Preparation method of famotidine calcium and magnesium micro-pill type chewable tablets and products thereofTechnical field
The invention belongs to pharmaceutical field, and in particular to the preparation method of famotidine calcium and magnesium micro-pill type chewable tablets, further relate toProduct obtained by this method.
Background technology
Peptic ulcer is the multiple disease of digestive system, although the incidence of disease presence in country variant, different regions is poorIt is different, but it is still worldwide, global common disease, and illness rate is up to 5%~10% in crowd.Just have in about every 10 people1 people suffered from peptic ulcer.The pathogenesis of peptic ulcer, in addition to hydrochloric acid in gastric juice and Hp, there is some other factor to stomachAnd Duodenal Mucosa barrier causes to damage.The medicine for being clinically mainly used in treating peptic ulcer at present has proton pump suppressionAgent, stomach lining film protective agent and H2Receptor antagonist.
Calcium carbonate and magnesium hydroxide can quickly neutralize hydrochloric acid in gastric juice, alleviate sour related symptoms, but it is shorter to hold time, only 1~2h,It need to repeatedly take medicine, therefore alkalosis, high calcium hypermagnesemia etc. easily occurs, therefore its application is restricted.Famotidine was the 3rd generationH2Receptor antagonist, have to H2The characteristics of receptor affinity is high, gastric acid secretion inhibiting effect is than Cimetidine, ranitidine pointIt is not strong 20 times, 715 times, be used clinically for preventing stress ulcer, treatment duodenal ulcer, gastric ulcer and upper digestive tract go outBlood, also there is the effect of certain to GERD.There are some researches show：Famotidine is to treat functional dyspepsia FD most at presentEffective medicine, it is effective typically after 1h although famotidine onset time is more long, maintain efficacy time up to 8~12h.The compound preparation that famotidine calcium and magnesium chewable tablets is made up of famotidine, calcium carbonate and magnesium hydroxide, famotidine areAcid-suppressing medicine, and calcium carbonate and magnesium hydroxide are to act on stronger antacids, 3 kinds of medicines share with gastric acid secretion inhibiting and it is quick inWith the double effectses of hydrochloric acid in gastric juice.
Famotidine is easily degraded during storage, and particularly run into some has acid or alkaline matter group in itselfInto compound in, such as the compound preparation that famotidine and calcium carbonate and magnesium hydroxide form.Famotidine and its major impurityStructure it is as shown in Figure 1.There is document report：Famotidine and magnesium hydroxide are incompatible medicine, after both directly contact, are addedThe speed degraded of famotidine, and interfere and add relevant material, therefore in compound preparation, both must isolate.At present, have many relevant reports on famotidine calcium and magnesium chewable tablets both at home and abroad.There is document report：First by famotidineInclusion compound is prepared into, secondly, Famotidine inclusion compound and part calcium carbonate are pelletized, again, remaining calcium carbonate and magnesium hydroxideGranulation, finally, tabletting after two kinds of particles is mixed.Also there is Patents report, after famotidine is made into small pieces, then by carbonic acidThe hybrid particles of calcium and magnesium hydroxide are wrapped in famotidine die surfaces and carry out tabletting.Separately there is patent report, first not replace methodFourth is individually pelletized, tabletting after then being mixed with the hybrid particles of calcium carbonate and magnesium hydroxide.In addition there is patent report：First willFamotidine mixes with partial supplementary material, and calcium carbonate mixes with magnesium hydroxide and partial supplementary material, then mixed auxiliary by two kindsMaterial is mixed.After famotidine is made into micropill herein, one layer of barrier gown is first wrapped up, then wraps one layer of elastic clothing, finally by methodTabletting is carried out after not mixed for fourth coating micro-pill with the hybrid particles of magnesium hydroxide and calcium carbonate.
