CN104906057A - Preparation method for famotidine calcium and magnesium pellet type chewable tablets and products - Google Patents
Preparation method for famotidine calcium and magnesium pellet type chewable tablets and products Download PDFInfo
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Abstract
The invention discloses a preparation method for famotidine calcium and magnesium pellet type chewable tablets and products. The preparation method includes the steps that a formulated amount of famotidine and medically acceptable excipient are made into famotidine pellets; the famotidine pellets are coated, and famotidine coating pellets are obtained; a formulated amount of calcium carbonate, a formulated amount of magnesium hydroxide and medically acceptable excipient are made into calcium carbonate and magnesium hydroxide particles; the famotidine coating pellets, the calcium carbonate and magnesium hydroxide particles and medically acceptable excipient are mixed evenly and pressed, and the famotidine calcium and magnesium pellet type chewable tablets are obtained. The made famotidine calcium and magnesium pellet type chewable tablets are good in stability and suitable for being stored for a long time. The preparation method well realizes compatibility of famotidine and magnesium hydroxide, well resolves the problem of pellet pressing breakage, and is simple in process, good in reproducibility and suitable for industrially producing famotidine calcium and magnesium pellet type chewable tablets.
Description
Technical field
The invention belongs to pharmaceutical field, be specifically related to the preparation method of famotidine calcium magnesium micro-pill type chewable tablet, also relate to product obtained by this method.
Background technology
Peptic ulcer is the multiple disease of digestive system, although there are differences at the sickness rate of country variant, different regions, it is still worldwide, global common disease, and in crowd, prevalence is up to 5% ~ 10%.1 people is just had to suffer from peptic ulcer in about every 10 people.The pathogenesis of peptic ulcer, except gastric acid and Hp, also has some other factor to cause damage to stomach and Duodenal Mucosa barrier.The medicine being mainly used in treating peptic ulcer at present clinically has proton pump inhibitor, gastric mucosa film protective agent and H
2receptor antagonist.
Calcium carbonate and magnesium hydroxide can fast in and gastric acid, alleviate sour related symptoms, but it is shorter to hold time, only 1 ~ 2h, need repeatedly take medicine, and therefore alkalosis, high calcium hypermagnesemia etc. easily occur, therefore its application is restricted.Famotidine is the 3rd generation H
2receptor antagonist, has H
2the feature that receptor affinity is high, gastric acid secretion inhibiting effect than cimetidine, ranitidine respectively strong 20 times, 715 times, clinically for preventing stress ulcer, treatment duodenal ulcer, gastric ulcer and upper gastrointestinal hemorrhage, also have certain curative effect to gastroesophageal reflux disease.There are some researches show: famotidine treats the most effective medicine of functional dyspepsia at present, although famotidine onset time is relatively more of a specified duration, generally effective after 1h, maintaining effective drug duration can reach 8 ~ 12h.The compound preparation that famotidine calcium magnesium chewable tablet is made up of famotidine, calcium carbonate and magnesium hydroxide, famotidine is acid suppression medicine, and calcium carbonate and magnesium hydroxide act on stronger antacid, 3 kinds of medicines share have gastric acid secretion inhibiting and fast in and the double effects of gastric acid.
Famotidine is easily degraded in storage process, particularly runs into some and itself has in the compound recipe of acidity or alkaline matter composition, the compound preparation that such as famotidine and calcium carbonate and magnesium hydroxide form.The structure of famotidine and major impurity thereof as shown in Figure 1.Have bibliographical information: famotidine and magnesium hydroxide are inconsistent medicine, after both directly contact, accelerate the degraded of famotidine, and interference adds related substance mutually, therefore in compound preparation, both must isolate.At present, many relevant reports about famotidine calcium magnesium chewable tablet are had both at home and abroad.Have bibliographical information: first famotidine is prepared into clathrate, secondly, Famotidine inclusion compound and part calcium carbonate are granulated, again, residue calcium carbonate and magnesium hydroxide are granulated, finally, by tabletting after two kinds of granule mixing.Also there is Patents to report, after famotidine is made small pieces, then the hybrid particles of calcium carbonate and magnesium hydroxide is wrapped in famotidine die surfaces carries out tabletting.Separately there is patent report, first famotidine is granulated separately, then carry out mixing rear tabletting with the hybrid particles of calcium carbonate and magnesium hydroxide.In addition have patent report: first mixed with partial supplementary material by famotidine, calcium carbonate mixes with magnesium hydroxide and partial supplementary material, is then mixed by two kinds of mixed adjuvants.After famotidine being made micropill herein, first wrap up one deck contagion gown, then bag one deck elasticity clothing, after finally being mixed by the hybrid particles of famotidine coated micropill and magnesium hydroxide and calcium carbonate, carry out tabletting.
