A kind of cefuroxime axetil tablets and preparation method thereof
Technical field
The invention belongs to the pharmaceutical preparations technology field, in particular to cefuroxime axetil tablets of a kind of in vivo and in vitro Fast Stripping and preparation method thereof.
Background technology
CEFUROXIME AXETIL (cefuroxime axetil) is semisynthetic second generation cephalosporin, and has a broad antifungal spectrum all has stronger antibacterial activity to Gram-positive and negative bacterium.The active ingredient of cefuroxime axetil tablets is cefuroxime, it is oral in gastrointestinal absorption enters body, under the esterase effect, be hydrolyzed to rapidly cefuroxime, by combining with one or more penicillin-binding proteins (PBPs), the Cell wall synthesis of anti-bacteria somatoblast, thereby performance antibacterial action.CEFUROXIME AXETIL is close ester medicine, and is unstable in wet, thermal environment, and bitter in the mouth, and poorly water-soluble is difficult to absorb, and bioavailability is low, and dissolution rate is the limiting factor of drug absorption.
In order to improve the dissolution rate of cefuroxime axetil tablets, prior art has been reported a large amount of prescriptions and technical study test and technology.CN101874791A discloses a kind of raising cefuroxime axetil tablets, it is take CEFUROXIME AXETIL as the effective active composition, take microcrystalline Cellulose as filler, both share carboxymethyl starch sodium, crospolyvinylpyrrolidone and are disintegrating agent, calcium carbonate is stabilizing agent, magnesium stearate is lubricant, white carbon is fluidizer, sodium lauryl sulphate is cosolvent, polyvinylpyrrolidone is binding agent, the employing wet granulation is prepared, and wherein dissolution is more than 90% (15min), more than 95% (45min).Disintegrating agent and surface activity and more that this technology adopts, production cost is higher, easily occurs simultaneously the risk that crude drug variable color and related substance increase in the wet-granulation process.CN101606914A discloses a kind of cefuroxime axetil tablets that is applicable to direct pressed powder, this tablet mainly is by increasing the flowability of adjuvant, reach the direct powder compression effect of said preparation, but the bulk density of the adjuvant that requires is large, good fluidity, wherein the bulk density of disintegrating agent is greater than 0.35g/cm
3, the bulk density of filler is greater than 0.38g/cm
3, this requires too high to adjuvant, increased cost of supplementary product, and while this product need to could be disperseed complete in 10min, fails to reach tablet requirement in the pharmacopeia.CN101703448A discloses a kind of direct compression technique of cefuroxime axetil tablets, cross 40 mesh sieves by CEFUROXIME AXETIL, stearic acid, microcrystalline Cellulose, cross-linking sodium carboxymethyl cellulose, silicon dioxide and sodium lauryl sulphate, then mixed 30 minutes in tempering tank, mixed powder forms with high speed rotating tablet machine direct compression.The dissolution of the cefuroxime axetil dispersible tablets of this technique preparation was lower than 65% in the time of 15 minutes.
Current, the tablet manufacturing of China is still extensive with common granulating tabletting process, and the direct compression of full-powder method is used less.The direct compression of full-powder method is different from common granulating tabletting process, and its material that requires for tabletting all is pulverous fine powder, and material compressibility and mobile quality will determine the quality of final products.Because the flowability of most drug powder and the Technology requirement that compressibility all can not satisfy direct compression of full-powder, and the tablet machine of most of manufacturing enterprises does not have good powder device, dust arrester and the prepressing device of raising, be difficult to guarantee carrying out smoothly of direct compression of full-powder process, so the application of the suitability for industrialized production of direct compression of full-powder method is subject to many restrictions.Compare with common granulating tabletting process, the direct compression of full-powder method has obvious technical advantage and cost advantage.At first, the direct compression of full-powder method has avoided heating and moisture on the impact of tablet and technique.In actual production; often can run into the medicine of some unstable chemcial property; esters, amide-type medicine such as facile hydrolysis; the phenolic hydroxyl group class medicine of easy oxidation, vitamin C etc.; these medicines tend to occur hydrolysis in common wet granule compression tablet method; or it is destroyed to be heated in the particle drying process, or because complex process causes medicine to see photolysis etc.For these problems, the direct compression of full-powder method can solve.The direct compression of full-powder method need not to granulate, and need not drying, thereby can effectively protect the quality stability of medicine, avoids its various unstable factors that cause because of wet granulation, thereby guarantees the quality of product.Simultaneously, the production technology of direct compression of full-powder method is simple, shortens the production cycle, enhance productivity, and the energy-and time-economizing, thus can reduce the production cost of product.