Micro-pill type tablet belongs to one kind of multiple unit type tablet, compared with traditional tablet, have its it is unique the advantages of, oneIt is that micropill can increase medicine and intestines and stomach contact area, improves drug bioavailability, ensure that medicine has inside goodAbsorb reappearance and good tablets in vitro behavior reappearance；In addition, the preparation defect of Individual cells is unlikely to whole preparationThe performance of unit drug effect is produced and had a strong impact on.The advantages of pellet tablet is most prominent is that the segmentation that dosage can be realized according to medication difference is adjustedIt is whole, combined release or more flexible dosage regimen can be achieved.Therefore, pellet tablet will have wide potential applicability in clinical practice.ButThat micro-pill type tablet also has certain technical barrier in preparation process, for example, micropill particle diameter, clothing film material, micropill and filling it is auxiliaryThe factor such as the ratio of material and tabletting is to influence the key whether micropill is crushed in tableting processes.Micro-pill type tablet producing technologyMany problems limit the extensive exploitation application of such preparation to a certain extent, so being badly in need of a kind of system of micropill tabletPreparation Method, it is not crushed in tableting processes micropill.
The content of the invention
In view of this, an object of the present invention is the preparation method for providing famotidine calcium and magnesium micro-pill type chewable tablets,Its preparation method is simple, can ensure that famotidine is stable in composition；The second object of the present invention is to provide by above-mentioned sideFamotidine calcium and magnesium micro-pill type chewable tablets made from method.
For achieving the above object, the present invention provides following technical scheme：
1st, the preparation method of the preparation method of famotidine calcium and magnesium micro-pill type chewable tablets, comprises the following steps：
(1) famotidine that particle diameter is 40~60 mesh is made in the famotidine of recipe quantity and pharmaceutically acceptable auxiliary materialMicropill, then famotidine micropill is coated, obtains famotidine coating micro-pill；
(2) calcium carbonate and hydroxide is made with pharmaceutically acceptable auxiliary material in the calcium carbonate of recipe quantity and magnesium hydroxideMagnesium granules；
(3) by famotidine coating micro-pill obtained by step (1) and calcium carbonate and magnesium hydroxide particle and medicine obtained by step (2)Acceptable auxiliary materials and mixing, tabletting on, produce the preparation method of famotidine calcium and magnesium micro-pill type chewable tablets.
Preferably, the coating is to wrap up barrier gown layer or/and elastic membrane clothing layer on the famotidine micropill surface.
Preferably, the method for the coating is first to put famotidine micropill in seed-coating machine, preheating, then wraps up barrier gownLayer to famotidine micropill weight increase by 10%~40% stops coating, then wraps up elastic membrane clothing layer to famotidine micropill weightIncrease by 20%~70% stops coating, obtains famotidine coating micro-pill.
Preferably, barrier gown layer (HPMC containing hydroxypropyl methylcelluloseE15), or pharmaceutically upper conventional isolationClothing layer material, such as hydroxypropyl cellulose (HPCE), or the mixture of hydroxypropyl methylcellulose and hydroxypropyl cellulose；The elasticityFilm clothing layer (kollicoat IR) containing IR, or other the elastic clothing commonly used in pharmacyLayer material, such as：Polyvinyl alcohol, xanthans, the neutral copolymer of ethyl acrylate and methyl methacrylate(EUDRAGITNE30D)。
It is furthermore preferred that the barrier gown layer and elastic membrane clothing layer are also containing one in talcum powder, polyethylene glycol, ethanol, waterKind is a variety of.
It is furthermore preferred that barrier gown membrane material and the parts by weight of famotidine micropill are as follows：69.23 parts of famotidine micropill,HPMCE15Or 6.923~27.69 parts of hydroxypropylcellulose.
The parts by weight of elastic clothing layer material and famotidine micropill are as follows：96.92 parts of famotidine micropill and kollicoat15.50~54.26 parts of IR；Or 96.92 parts of famotidine micropill, 15.50~54.26 parts of EUDRAGITNE30D；Or method is not replaced0.5~5 part of 96.92 parts of fourth micropill, 15.50~54.26 parts of polyvinyl alcohol and xanthans.
Preferably, the pharmaceutically acceptable auxiliary material includes filler, wetting agent, antiplastering aid, adhesive, pigment or rectifiedOne or more in taste agent.
