CN104434869A - Cefdinir capsule and preparation method thereof - Google Patents

Abstract

The invention relates to a pharmaceutical preparation and preparation thereof and particularly relates to a cefdinir capsule and a preparation method thereof. The cefdinir capsule is prepared from a capsule shell and a content inside the capsule shell, wherein the content is particles containing cefdinir and the particles are prepared from the following raw and auxiliary materials in parts by weight: 100 parts of cefdinir, 30-60 parts of low-substituted hydroxypropyl cellulose LH-22, 4-8 parts of polyoxyethylene(40) stearate and 1-3 parts of magnesium stearate. The capsule is prepared from cefdinir raw medicinal materials, and the optimal proportion of the component is determined, so that the capsule s high in safety and convenient and safe to take. The hard capsule can effectively cover up objectionable odor of the medicine, and is easy to swallow and good in compliance.

Description

A kind of Cefdinir capsule agent and preparation method thereof

Technical field

The present invention relates to pharmaceutical preparation and preparation thereof, particularly a kind of Cefdinir capsule preparation and preparation method thereof.

Background technology

Cefdinir crude drug be micro-yellow to yellow crystalline powder, have micro-smelly.Slightly molten in 0.1mol/L phosphate buffer [0.1mol/L disodium phosphate soln-0.1mol/L potassium dihydrogen phosphate (2:1)], insoluble in water, ethanol or ether.Crude drug has unformed and crystal type two kinds, and document shows light and water unstable, and the stability of crystal type is greater than unformed; The dissolubility of crude drug is very poor, and will be therefore important reference index with dissolution in preparation research process, the granularity of crude drug also affects its dissolubility, but granularity too carefully affects fill.A large amount of Pharmacokinetic study results points out this medicine oral administration biaavailability good, and oral Absorbable rod is rapid, and transdermal is better, and extremely stable to beta-lactamase, dosage is also little, is applicable to very much being developed to oral dosage form capsule.

Cefdinir is the third generation semi-synthetic oral cephalosporin class antibiotic, this medicine is oral enter human body after produce antibacterial action by the synthesis of anti-bacteria cell wall, overcome Third generation Cephalosporins antibiotic and deficiency to Glan negative bacterium effect difference strong to the effect of Glan positive bacteria, all antibacterial activity is had to gram positive bacteria and negative bacterium, and most of beta-lactamase is stablized, a kind of broad ectrum antibiotic of extensive use clinically, be used for various common infection, seldom as first aid using medicine, therefore be developed to capsule adult should swallow, meet clinical practice.

For this kind of beta-lactam antibiotic of cefdinir, it does not have long-time stability under solution state, easily causes allergic reaction, and issuable microgranule in transfusion use procedure, add the risk to body tissue injury.Not only safety is high to make oral solid formulation, and taking convenience safety, and hard capsule effectively can cover the bad smell of medicine, is easy to swallow, and various color and lettering design make medicine have more identification, thus effectively improve the compliance of medication.

Summary of the invention

Technical problem to be solved by this invention is to provide a kind of Cefdinir capsule agent, also provides its preparation method in addition.

The technical scheme that the present invention solves the problems of the technologies described above is:

A kind of Cefdinir capsule agent, be made up of capsule shells and content thereof, described content is the granule containing cefdinir, and described granule is prepared from by the supplementary material of following weight portion:

Cefdinir 100 parts

Low-substituted hydroxypropyl cellulose LH-22 30 ~ 60 parts

S6 4 ~ 8 parts

Magnesium stearate 1 ~ 3 part.

Preferred described granule is prepared from by the supplementary material of following weight portion:

Cefdinir 100 parts

Low-substituted hydroxypropyl cellulose LH-22 40 parts

S6 6 parts

Magnesium stearate 2 parts.

The preparation method of above-mentioned capsule, step is as follows:

(1) cefdinir is got in 60 DEG C of cold drying;

(2) get s6 in 60 DEG C of meltings, molten condition machine progressively adds cefdinir mix homogeneously, and cooling, pulverized 150 orders for subsequent use;

(3) get low-substituted hydroxypropyl cellulose and magnesium stearate 55 ~ 65 DEG C of cold drying, mixing, cross No. 5 medicine inspections and sieve 100 orders, mix homogeneously with step (2) gained mixture, moisture to be checked and assay;

(4) detection level, moisture is sampled;

(5) after qualified, get No. 3 capsule shells, the gauge being 0.1g by cefdinir every content calculates every capsules should fill weight, fill capsule.