Micro-pill type tablet belongs to the one of multiple unit type tablet, compared with traditional tablet, there is the advantage of its uniqueness, one is that micropill can increase medicine and gastrointestinal tract contact area, improve drug bioavailability, ensure that medicine has good body absorption repeatability and good tablets in vitro behavior repeatability; In addition, the preparation defect of Individual cells is unlikely to produce the performance of whole preparation unit drug effect to have a strong impact on.The most outstanding advantage of pellet tablet is the segmentation adjustment that can realize dosage according to medication difference, can realize combined release or dosage regimen more flexibly.Therefore, pellet tablet will have wide potential applicability in clinical practice.But micro-pill type tablet also has certain technical barrier in preparation process, the factors such as the ratio of such as micropill particle diameter, clothing membrane material, micropill and filling adjuvant and tabletting whether affect micropill in tableting processes by the key crushed.Many difficult problems of micro-pill type tablet producing technology limit the extensive exploitation application of this type of preparation to a certain extent, so be badly in need of a kind of preparation method of micropill tablet, are not crushed at tableting processes micropill.
Summary of the invention
In view of this, an object of the present invention is the preparation method providing famotidine calcium magnesium micro-pill type chewable tablet, and its preparation method is simple, can ensure that in compositions, famotidine is stablized; Two of object of the present invention is to provide the famotidine calcium magnesium micro-pill type obtained by said method chewable tablet.
For achieving the above object, the invention provides following technical scheme:
1, the preparation method of the preparation method of famotidine calcium magnesium micro-pill type chewable tablet, comprises the steps:
(1) famotidine of recipe quantity and pharmaceutically acceptable adjuvant being made particle diameter is 40 ~ 60 object famotidine micropills, then famotidine micropill is carried out coating, obtains famotidine coated micropill;
(2) calcium carbonate of recipe quantity and magnesium hydroxide and pharmaceutically acceptable adjuvant are made containing calcium carbonate and magnesium hydroxide particle;
(3) by step (1) gained famotidine coated micropill and step (2) gained calcium carbonate and magnesium hydroxide particle and pharmaceutically acceptable auxiliary materials and mixing, tabletting, obtains the preparation method of famotidine calcium magnesium micro-pill type chewable tablet.
Preferably, described coating is or/and elastica clothing layer at described famotidine micropill surface parcel contagion gown layer.
Preferably, the method of described coating is first put in seed-coating machine by famotidine micropill, preheating, then wrap up contagion gown layer to famotidine micropill weight and increase by 10% ~ 40% stopping coating, wrap up elastica clothing layer to famotidine micropill weight again and increase by 20% ~ 70% stopping coating, obtain famotidine coated micropill.
Preferably, described contagion gown layer is containing hypromellose (HPMC
e15), also can be pharmaceutically above conventional contagion gown layer material, as hydroxypropyl cellulose (HPC
e), or the mixture of hypromellose and hydroxypropyl cellulose; Described elastica clothing layer is containing IR (kollicoat IR), also can be other elasticity clothing layer materials conventional on pharmaceutics, as: the neutral copolymer (EUDRAGITNE30D) of polyvinyl alcohol, xanthan gum, ethyl acrylate and methyl methacrylate.
Preferred, described contagion gown layer and elastica clothing layer are also containing one or more in Pulvis Talci, Polyethylene Glycol, ethanol, water.
Preferred, the weight portion of contagion gown film material and famotidine micropill is as follows: famotidine micropill 69.23 parts, HPMC
e15or hyprolose 6.923 ~ 27.69 parts.
The weight portion of elasticity clothing layer material and famotidine micropill is as follows: famotidine micropill 96.92 parts and kollicoat IR 15.50 ~ 54.26 parts; Or famotidine micropill 96.92 parts, EUDRAGITNE30D 15.50 ~ 54.26 parts; Or famotidine micropill 96.92 parts, polyvinyl alcohol 15.50 ~ 54.26 parts and xanthan gum 0.5 ~ 5 part.
Preferably, described pharmaceutically acceptable adjuvant comprises one or more in filler, wetting agent, antiplastering aid, binding agent, pigment or correctives.