In sum, by researching and developing the standby cefuroxime axetil tablets of direct compression of full-powder legal system that a kind of stripping is fast, stability is high, cost is low, this seems particularly necessary.
Summary of the invention
In view of the deficiencies in the prior art, the object of the invention is to provides cefuroxime axetil tablets that a kind of stripping is fast, stability is high, cost is low and preparation method thereof by prescription and the technique of the standby cefuroxime axetil tablets of direct compression of full-powder legal system are studied.
In order to realize purpose of the present invention, the inventor studies by lot of experiments, has finally obtained following technical scheme:
A kind of cefuroxime axetil tablets is formed by the medicine carrying piller that contains CEFUROXIME AXETIL and filler, mix lubricant direct compression; Described medicine carrying piller prepares as follows and gets: take by weighing CEFUROXIME AXETIL and disintegrating agent and be dissolved or dispersed in acetone, solution or the suspension that forms is sprayed to coating and the dry medicine carrying piller that gets on the lactose pellet in fluid bed.
Preferably, described cefuroxime axetil tablets, wherein the weight ratio of CEFUROXIME AXETIL, disintegrating agent and lactose pellet is 1:0.07-0.12:1-5.
Further preferably, described cefuroxime axetil tablets, wherein the weight ratio of CEFUROXIME AXETIL, disintegrating agent and lactose pellet is 1:0.08-0.10:1.5-2.
Described filler is selected from following one or more: mannitol, microcrystalline Cellulose, pregelatinized Starch.
Described disintegrating agent is selected from following one or more: polyvinylpolypyrrolidone, cross-linking sodium carboxymethyl cellulose, carboxymethyl starch sodium.
Described lubricant is selected from following one or more: magnesium stearate, micropowder silica gel, Pulvis Talci.
A kind of preparation method according to above-mentioned cefuroxime axetil tablets comprises following steps: CEFUROXIME AXETIL and disintegrating agent are dissolved or dispersed in acetone, solution or the suspension that forms is sprayed to coating and the dry medicine carrying piller that gets on the lactose pellet in fluid bed; Gained medicine carrying piller and filler, mix lubricant is even, and direct compression forms.
Preferably, the preparation method of described cefuroxime axetil tablets is D80<25 micron by the particle size in the described suspension of grinding control step (1) wherein.
Here said term " D80 " refers to that particle diameter in the described suspension accounts for 80% less than 25 microns granule.
Compared with prior art, the present invention is outer at lactose pellet with CEFUROXIME AXETIL raw material coating, and medicine is evenly distributed on the piller surface, has greatly improved the specific surface area of medicine, raw material can be discharged rapidly, thereby improve drug dissolution and bioavailability.Find by experimental study, the cefuroxime axetil tablets of the present invention's preparation is according to " method detects dissolution under Chinese pharmacopoeia version cefuroxime axetil tablets in 2010 item, drug dissolution was greater than 98% in 15 minutes, it is 40 ℃ ± 2 ℃ in temperature, humidity is to carry out accelerated test under 75% ± 5% the condition, place highly stablely after 6 months, significantly be better than prior art.In addition, cefuroxime axetil tablet preparation process of the present invention is fairly simple, easy to operate, and production cost is low, is fit to industrialized great production.
Description of drawings
Fig. 1 is the cumulative leaching rate curve chart of the cefuroxime axetil tablets of embodiment 1 preparation.
Fig. 2 is the cumulative leaching rate curve chart of the cefuroxime axetil tablets of embodiment 2 preparations.
Fig. 3 is the cumulative leaching rate curve chart of the cefuroxime axetil tablets of embodiment 3 preparations.
Fig. 4 is the cumulative leaching rate curve chart of the cefuroxime axetil tablets of comparative example's preparation.
The specific embodiment
Form is described in further detail foregoing of the present invention again by the following examples, but this should be interpreted as that the scope of the above-mentioned theme of the present invention only limits to following embodiment, all technology that realizes based on foregoing of the present invention all belong to scope of the present invention.
Embodiment 1
Preparation technology:
(1) CEFUROXIME AXETIL is dissolved in 1 liter of acetone, adds polyvinylpolypyrrolidone, stir, ball mill grinding, control suspension particle diameter D80<25 microns, coating gets the medicine carrying piller on the lactose pellet being sprayed in fluid bed with the suspension that forms.