The preferred prescription of the present invention is through screening and obtains, and screening process is as follows:

one. supplementary product consumption screens

According to domestic adjuvant development and application situation, in conjunction with the prescription of reference preparation, low-substituted hydroxypropyl cellulose (L-HPC), polyoxyethylene stearate (40) ester (S-40), magnesium stearate is selected to be that adjuvant is tested, the kind of component each in prescription and consumption are screened, for ensureing product quality and the large production of enterprise, emphasis is using the mobility of supplementary material mixed-powder and dissolving out capability as main evaluation index.

Mobility is to weight differential, the uniformity of dosage units of capsule and operating influence is comparatively large normally, it is generally acknowledged angle of repose θgood fluidity when≤30 °, θthe demand of mobility in production process can be met when≤40 °; During degree of compression C<20%, the mobility of powder is better.

The mensuration of dissolution measures according to the carrying out specified under existing 2010 editions Chinese Pharmacopoeia Cefdinir capsule items completely, adopts the second method paddle method, and the stripping quantity limit of the every capsules of States Pharmacopoeia specifications 30min at least should be labelled amount 75%.

1. the screening (L-HPC) of low-substituted hydroxypropyl cellulose

Low-substituted hydroxypropyl cellulose is a kind of newtype drug adjuvant, and substitution value is different with model, plays a role also different.Wherein LH-20, LH-30 two profiles number for substitution value be 13%; LH-11, LH-21, LH-31 substitution value is 11%, is medium substitution value; LH-32 and LH-22 is lower substitution value, only has the hydroxypropyl substitution value of 8%, lot of documents shows that lower substitution value can improve disintegrating property better, LH-32 particle diameter only has 25 μm, the mean diameter of LH-22 is 40 μm, mobility is better than LH-32, therefore experimental selection model be the L-HPC of LH-22 as filling disintegrating agent, respectively research is compared thus screening to this kind of model of the L-HPC that three different manufacturers are produced.With reference to reference preparation content gross weight (about 0.15g), therefore design the consumption of following three levels.

Consumption screening (Mei Li consumption unit: mg) of the Japanese SHIN-ETSU HANTOTAI L-HPC of table 1

Consumption screening (Mei Li consumption unit: mg) of table 2 Anhui L-HPC

Consumption screening (Mei Li consumption unit: mg) of table 3 Hubei L-HPC

Table 4 each prescription primary evaluation index checking result

Evaluation of result:

Can be seen by data in table, the optimum amount of low-substituted hydroxypropyl cellulose is every 40mg, and the adjuvant performance of the same model that different manufacturer produces has different, the LH-22 type L-HPC of three different manufacturers, it seems that outward appearance be white powder, and particle diameter difference is little, all can cross 100 orders.

2. the screening (S-40) of polyoxyethylene stearate (40) ester

According to the conventional amount used of surfactant, following several different amounts is designed in experiment, the import S-40 adopted is that BASF Corp. of Germany produces, and domestic S-40 is that Nanjing WeiEr chemical engineering Co., Ltd produces, and screens respectively to import and the domestic research that compares.

Consumption screening (Mei Li consumption unit: mg) of the domestic S-40 of table 5

Consumption screening (Mei Li consumption unit: mg) of table 6 import S-40

Table 7 each prescription primary evaluation index checking result

Evaluation of result:

Can be seen by data in table, the optimum amount of polyoxyethylene stearate (40) ester is every 6mg, and the difference in mobility and dissolving out capability of Greasy Wool is little.Polyoxyethylene stearate (40) ester is waxy solid surfactant, consumption seldom just can meet formulation requirements, have and therefore need melting to disperse more than the characteristic of 60 ° of meltings, therefore when process choice process, selecting to make it better be scattered in particle surface by adding mixing in crude drug after its melting, after drying, pulverizing No. 9 sieves together with crude drug.

3. the screening of magnesium stearate

Magnesium stearate is conventional lubricant, can reduce the frictional force between powder, increases mobility.It is hydrophobicity, is attached to material surface, affects dissolution medium and enters inside, can slow down disintegrate stripping when consumption is excessive or incorporation time is long.Conventional amount used is 0.25-2%.Magnesium stearate is produced by Anhui Shanhe Medical Accessary Material Co., Ltd..

Consumption screening (Mei Li consumption unit: mg) of table 8 magnesium stearate

Table 9 each prescription primary evaluation index checking result

Prescription	The degree of compression (%)	Angle of repose (°)	30min accumulative dissolution (%)
				100728-1	25.13	31.96	91.34
100728-2	22.52	31.15	92.05
				100728-3	20.41	28.68	90.10

Evaluation of result:

The optimum amount of magnesium stearate is every 2mg, both meets mobile performance, also can not affect stripping, but strictly will control incorporation time.

4. the sample flow made of different grain size crude drug and dissolving out capability are investigated

Determining in prescription after supplementary product consumption, how investigate different its mobility of crude drug of another batch of granularity of same manufacturer production and dissolving out capability more further according to best prescription, Integrated comparative, determines final prescription.

