiotics.

The judgment standard of the curative effect is as follows: the four grades of cure, obvious effect, progress and no effect are evaluated.

The recovery is that the body temperature is normal, the clinical symptoms disappear, and the test results, X-rays and other auxiliary examination indexes are normal.

Has obvious effects that the body temperature is normal, clinical symptoms basically disappear, and test results, X-rays and other auxiliary examination indexes are basically normal.

The improvement of body temperature reduction but not normal, clinical symptoms improvement, and improvement of test results, X-ray and other auxiliary examination indexes.

The clinical symptoms are not improved, and the test results, X-rays and other auxiliary examination indexes are not improved.

The healing and the obvious effect are calculated to be effective, and the total effective rate is calculated according to the effective rate. The results are as follows:

TABLE 12 statistics of treatment efficacy

Disease species	Number of examples	Recovery method	Show effect	Progress of the technology	Invalidation
						Acute bronchitis	31	26	4	1	0
Acute laryngopharyngitis	19	13	5	1	0
						Acute tonsillitis	36	32	3	1	0
Acute episode of chronic bronchitis	10	7	2	0	1
						Total up to	96	78	14	3	1

The cure rate of 96 patients after 1-2 courses of treatment is 81.3%, the significant efficiency is 14.6%, and the total effective rate is 95.8%.

58 pathogenic bacteria strains are separated out in a laboratory, and after treatment, the pathogenic bacteria strains turn negative 52 strains, and the negative turning rate is 89.7 percent.

TABLE 13 pathogen eradication protocol

Pathogenic bacteria	Number of plants	Transgenic plant of negative
			Pneumococcus	11	10
Staphylococcus aureus	19	18
			Proteus mirabilis	4	3
Haemophilus influenzae	6	4
			Group D streptococci	6	6
Staphylococcus epidermidis	12	11
			Total up to	58	52

To summarize: 96 patients with respiratory tract infection have the cure rate of 81.3 percent, the significant efficiency of 14.6 percent and the total effective rate of 95.8 percent,

the negative conversion rate of the bacteria is 89.7 percent, the effect is obvious, and no adverse reaction and toxic or side effect are found, so that the pharmaceutical composition is worthy of being popularized in the treatment of respiratory tract infection.

The above description is only for the preferred embodiment of the present invention, and is not intended to limit the scope of the present invention. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention shall fall within the protection scope of the present invention.

Claims

1. The cefalexin capsule is characterized by comprising the following components in percentage by weight: 90.6 percent of cefalexin, 6.4 to 8.3 percent of diluent, 0.6 to 1.6 percent of adhesive and 0.5 to 1.4 percent of lubricant, wherein the total amount of all the components is 100 percent;

2. Cefalexin capsule according to claim 1, wherein the diluent is microcrystalline cellulose.

3. Cefalexin capsule according to claim 1, wherein the binder is sodium carboxymethylcellulose.

4. Cefalexin capsule according to claim 1, wherein the lubricant is magnesium stearate.

5. Cefalexin capsule according to any one of claims 1 to 4, characterised in that it comprises the following components in percentage by weight: 90.6% of cefalexin, 7.9% of microcrystalline cellulose, 1.0% of sodium carboxymethyl cellulose and 0.5% of magnesium stearate.

6. A process for the preparation of cefalexin capsules according to claim 1, comprising:

step S3, batch mixing: adding the above granules and lubricant into three-dimensional motion mixer, mixing at frequency of 10HZ for 10 min;

7. The process according to claim 6, wherein the diluent in step S1 is microcrystalline cellulose and the binder is sodium carboxymethylcellulose.

8. The process according to claim 6, wherein the lubricant in step S2 is magnesium stearate.

9. The process according to claim 6, wherein the parameters of the granulator in step S2 are: the stirring speed is 25rpm, the screw rotating speed is 55-85rpm, the press roll rotating speed is 16rpm, the press roll gap is 0.9-1.3mm, the whole grain rotating speed is 80rpm, the press roll pressure is 100-130bar, the whole grain sieve pore size is 1.0mm, and the vacuum degree is 0.1 bar.