(2) with step (1) gained medicine carrying piller and mannitol and magnesium stearate mix homogeneously, direct compression namely gets cefuroxime axetil tablets.The dissolution of cefuroxime axetil tablets is according to " method detects under Chinese pharmacopoeia version cefuroxime axetil tablets in 2010 item, calculate accumulation stripping percentage rate, take time t as abscissa, average accumulated stripping percentage rate is vertical coordinate mapping, the results are shown in Figure the 1(accelerated test before).The testing result demonstration, 15 minutes the dissolution of cefuroxime axetil tablets of this example preparation reaches 99.5%, and content is 99.8%, and dispersed homogeneous degree has all disperseed complete at 1 minute.Be 40 ℃ ± 2 ℃ in temperature, humidity is to carry out accelerated test under 75% ± 5% the condition, places 6 months, and 15 minutes dissolution is 98.3%, and content is 99.4%, and dispersed homogeneous degree all disperseed complete in 1 minute 30 seconds.
Embodiment 2
Preparation technology:
(1) CEFUROXIME AXETIL is dissolved in 1 liter of acetone, adds polyvinylpolypyrrolidone, stir, ball mill grinding, control suspension particle diameter D80<25 microns, coating gets the medicine carrying piller on the lactose pellet being sprayed in fluid bed with the suspension that forms.
(2) with step (1) gained medicine carrying piller and pregelatinized Starch and magnesium stearate mix homogeneously, direct compression namely gets cefuroxime axetil tablets.The dissolution of cefuroxime axetil tablets is according to " method detects under Chinese pharmacopoeia version cefuroxime axetil tablets in 2010 item, calculate accumulation stripping percentage rate, take time t as abscissa, average accumulated stripping percentage rate is vertical coordinate mapping, the results are shown in Figure the 2(accelerated test before).The testing result demonstration, 15 minutes the dissolution of cefuroxime axetil tablets of this example preparation reaches 98.6%, and content is 99.9%, and dispersed homogeneous degree has all disperseed complete at 1 minute.Be 40 ℃ ± 2 ℃ in temperature, humidity is to carry out accelerated test under 75% ± 5% the condition, places 6 months, and 15 minutes dissolution is 98.1%, and content is 99.2%, and dispersed homogeneous degree all disperseed complete in 1 minute 30 seconds.
Embodiment 3
Preparation technology:
(1) CEFUROXIME AXETIL is dissolved in 1 liter of acetone, adds cross-linking sodium carboxymethyl cellulose, stir, ball mill grinding, control suspension particle diameter D80<25 microns, coating gets the medicine carrying piller on the lactose pellet being sprayed in fluid bed with the suspension that forms.
(2) with step (1) gained medicine carrying piller and pregelatinized Starch, magnesium stearate mix homogeneously, direct compression namely gets cefuroxime axetil tablets.The dissolution of cefuroxime axetil tablets is according to " method detects under Chinese pharmacopoeia version cefuroxime axetil tablets in 2010 item, calculate accumulation stripping percentage rate, take time t as abscissa, average accumulated stripping percentage rate is vertical coordinate mapping, the results are shown in Figure the 3(accelerated test before).The testing result demonstration, 15 minutes the dissolution of cefuroxime axetil tablets of this example preparation reaches 99.4%, and content is 99.7%, and dispersed homogeneous degree has all disperseed complete at 1 minute.Be 40 ℃ ± 2 ℃ in temperature, humidity is to carry out accelerated test under 75% ± 5% the condition, places 6 months, and 15 minutes dissolution is 98.6%, and content is 99.5%, and dispersed homogeneous degree all disperseed complete in 1 minute 30 seconds.
The comparative example
Take the CEFUROXIME AXETIL specification as 125mg, the stock and adjunct of producing 1000 dispersible tablets consists of:
Preparation technology:
Take by weighing the stock and adjunct of above-mentioned recipe quantity, cross 40 mesh sieves, then in tempering tank, mixed 30 minutes, mixed powder high speed rotating tablet machine direct compression.The dissolution of cefuroxime axetil tablets is according to " method detects under Chinese pharmacopoeia version cefuroxime axetil tablets in 2010 item, calculate accumulation stripping percentage rate, take time t as abscissa, average accumulated stripping percentage rate is vertical coordinate mapping, the results are shown in Figure the 4(accelerated test before).The testing result demonstration, 15 minutes the dissolution of cefuroxime axetil tablets of this example preparation reaches 62.9%, and content is 99.6%, and dispersed homogeneous degree all can not disperse complete at 2 minutes.Be 40 ℃ ± 2 ℃ in temperature, humidity is to carry out accelerated test under 75% ± 5% the condition, places 6 months, and 15 minutes dissolution is 54.3%, and content is 99.2%.