It is furthermore preferred that the wetting agent is water or ethanol solution；The filler is microcrystalline cellulose, starch, pregelatinatedOne or more in starch, lactose, mannitol, sucrose or xylitol；The antiplastering aid is talcum powder, silica, tristearinOne or more in sour magnesium or glycerin monostearate；Described adhesive be polyvinylpyrrolidone, hydroxypropyl methylcellulose andOne or more in hydroxypropyl cellulose；The pigment is red ferric oxide；The flavouring is mannitol, sucrose, SteviosideOr the one or more in menthol.
It is furthermore preferred that in step (1), the preparation method of the famotidine micropill is as follows：
A. female stage is played：The famotidine of recipe quantity is well mixed with filler, after preheating spray into adhesive to method notThe famotidine piller that particle diameter is 60~80 mesh is packed to for fourth, is sieved for subsequent use；
B. the micropill long megastage：Famotidine piller made from step a is sprayed into the adhesive containing filler, particle diameter is madeFor the micropill of 40~60 mesh, dry；
Or it is prepared as follows：Blank capsule core is placed in fluid bed, then by famotidine and filler, flavouringAfter being mixed with adhesive on sandblasting to Blank Pellets, the micropill that particle diameter is 40~60 mesh is made, dries.
In the above method, famotidine and each auxiliary material are as follows by weight：
(1) female stage is played
10 parts of famotidine, 5 parts~30 parts of sucrose, 10~40 parts of microcrystalline cellulose and HPMCE151~2 part；
Or 10 parts of famotidine, 5 parts~30 parts of starch, 10~40 parts of microcrystalline cellulose and HPMCE151~2 part；
(2) the micropill long megastage
41 parts of famotidine piller, 8 parts~16 parts of sucrose, 10~30 parts of microcrystalline cellulose, HPMCE151~4 part；
Or famotidine plays female 41 parts of piller, 8 parts~16 parts of lactose, 10~30 parts of microcrystalline cellulose, HPMCE151~4 part.
It is furthermore preferred that calcium carbonate and magnesium hydroxide are well mixed with flavouring and filler, wet granulation is subsequently placed inIn machine, and adding adhesive makes mixture form the particle that particle diameter is 20 mesh, is drying to obtain.
The each component of the calcium carbonate and magnesium hydroxide is as follows by weight：800 parts of calcium carbonate, magnesium hydroxide 165Part, 130~250 parts of sucrose, 280~520 parts of mannitol, HPMCE157~13 parts.
2nd, the famotidine calcium and magnesium micro-pill type nozzle as made from the preparation method of the famotidine calcium and magnesium micro-pill type chewable tabletsChew the preparation method of piece.
The beneficial effects of the present invention are：The invention discloses the preparation method of famotidine calcium and magnesium micro-pill type chewable tabletsPreparation method, by the way that famotidine to be prepared into the micropill of certain particle diameter, then with the coating that isolation is good and ductility is goodMaterial is coated to it, ensures that famotidine is isolated with magnesium hydroxide, and be not crushed in tableting processes；Again with calcium carbonate andMagnesium hydroxide particle mixes, finally by famotidine coating micro-pill and calcium carbonate and the particle of magnesium hydroxide and other are medicinal auxiliaryExpect mixed pressuring plate, obtained famotidine calcium and magnesium micro-pill type chews tablet stability and the uniformity is good, can preserve for a long time, effectivelyGround solves the problems, such as famotidine calcium and magnesium preparation stability difference and uniformity of dosage units difference.
Brief description of the drawings
In order that the purpose of the present invention, technical scheme and beneficial effect are clearer, the present invention provides drawings described below：
Fig. 1 is famotidine and main magazine structure chart (a. famotidines；B. impurity C (relative retention time 0.7)；c.Impurity D (relative retention time 1.2)).
Fig. 2 is the microscope figure of famotidine coating micro-pill.
Fig. 3 is the profile of famotidine calcium and magnesium micro-pill type chewable tablets.
Fig. 4 is the coating micro-pill after famotidine calcium and magnesium micro-pill type chewable tablets pulverizes.
Embodiment
Below in conjunction with accompanying drawing, the preferred embodiments of the present invention are described in detail.It is unreceipted specific in embodimentThe experimental method of condition, generally according to normal condition or according to the condition proposed by manufacturer.
