CN115444824B

CN115444824B - Cefprozil composition and application thereof

Info

Publication number: CN115444824B
Application number: CN202211268730.0A
Authority: CN
Inventors: 宋珊珊; 高春花; 张艺峰; 陈达红; 郑琪耀
Original assignee: Shenzhen Lijian Pharmaceutical Co ltd
Current assignee: Shenzhen Lijian Pharmaceutical Co ltd
Priority date: 2022-10-17
Filing date: 2022-10-17
Publication date: 2023-06-09
Anticipated expiration: 2042-10-17
Also published as: CN115444824A

Abstract

The invention discloses a cefprozil composition and application thereof, and belongs to the technical field of medicine preparation. The cefprozil composition comprises the following raw materials in parts by weight: 12-14 parts of cefprozil, 50-60 parts of sucrose, 25-35 parts of mannitol, 0.1-0.7 part of sodium carboxymethyl cellulose, 0.3-0.8 part of colloidal silicon dioxide and 0.2-0.7 part of sodium chloride. The composition disclosed by the invention is simple in components, and the components are matched with each other, so that the dissolution effect and the uniform stability of the cefprozil dry suspension can be effectively ensured.

Description

Cefprozil composition and application thereof

Technical Field

The invention relates to the technical field of medicine preparation, in particular to a cefprozil composition and application thereof.

Background

Cefprozil is (6R, 7R) -3-propenyl-7- [ (R) -2-amino-2- (4-hydroxyphenyl) acetamido ] -8-oxo-5-thia-1-azabicyclo [4.2.0] oct-2-ene-2-carboxylic acid-hydrate, belonging to beta-lactam antibiotics. The action mechanism of the antibacterial agent is similar to that of other cephalosporins, the antibacterial agent mainly plays an antibacterial role by blocking bacterial cell wall biosynthesis, and the antibacterial agent has stronger activity against gram-negative bacillus and stability against gram-negative bacillus beta-lactamase than the first-generation cephalosporins, so that the antibacterial agent has good application prospect.

The cefprozil is prepared into a dry suspension, so that the dry suspension is convenient to carry, good in stability and convenient to take; however, the instant dry suspension is required to be rapidly dissolved and also required to have proper physical stability, so how to select proper auxiliary materials to ensure the dissolution effect and uniform stability of the cefprozil dry suspension is a technical problem to be solved by the technicians in the field.

Disclosure of Invention

In view of the above, the invention provides a cefprozil composition, which is applied to the preparation of cefprozil dry suspension, and can ensure the dissolution effect and uniform stability of the cefprozil dry suspension.

In order to achieve the above purpose, the present invention adopts the following technical scheme:

the cefprozil composition comprises the following raw materials in parts by weight:

12-14 parts of cefprozil,

50-60 parts of sucrose and the balance of the total weight of the mixture,

25-35 parts of mannitol and the like,

0.1 to 0.7 part of sodium carboxymethyl cellulose,

0.3 to 0.8 parts of colloidal silica,

sodium chloride 0.2-0.7 parts.

The cefprozil, the sucrose, the mannitol, the sodium carboxymethyl cellulose, the colloidal silicon dioxide and the sodium chloride are compounded according to a specific proportion, so that the uniform stability after granulation is good, the drug dissolution speed is high, and the bioavailability is improved.

Preferably, the composition further comprises the following raw materials in parts by weight:

0.1 to 0.5 part of aspartame,

0.1-0.2 part of essence.

microcrystalline cellulose 0.2-0.5 parts.

The cefprozil composition can be used for preparing a cefprozil pharmaceutical preparation, and pharmaceutically acceptable auxiliary materials are added into the cefprozil composition to prepare the pharmaceutical preparation.

Preferably, the pharmaceutical formulation comprises a dry suspension.

A cefprozil dry suspension, which comprises the cefprozil composition.