Preferred, described wetting agent is water or alcoholic solution; Described filler is one or more in microcrystalline Cellulose, starch, pregelatinized Starch, lactose, mannitol, sucrose or xylitol; Described antiplastering aid is one or more in Pulvis Talci, silicon dioxide, magnesium stearate or glyceryl monostearate; Described binding agent is one or more in polyvinylpyrrolidone, hypromellose and hydroxypropyl cellulose; Described pigment is red ferric oxide; Described correctives is one or more in mannitol, sucrose, stevioside or Mentholum.
Preferred, in step (1), the preparation method of described famotidine micropill is as follows:
A. play female stage: mixed homogeneously with filler by the famotidine of recipe quantity, spraying into binding agent to famotidine after preheating, to be packed to particle diameter be 60 ~ 80 object famotidine pillers, sieves for subsequent use;
B. micropill is grown up the stage: the famotidine piller obtained by step a sprays into the binding agent containing filler, and making particle diameter is 40 ~ 60 object micropills, dry;
Or prepare as follows: be placed in by celphere in fluid bed, after then being mixed with filler, correctives and binding agent by famotidine, sandblasting is on Blank Pellets, and making particle diameter is 40 ~ 60 object micropills, dry.
In said method, famotidine and each adjuvant as follows by weight:
(1) female stage is played
Famotidine 10 parts, sucrose 5 parts ~ 30 parts, microcrystalline Cellulose 10 ~ 40 parts and HPMC
e151 ~ 2 part;
Or famotidine 10 parts, starch 5 parts ~ 30 parts, microcrystalline Cellulose 10 ~ 40 parts and HPMC
e151 ~ 2 part;
(2) micropill is grown up the stage
Famotidine piller 41 parts, sucrose 8 parts ~ 16 parts, microcrystalline Cellulose 10 ~ 30 parts, HPMC
e151 ~ 4 part;
Or famotidine plays female piller 41 parts, lactose 8 parts ~ 16 parts, microcrystalline Cellulose 10 ~ 30 parts, HPMC
e151 ~ 4 part.
Preferred, calcium carbonate and magnesium hydroxide are mixed homogeneously with correctives and filler, are then placed in wet granulator, and add binding agent make mixture formed particle diameter be 20 object granules, be drying to obtain.
Described each component containing calcium carbonate and magnesium hydroxide is as follows by weight: calcium carbonate 800 parts, 165 parts, magnesium hydroxide, sucrose 130 ~ 250 parts, 280 ~ 520 parts, mannitol, HPMC
e157 ~ 13 parts.
The preparation method of the famotidine calcium magnesium micro-pill type chewable tablet 2, obtained by the preparation method of described famotidine calcium magnesium micro-pill type chewable tablet.
Beneficial effect of the present invention is: the preparation method that the invention discloses the preparation method of famotidine calcium magnesium micro-pill type chewable tablet, by famotidine being prepared into the micropill of certain particle diameter, then and coating material that ductility good good by isolation is to its coating, ensure that famotidine and magnesium hydroxide are isolated, and do not crushed in tableting processes; Mix with calcium carbonate and magnesium hydroxide particle again; finally by the granule of famotidine coated micropill and calcium carbonate and magnesium hydroxide and other pharmaceutic adjuvant mixed pressuring plates; obtained famotidine calcium magnesium micro-pill type chewable tablet stability and the uniformity all good; can preserve for a long time, efficiently solve the problem of famotidine calcium magnesium preparation poor stability and uniformity of dosage units difference.
Accompanying drawing explanation
In order to make object of the present invention, technical scheme and beneficial effect clearly, the invention provides following accompanying drawing:
Fig. 1 is famotidine and main magazine structure chart (a. famotidine; B. impurity C (relative retention time 0.7); C. impurity D (relative retention time 1.2)).
Fig. 2 is the microscope figure of famotidine coated micropill.
Fig. 3 is the profile of famotidine calcium magnesium micro-pill type chewable tablet.
Fig. 4 is the coated micropill after famotidine calcium magnesium micro-pill type chewable tablet pulverizes.
Detailed description of the invention
Below in conjunction with accompanying drawing, the preferred embodiments of the present invention are described in detail.The experimental technique of unreceipted actual conditions in embodiment, the usually conveniently conditioned disjunction condition of advising according to manufacturer.