In order to which the good famotidine calcium and magnesium micro-pill type chewable tablets of stability is made, famotidine and supplementary material are probed into firstCompatible implementations, by famotidine and the larger auxiliary material of dosage (such as microcrystalline cellulose, sucrose), by main ingredient：Auxiliary material=1：5 ratiosExample mixing；By famotidine and the less auxiliary material of dosage (such as talcum powder, magnesium stearate), by main ingredient：Auxiliary material=20：1 ratio is mixedClose；Then placed 10 days under the conditions of high temperature (60 DEG C), illumination (4500LX ± 500LX), high humidity (humidity 92.5%), respectivelyIn 0 day, the 10th day situation of change of the sampling detection about material, as a result as shown in table 1-2.
0 day table 1, famotidine and auxiliary material compatibility experiments result
| Numbering | Supplementary material title | Single miscellaneous % | Total miscellaneous % |
| 1 | Famotidine | 0.13 | 0.35 |
| 2 | Famotidine+calcium carbonate | 0.12 | 0.48 |
| 3 | Famotidine+magnesium hydroxide | 0.28 | 0.57 |
| 4 | Famotidine+HPMCE15 | 0.22 | 0.42 |
| 5 | Famotidine+kollicoat IR | 0.38 | 0.67 |
| 6 | Famotidine+mannitol | 0.11 | 0.45 |
| 7 | Famotidine+microcrystalline cellulose | 0.11 | 0.47 |
| 8 | Famotidine+pregelatinized starch | 0.12 | 0.36 |
| 9 | Famotidine+sucrose | 0.12 | 0.35 |
| 10 | Famotidine+iron oxide red | 0.35 | 0.64 |
| 11 | Famotidine+talcum powder | 0.11 | 0.47 |
| 12 | Famotidine+magnesium stearate | 0.11 | 0.37 |
| 13 | Famotidine+menthol | 0.11 | 0.45 |
| 14 | Famotidine+HPC | 0.25 | 0.43 |
| 15 | Famotidine+polyvinyl alcohol | 0.34 | 0.62 |
| 16 | Famotidine+xanthans | 0.12 | 0.47 |
| 17 | Famotidine+EUDRAGITNE30D | 0.13 | 0.48 |
| 18 | Famotidine+always mix auxiliary material | 0.39 | 1.52 |
10 days experimental results of compatibility of table 2, famotidine and auxiliary material
By the above results it can be seen that：After famotidine directly contacts with magnesium hydroxide, in bars such as high temperature, high humidity, illuminationUnder part, relevant material substantially rises；After famotidine directly contacts with elastic coatings material kollicoat IR, polyvinyl alcohol,Under hot conditions, relevant material substantially rises；After famotidine mixes with auxiliary materials such as iron oxide red, magnesium stearates, relevant materialAlso there is situation about substantially rising.Show famotidine and magnesium hydroxide, elastic coatings material kollicoat IR, iron oxideThere is obvious consistency problem in the supplementary materials such as red, magnesium stearate, be not suitable for directly contacting.
Famotidine calcium and magnesium micro-pill type chewable tablets is prepared according to previous experiments result, specific embodiment is as follows：
The preparation of embodiment 1, famotidine micropill
Method 1
The method for preparing famotidine micropill, comprises the following steps：
1st, female stage is played
(1) microcrystalline cellulose 200g, sucrose 100g, famotidine 100g and HPMC (HPMC are weighedE15)13.3g；
(2) HPMC is dissolved in water, the HPMC that mass fraction is 5% is madeE15Aqueous solution 267g；
(3) famotidine, sucrose and microcrystalline cellulose are well mixed, are placed in fluid bed side spray pot, use mass fractionFor 5% HPMCE15Aqueous solution whitewashing coating carries out making ball, and ball parameter is made in whitewashing：Coating solution liquid supply speed is 12-20r/min；Atomisation pressure is 0.16mpa；Temperature of charge is 35-40 DEG C；Rotary speed is 200-700r/min, and blower fan frequency is 18-20HZ；Treat that auxiliary material is packed to the piller of 60-80 mesh, stop coating, obtain famotidine piller, the famotidine piller gross weight of acquisitionFor 413.3g.