The preparation method of the cefprozil dry suspension comprises the following steps:

(1) Mixing cefprozil, sucrose, mannitol, sodium carboxymethyl cellulose, colloidal silicon dioxide and sodium chloride to prepare a premix;

(2) Adding water into the premix to prepare a soft material, and preparing the soft material into wet particles; adding a proper amount of purified water according to the wetting condition, wherein the average dosage of the purified water to a single dosage is 25-55 mu L;

(3) The wet granules are dried.

Preferably, in the step (3), the wet granules are dried at a drying temperature of 40-50 ℃ until the moisture is less than or equal to 3%.

Preferably, in the step (3), the aspartame and the essence are added after the wet particles are dried, and the wet particles are uniformly mixed.

Preferably microcrystalline cellulose is also added when preparing the premix.

In conclusion, the composition disclosed by the invention is simple in components, and the components are matched with each other, so that the dissolution effect and the uniform stability of the cefprozil dry suspension can be effectively ensured.

Drawings

FIG. 1 shows the dissolution test results of prescription 1 of example 3;

FIG. 2 shows the dissolution test results of prescription 2 of example 3;

FIG. 3 shows the dissolution test results for formulation 3 of example 3;

FIG. 4 shows the dissolution test results for formulation 4 of example 3;

FIG. 5 shows the dissolution test results for formulation 5 of example 3;

FIG. 6 shows the dissolution test results for formulation 6 of example 3;

FIG. 7 shows the dissolution test results for formulation 7 of example 3;

FIG. 8 shows the result of dissolution test of prescription 8 of example 3.

Detailed Description

Example 1

The preparation method of the cefprozil dry suspension according to the prescription of the table 1 comprises the following steps:

(1) Cefprozil, sucrose, mannitol, sodium carboxymethyl cellulose, colloidal silica and sodium chloride are mixed to obtain a premix.

(2) Adding purified water into the premix to prepare a soft material, adding a proper amount of purified water according to the wetting condition, averaging to the dosage of 25-55 mu L of single dose, preparing wet particles, and drying and granulating to obtain the finished product.

TABLE 1

Raw material name	Prescription 1 (mg)	Prescription 2 (mg)	Prescription 3 (mg)
				Cefprozil	125	125	125
Sucrose	500	550	560
				Mannitol (mannitol)	350	300	280
Sodium carboxymethyl cellulose	5	5	5
				Colloidal silica	5	5	5
Sodium chloride	4	4	4

The formulations 1, 2 and 3 all succeeded in preparing the granules. Adding the prepared particles of each prescription into purified water, shaking for about 1 minute, standing and observing the cup bottom, and the results show that the cup bottom has a little sediment after the prescriptions 1 and 2 stand still, the solution suspension state of the prescription 3 is good, and the cup bottom has no sediment. Therefore, when the amounts of sucrose and mannitol are adjusted, the sucrose addition ratio should be increased and the mannitol addition ratio should be decreased.

Example 2

Cefprozil dry suspension was prepared according to the recipe in table 2.

TABLE 2

Raw material name	Prescription 1 (mg)	Prescription 2 (mg)
			Cefprozil	125	125
Sucrose	555	555
			Mannitol (mannitol)	280	280
Sodium carboxymethyl cellulose	0.75	7
			Colloidal silica	5	5
Sodium chloride	4	4
			Aspartame	2.5	2.5
Mixed fruit powder essence	1	1
			Strawberry powder essence	1	1

Wherein, the preparation method of the prescription 1 is as follows:

(1) Cefprozil, sucrose, mannitol, colloidal silica, sodium chloride are mixed into a premix.

(2) Adding sodium carboxymethylcellulose into purified water, and stirring thoroughly to obtain sodium carboxymethylcellulose solution with mass fraction of 1%.

(3) Adding sodium carboxymethyl cellulose solution into the premix to prepare soft material, granulating with 14 meshes, drying, and finishing with 12 meshes.

(4) Adding aspartame, mixed fruit powder essence and strawberry powder essence into the obtained granule, and mixing.