In order to the famotidine calcium magnesium micro-pill type chewable tablet of obtained good stability, first the compatibility situation of famotidine and supplementary material is probed into, by the adjuvant (as microcrystalline Cellulose, sucrose etc.) of famotidine and large usage quantity, in principal agent: adjuvant=1:5 ratio mixing; By famotidine and the less adjuvant (as Pulvis Talci, magnesium stearate) of consumption, in principal agent: adjuvant=20:1 ratio mixing; Then place 10 days under high temperature (60 DEG C), illumination (4500LX ± 500LX), high humidity (humidity is 92.5%) condition, detect the situation of change of related substance respectively at sampling in 0 day, the 10th day, result is as shown in table 1-2.
Table 1, famotidine and adjuvant 0 day compatibility experiments result
| Numbering | Supplementary material title | Single assorted % | Total assorted % |
| 1 | Famotidine | 0.13 | 0.35 |
| 2 | Famotidine+calcium carbonate | 0.12 | 0.48 |
| 3 | Famotidine+magnesium hydroxide | 0.28 | 0.57 |
| 4 | Famotidine+HPMC E15 | 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+Pulvis Talci | 0.11 | 0.47 |
| 12 | Famotidine+magnesium stearate | 0.11 | 0.37 |
| 13 | Famotidine+Mentholum | 0.11 | 0.45 |
| 14 | Famotidine+HPC | 0.25 | 0.43 |
| 15 | Famotidine+polyvinyl alcohol | 0.34 | 0.62 |
| 16 | Famotidine+xanthan gum | 0.12 | 0.47 |
| 17 | Famotidine+EUDRAGITNE30D | 0.13 | 0.48 |
| 18 | Famotidine+always mixed adjuvant | 0.39 | 1.52 |
The compatibility 10 days experimental results of table 2, famotidine and adjuvant
As can be seen from the above results: after famotidine directly contacts with magnesium hydroxide, under the conditions such as high temperature, high humidity, illumination, related substance obviously rises; After famotidine directly contacts with elastic coatings material kollicoat IR, polyvinyl alcohol, under hot conditions, related substance obviously rises; After famotidine mixes with the adjuvant such as iron oxide red, magnesium stearate, also there is situation about obviously rising in related substance.Show that the supplementary material such as famotidine and magnesium hydroxide, elastic coatings material kollicoat IR, iron oxide red, magnesium stearate exists obvious consistency problem, be not suitable for direct contact.
Prepare famotidine calcium magnesium micro-pill type chewable tablet according to previous experiments result, specific embodiment is as follows:
The preparation of embodiment 1, famotidine micropill
Method 1
Prepare the method for famotidine micropill, comprise the steps:
1, female stage is played
(1) microcrystalline Cellulose 200g, sucrose 100g, famotidine 100g and hydroxypropyl methylcellulose (HPMC is taken
e15) 13.3g;
(2) hydroxypropyl methylcellulose is water-soluble, make the HPMC that mass fraction is 5%
e15aqueous solution 267g;
(3) by famotidine, sucrose and microcrystalline Cellulose mix homogeneously, being placed in fluid bed side spray pot, is the HPMC of 5% with mass fraction
e15aqueous 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 adjuvant is packed to 60-80 object piller, stop coating, obtain famotidine piller, the famotidine piller gross weight of acquisition is 413.3g.
2, micropill is grown up the stage
(1) female stage famotidine piller 413.3g, sucrose 86.1g, microcrystalline Cellulose 172.2g and hydroxypropyl methylcellulose (HPMC has been taken
e15) 20.7g;
(2) hydroxypropyl methylcellulose is water-soluble, make 3%HPMC
e15aqueous solution 688.8g, then by microcrystalline Cellulose, sucrose dissolved at 3%HPMC
e15in aqueous solution, prepare suspension;
(3) obtained famotidine piller moves in fluid bed side spray pot, carries out famotidine coating of pellets with above-mentioned suspension whitewashing coating; Ball parameter is made in whitewashing: coating solution liquid supply speed is 6-15r/min; Atomisation pressure is 0.2Mpa; Temperature of charge is 37-40 DEG C; Rotary speed is 500-800r/min; Blower fan frequency is 25HZ; Treat that particle diameter reaches 40-60 order, moisture is less than or equal to 3%, and stop coating, obtain famotidine micropill, the gross weight of the famotidine micropill of acquisition is 692.3g.