2nd, the micropill long megastage
(1) female stage famotidine piller 413.3g, sucrose 86.1g, microcrystalline cellulose 172.2g and hydroxypropyl first have been weighedBase cellulose (HPMCE15)20.7g；
(2) HPMC is dissolved in water, 3%HPMC is madeE15Aqueous solution 688.8g, then by microcrystalline cellulose,Sucrose is dissolved in 3%HPMCE15In the aqueous solution, suspension is prepared；
(3) famotidine piller made from is moved in fluid bed side spray pot, and method is carried out not with the whitewashing coating of above-mentioned suspensionFor fourth coating of pellets；Ball parameter is made in whitewashing：Coating solution liquid supply speed is 6-15r/min；Atomisation pressure is 0.2Mpa；Temperature of chargeFor 37-40 DEG C；Rotary speed is 500-800r/min；Blower fan frequency is 25HZ；Treat that particle diameter reaches 40-60 mesh, moisture is smallIn or equal to 3%, stop coating, obtain famotidine micropill, the gross weight of the famotidine micropill of acquisition is 692.3g.
Method 2
The method for preparing famotidine micropill, comprises the following steps：
1st, female stage is played
(1) microcrystalline cellulose 400g, starch 50g, famotidine 100g and HPMC (HPMC are weighedE15)15g；
(2) by HPMCE15Ethanol is dissolved in, the HPMC that mass fraction is 5% is madeE15Ethanol solution 300g；
(3) famotidine, starch and microcrystalline cellulose are well mixed, are placed in fluid bed side spray pot, use mass fractionFor 5% HPMCE15Ethanol solution whitewashing coating carries out making ball, treats that auxiliary material is packed to the piller of 60-80 mesh, stops coating, obtainFamotidine piller, the gross weight of the famotidine piller of acquisition is 565g.
2nd, the micropill long megastage
(1) female stage famotidine piller 565g, lactose 86.1g, microcrystalline cellulose 172.2g and hydroxypropyl have been weighedCellulose (HPMCE15)20.7g；
(2) by HPMCE15Water is dissolved in, the HPMC that mass fraction is 3% is madeE15Aqueous solution 688.8g, it is then that crystallite is fineDimension element, sucrose are dissolved in the HPMC that mass fraction is 3%E15In the aqueous solution, suspension is prepared；
(3) the famotidine piller 413.3g between 60-80 mesh is moved in fluid bed side spray pot, sprayed with above-mentioned suspensionSlurry coating carries out famotidine coating of pellets；Ball parameter is made in whitewashing：Coating solution liquid supply speed is 6-15r/min；Atomisation pressure is0.2mpa；Temperature of charge is 37-40 DEG C；Rotary speed is 500-800r/min；Blower fan frequency is 25HZ, treats that particle diameter reaches 40-60 mesh, and moisture is less than or equal to 3%, stops coating, obtains famotidine micropill.
In the present embodiment, famotidine micropill can also be prepared with the following method, be concretely comprised the following steps：Blank capsule core is putIn in fluid bed, then by mixed famotidine, sucrose, pregelatinized starch, microcrystalline cellulose and 5% polyvinylpyrrolidineKetone-K30 solution by powder add medicine to or dissolve in adhesive medicine-feeding be sprayed onto on Blank Pellets, be made particle diameter be 40-60 mesh micropill,Then dried 3 hours at 35~50 DEG C, it is standby.
Following methods can also be used to prepare, concretely comprised the following steps：By famotidine, sucrose, pregelatinized starch, microcrystalline celluloseSoftwood is made after element and the mixing of 5% polyvinylpyrrolidone-K30 solution, particle diameter then is made by extrusion spheronization machine in softwoodFor the micropill of 40-60 mesh, then dry 3 hours at 35~50 DEG C, it is standby.
Embodiment 2, famotidine coating of pellets
Method 1
The method of famotidine coating micro-pill coating, is comprised the following steps that：
1st, micropill bag barrier gown layer
(1) preparation of barrier gown coating solution
Weigh HPMC-E15 276.9g to be dissolved in suitable quantity of water, the HPMC that mass fraction is 3% is madeE15Aqueous solution 9230g,It is standby；
(2) micropill bag barrier gown
40-60 mesh famotidine micropills 692.3g is put to fluid bed bottom and sprayed in pot, with the HPMC that mass fraction is 3%E15The aqueous solution carries out bag barrier gown, and coating solution stops coating after being finished, and famotidine coating micro-pill gross weight is 969.2g after coating.