Table 10 different grain size crude drug pilot sample indices is investigated

table 11 different grain size crude drug pilot sample stripping result

Different grain size crude drug pilot sample stripping curve figure is see Fig. 1.

The Cefdinir capsule accumulation stripping curve figure obtained according to the crude drug of 3 kinds of different-grain diameters, can obviously find out that particle diameter is less, stripping is better.But particle diameter is too small, be less than below 200 orders, occur that caking phenomenon hinders stripping, poor fluidity during fill in dissolution fluid, unsuitable capsule manufacture is used.80 ~ 100 object crude drug mobility are fine, but stripping is slow, and the to sum up comparison of different-grain diameter, selects 150 order cefdinir granularities, can meet mobility requirement, can be good at the stripping index request reaching insoluble drug.

The present invention has following beneficial effect:

Cefdinir crude drug is made capsule by the present invention, and determines the optimal proportion of each component, and safety is high, and taking convenience safety, and hard capsule effectively can cover the bad smell of medicine, and be easy to swallow, compliance is better.

Accompanying drawing explanation

Fig. 1 is different grain size crude drug pilot sample stripping curve figure.

Detailed description of the invention

Embodiment 1:(screens gained optimizing prescriptions)

Cefdinir 100 parts

Low-substituted hydroxypropyl cellulose (LH-22) 40 parts

Polyoxyethylene stearate (40) ester 6 parts

Magnesium stearate 2 parts

Technical process is as follows:

A. cefdinir is got in 60 DEG C of cold drying;

B. get polyoxyethylene stearate (40) ester in 60 DEG C of meltings, molten condition machine progressively adds cefdinir mix homogeneously, and cooling, pulverized 150 orders for subsequent use;

C. get low-substituted hydroxypropyl cellulose and magnesium stearate low temperature (60 DEG C) drying, mixing, cross No. 5 medicine inspections sieve (100 order), mix homogeneously with the mixture of principal agent under b item and polyoxyethylene stearate (40) ester, moisture to be checked and assay;

D. detection level, moisture is sampled;

E., after qualified, get No. 3 capsule shells, the gauge being 0.1g by cefdinir every content calculates every capsules should fill weight, fill capsule.

Embodiment 2:

Cefdinir 100 parts

Low-substituted hydroxypropyl cellulose (LH-22) 30 parts

Polyoxyethylene stearate (40) ester 4 parts

Magnesium stearate 3 parts

Technical process is as follows:

A. cefdinir is got in 60 DEG C of cold drying;

B. get polyoxyethylene stearate (40) ester in 60 DEG C of meltings, molten condition machine progressively adds cefdinir mix homogeneously, and cooling, pulverized 150 orders for subsequent use;

C. get low-substituted hydroxypropyl cellulose and magnesium stearate low temperature (60 DEG C) drying, mixing, cross No. 5 medicine inspections sieve (100 order), mix homogeneously with the mixture of principal agent under b item and polyoxyethylene stearate (40) ester, moisture to be checked and assay;

D. detection level, moisture is sampled;

E., after qualified, get No. 3 capsule shells, the gauge being 0.1g by cefdinir every content calculates every capsules should fill weight, fill capsule.

Claims (3)

1. a Cefdinir capsule agent, is made up of capsule shells and content thereof, it is characterized in that, described content is the granule containing cefdinir, and described granule is prepared from by the supplementary material of following weight portion:

Cefdinir 100 parts

Low-substituted hydroxypropyl cellulose LH-22 30 ~ 60 parts

S6 4 ~ 8 parts

Magnesium stearate 1 ~ 3 part.

2. capsule compositions according to claim 1, is characterized in that, wherein said granule is prepared from by the supplementary material of following preferred weight portion:

Cefdinir 100 parts

Low-substituted hydroxypropyl cellulose LH-22 40 parts

Polyoxyethylene stearate 40 ester 6 parts

Magnesium stearate 2 parts.

3. a preparation method for Cefdinir capsule agent described in claim 1, step is as follows:

(1) cefdinir is got in 60 DEG C of cold drying;

(2) get s6 in 60 DEG C of meltings, molten condition machine progressively adds cefdinir mix homogeneously, and cooling, pulverized 150 orders for subsequent use;

(3) get low-substituted hydroxypropyl cellulose and magnesium stearate 55 ~ 65 DEG C of cold drying, mixing, cross No. 5 medicine inspections and sieve 100 orders, mix homogeneously with step (2) gained mixture, moisture to be checked and assay;

(4) detection level, moisture is sampled;

(5) after qualified, get No. 3 capsule shells, the gauge being 0.1g by cefdinir every content calculates every capsules should fill weight, fill capsule.