The preparation method of the prescription 2 comprises the following steps:

(1) Cefprozil, sucrose, mannitol, sodium carboxymethylcellulose, colloidal silica, sodium chloride, aspartame are mixed into a premix.

(2) Adding purified water into the premix to prepare a soft material, adding a proper amount of purified water according to the wetting condition, averaging the dosage of single dose to 25-55 mu L, granulating by 14 meshes, drying and finishing by 12 meshes.

(3) Adding mixed fruit powder essence and strawberry powder essence into the obtained granule, and mixing.

The particles can be successfully prepared according to the method, and the sedimentation volume ratio of the particles in the prescription 1 and the particles in the prescription 2 is measured, and the result shows that the sedimentation volume ratio of the particles in the prescription 1 is 0.7 and does not meet the requirements (the standard is not lower than 0.9); in the formula 2, higher dosage of sodium carboxymethylcellulose is used as an internal auxiliary material, purified water is directly used for wetting to carry out granulation, the sedimentation volume ratio is 1.0, and the standard requirement is met.

Example 3

Cefprozil dry suspension was prepared according to the recipe in table 3.

TABLE 3 Table 3

The preparation method comprises the following steps:

The dissolution curve of the prescription sample is measured by taking purified water as dissolution medium, and compared with the original developing agent (Shi Guibao 5B03843 batch), the dissolution method adopts a slurry method (Chinese pharmacopoeia 2010 edition four general rule 0931 second method), the rotating speed is 50 revolutions per minute, the volume of the medium is 900ml, and 5ml of solution is respectively taken as sample solution after 5min, 10min, 15min, 20min and 30 min. The results are shown in Table 4 and FIGS. 1-8.

TABLE 4 Table 4

Wherein, the dissolution rates of the prescription 2, 3, 5 and 6 groups of 5min are faster than that of the original grinding, the dissolution rates of the prescription 1 and 4 are slow, the dissolution rates are lower, and the dissolution rates of the prescription 7 and 8 are slightly slow. It can be seen that the amount of sodium carboxymethylcellulose and sodium chloride used affects the dissolution effect.

Further, dissolution profiles of the formulation 5 and the raw preparation were compared in a pH1.0 hydrochloric acid solution, a pH4.0 acetate buffer solution, and a pH6.8 phosphate buffer solution, and dissolution (%) results are shown in Table 5.

TABLE 5

As can be seen from Table 5, the dissolution profile of the formulation 5 of the present invention was superior to that of the original formulation at pH1.0, and the dissolution profile was consistent with that of the original formulation from the overall characteristics of the dissolution profile, although the individual data of the dissolution profiles were 1-2% different at pH4.0 and 6.8.

The previous description of the disclosed embodiments is provided to enable any person skilled in the art to make or use the present invention. Various modifications to the embodiments described above will be readily apparent to those skilled in the art, and the generic principles defined herein may be applied to other embodiments without departing from the spirit or scope of the invention. Thus, the present invention is not intended to be limited to the embodiments shown herein but is to be accorded the widest scope consistent with the principles and novel features disclosed herein.

Claims

1. The cefprozil dry suspension is characterized by comprising the following raw materials in parts by weight:

125mg of cefprozil is added,

sucrose 555mg, which is added to the mixture,

280mg of mannitol and the total amount of the components,

6mg of sodium carboxymethylcellulose,

the colloidal silica was present in an amount of 5mg,

4mg of sodium chloride, which is added to the mixture,

aspartame 2.5mg,

1mg of mixed fruit powder essence,

1mg of strawberry powder essence;

(1) Mixing cefprozil, sucrose, mannitol, sodium carboxymethyl cellulose, colloidal silicon dioxide, sodium chloride and aspartame into a premix;

(2) Adding purified water into the premix to prepare a soft material, adding a proper amount of purified water according to the wetting condition, averaging to the dosage of 25-55 mu L of single dose, granulating by 14 meshes, drying, and finishing by 12 meshes;