2nd, micropill bag elasticity clothing layer
(1) recipe quantity kollicoat IR 193.8g, talcum powder (Talc) 48.5g are weighed, both are well mixed, is claimed2786.5g water is taken, is added in said mixture, stirs into 8%kollicoat IR suspensions, crosses 80 mesh sieves, it is standby.
(2) the famotidine micropill 969.2g for being surrounded by barrier gown is weighed, is carried out with 8%kollicoat IR coating suspensionsCoating, stop coating after coating solution is finished, famotidine coating micro-pill is 1211.5g after coating.
Method 2
The method of famotidine coating of pellets, is comprised the following steps that：
1st, micropill bag barrier gown layer
(1) preparation of barrier gown coating solution
HPMC-E15 276.9g are weighed to be dissolved in suitable quantity of water, it is 3%HPMC-E15 aqueous solution 9230g that mass fraction, which is made,It is standby；
(2) micropill bag barrier gown
40-60 mesh famotidine micropills 692.3g is put to fluid bed bottom and sprayed in pot, is carried out with the 3%HPMC-E15 aqueous solutionBag barrier gown, coating solution stop coating after being finished.
2nd, micropill bag elasticity clothing layer
(1) Eudragit NE30D 234g, talcum powder 70g, dimethicone 0.17g, water 258g, by talcum powder are weighedIt is added to the water, is homogenized with refiner.This suspension is poured into Eudragit NE30D before use, is uniformly mixed, is produced；
(2) famotidine micropill 969.2g is weighed, is coated with 8%kollicoat IR coating suspensions, works as coating,Coating solution stops coating after being finished, and the gross weight of obtained famotidine coating micro-pill is 1109.2g.
The microscope figure of famotidine coating micro-pill is as shown in Figure 2.
The preparation of embodiment 3, calcium carbonate and magnesium hydroxide particle
The method for preparing calcium carbonate and magnesium hydroxide particle, is comprised the following steps that：
(1) calcium carbonate 8000g, magnesium hydroxide 1650g, mannitol 4000g, sucrose 300g, hydroxypropyl methyl cellulose are taken108.6g；
(2) HPMC is dissolved in suitable quantity of water, 3% HPMC aqueous solution 3620g is made；
(3) after being well mixed calcium carbonate, magnesium hydroxide, mannitol and sucrose, put in efficient wet granulator, Ran HoujiaEnter the granulation of the 3% hydroxypropyl methyl cellulose aqueous solution, calcium carbonate and magnesium hydroxide is formed the particle that particle diameter is 20 mesh, then in temperatureSpend to dry 0.5 hour under the conditions of 40-60 DEG C, obtain calcium carbonate and magnesium hydroxide particle, obtained calcium carbonate and magnesium hydroxideGrain gross weight is 14058.6g.
The preparation (10,000 dosages) of embodiment 4, famotidine calcium and magnesium micro-pill type chewable tablets
Method 1
The preparation method of famotidine calcium and magnesium micro-pill type chewable tablets, is comprised the following steps that：
(1) famotidine coating micro-pill 1211.5g, calcium carbonate and magnesium hydroxide particle 14058.6g, iron oxide red are weighed20g, menthol 30g and magnesium stearate 360g；
(2) by famotidine coating micro-pill, calcium carbonate and magnesium hydroxide particle, iron oxide red, menthol and magnesium stearateIt is well mixed with equal increments method, puts tabletting in tablet press machine, obtains famotidine calcium and magnesium micro-pill type chewable tablets, the famotidine of acquisitionCalcium and magnesium micro-pill type chewable tablets gross weight is 15680.1g.
Method 2
The preparation method of famotidine calcium and magnesium micro-pill type chewable tablets, is comprised the following steps that：
The profile of famotidine calcium and magnesium micro-pill type chewable tablets is made as shown in figure 3, from the figure 3, it may be seen that method is not replaced after tablettingFourth micropill shape is complete, shows the non-fragmentation of micropill structure in pressing process.Then by famotidine calcium and magnesium micro-pill type chewable tabletsPulverize, then observe famotidine micropill shape, structure is as shown in Figure 4.As shown in Figure 4, famotidine calcium produced by the present inventionMagnesium micro-pill type chewable tablets pulverizes rear micropill structural integrity, shows famotidine coating micro-pill Stability Analysis of Structures.
The method that experimental example 5, commonsense method prepare famotidine calcium and magnesium micro-pill type chewable tablets
Conventional method prepares famotidine calcium and magnesium micro-pill type chewable tablets, comprises the following steps：
(1) prescription
Famotidine 10g, calcium carbonate 800g, magnesium hydroxide 165g, pregelatinized starch 200g, microcrystalline cellulose 150g, hydroxylThird methylcellulose 6g, menthol 3g, red ferric oxide 2g, Stevioside 3g, magnesium stearate 20g.
(2) technique
Said components are made to 1000 in accordance with the following steps, are specially：
A. the hydroxypropyl methylcellulose of recipe quantity is configured to 5% ethanol solution it is standby；
B. the famotidine of recipe quantity, pregelatinized starch are well mixed, pelletized with hydroxypropyl methylcellulose solution, cross 20 meshWhole grain is sieved, in 40-60 DEG C of drying, obtains famotidine particle；
C. recipe quantity calcium carbonate, magnesium hydroxide, microcrystalline cellulose are well mixed, pelletized with hydroxypropyl methylcellulose solution,20 mesh sieve whole grains are crossed, in 40-60 DEG C of drying, obtain calcium carbonate, magnesium hydroxide particle；
D. by famotidine particle and calcium carbonate, magnesium hydroxide particle, menthol, red ferric oxide, Stevioside, magnesium stearateMixing 15 minutes, tabletting produce the famotidine calcium and magnesium chewable tablets of conventional method preparation.
Experimental example 6, the stability of famotidine calcium and magnesium micro-pill type chewable tablets and uniformity are investigated
Famotidine calcium and magnesium micro-pill type chewable tablets produced by the present invention is determined into its stability, and nozzle is made with commonsense methodChew piece to be contrasted, as a result as shown in table 1.
The stability of famotidine calcium and magnesium micro-pill type chewable tablets is made in table 1, the inventive method
Experiment shows above：Using famotidine coating of pellets technology prepare famotidine calcium and magnesium micro-pill type chewable tablets andChewable tablets prepared by conventional method compares, the stabilization of famotidine calcium and magnesium micro-pill type chewable tablets as made from the method for the present inventionProperty it is more preferable, without significant changes, main ingredient composition famotidine, calcium carbonate and magnesium hydroxide become relieving haperacidity ability without notable after six monthsChange, impurity content is also without showed increased.It is unqualified and the relevant material of chewable tablets prepared by conventional method is significantly raised.
Analyze reason：Famotidine unstable chemcial property in this product prescription, it is easy in preparation and storage processProduce catabolite.Famotidine is prepared after turning into coating of pellets, avoids famotidine first with there is connecing for compatibility materialTouch, secondly famotidine is formed to itself and protected, steam is to the relevant material of famotidine during avoiding keeping sample by moistureproof coatingInfluence.And in customary preparation methods, famotidine and magnesium hydroxide etc. have compatibility material directly to mix, therefore relevant material surpassesMark is many.
The uniformity of the obtained famotidine calcium and magnesium micro-pill type chewable tablets of the present invention is investigated, as a result as shown in table 2.
Famotidine calcium and magnesium micro-pill type chewable tablets uniformity of dosage units prepared by table 2, the inventive method
As a result show, the present invention obtained by famotidine calcium and magnesium micro-pill type chewable tablets uniformity of dosage units 90%-110% itBetween, A+1.80*S=8.60≤15 meet regulation.
Finally illustrate, preferred embodiment above is merely illustrative of the technical solution of the present invention and unrestricted, although logicalCross above preferred embodiment the present invention is described in detail, it is to be understood by those skilled in the art that can beVarious changes are made to it in form and in details, without departing from claims of the present invention limited range.