Method 2
Prepare the method for famotidine micropill, comprise the steps:
1, female stage is played
(1) microcrystalline Cellulose 400g, starch 50g, famotidine 100g and hydroxypropyl methylcellulose (HPMC is taken
e15) 15g;
(2) by HPMC
e15be dissolved in ethanol, make the HPMC that mass fraction is 5%
e15alcoholic solution 300g;
(3) by famotidine, starch and microcrystalline Cellulose mix homogeneously, being placed in fluid bed side spray pot, is the HPMC of 5% with mass fraction
e15alcoholic solution whitewashing coating carries out making ball, and treat that adjuvant is packed to 60-80 object piller, stop coating, obtain famotidine piller, the gross weight of the famotidine piller of acquisition is 565g.
2, micropill is grown up the stage
(1) female stage famotidine piller 565g, lactose 86.1g, microcrystalline Cellulose 172.2g and hydroxypropyl methylcellulose (HPMC has been taken
e15) 20.7g;
(2) by HPMC
e15water-soluble, make the HPMC that mass fraction is 3%
e15then microcrystalline Cellulose, sucrose dissolved are the HPMC of 3% at mass fraction by aqueous solution 688.8g
e15in aqueous solution, prepare suspension;
(3) the famotidine piller 413.3g between 60-80 order is moved in fluid bed side spray pot, carry out famotidine coating of pellets with above-mentioned suspension whitewashing coating; Ball parameter is made in whitewashing: coating solution liquid supply speed is 6-15r/min; Atomisation pressure is 0.2mpa; Temperature of charge is 37-40 DEG C; Rotary speed is 500-800r/min; Blower fan frequency is 25HZ, treat that particle diameter reaches 40-60 order, and moisture is less than or equal to 3%, stops coating, obtains famotidine micropill.
In the present embodiment, famotidine micropill can also be adopted and prepare with the following method, concrete steps are: be placed in by celphere in fluid bed, then mixed famotidine, sucrose, pregelatinized Starch, microcrystalline Cellulose and 5% polyvinylpyrrolidone-K30 solution being added medicine to by powder or dissolving in binding agent medicine-feeding is sprayed onto on Blank Pellets, making particle diameter is 40-60 object micropill, then 35 ~ 50 DEG C of dryings 3 hours, for subsequent use.
Also following method can be adopted to prepare, concrete steps are: make soft material by after famotidine, sucrose, pregelatinized Starch, microcrystalline Cellulose and the mixing of 5% polyvinylpyrrolidone-K30 solution, then soft material being made particle diameter by extrusion spheronization machine is 40-60 object micropill, again 35 ~ 50 DEG C of dryings 3 hours, for subsequent use.
Embodiment 2, famotidine coating of pellets
Method 1
The method of famotidine coated micropill coating, concrete steps are as follows:
1, micropill bag contagion gown layer
(1) preparation of contagion gown coating solution
Taking HPMC-E15 276.9g is dissolved in suitable quantity of water, makes the HPMC that mass fraction is 3%
e15aqueous solution 9230g, for subsequent use;
(2) micropill bag contagion gown
Being put by 40-60 order famotidine micropill 692.3g and spray in pot at the bottom of fluid bed, is the HPMC of 3% with mass fraction
e15aqueous solution carries out bag contagion gown, and coating solution is finished rear stopping coating, and after coating, famotidine coated micropill gross weight is 969.2g.
2, micropill bag elasticity clothing layer
(1) take recipe quantity kollicoat IR 193.8g, Pulvis Talci (Talc) 48.5g, by both mix homogeneously, take 2786.5g water, join in said mixture, stir into 8%kollicoat IR suspension, cross 80 mesh sieves, for subsequent use.
(2) take the famotidine micropill 969.2g being surrounded by contagion gown, carry out coating with 8%kollicoat IR coating suspensions, stopping coating after coating solution is finished, after coating, famotidine coated micropill is 1211.5g.
Method 2
The method of famotidine coating of pellets, concrete steps are as follows:
1, micropill bag contagion gown layer
(1) preparation of contagion gown coating solution
Taking HPMC-E15 276.9g is dissolved in suitable quantity of water, and making mass fraction is 3%HPMC-E15 aqueous solution 9230g, for subsequent use;
(2) micropill bag contagion gown
Put by 40-60 order famotidine micropill 692.3g and spray in pot at the bottom of fluid bed, carry out bag contagion gown with 3%HPMC-E15 aqueous solution, coating solution is finished rear stopping coating.
2, micropill bag elasticity clothing layer
(1) take Eudragit NE30D 234g, Pulvis Talci 70g, dimethicone 0.17g, water 258g, is added to the water Pulvis Talci, uses refiner homogenize.Pour this suspension into Eudragit NE30D before use, be uniformly mixed, to obtain final product;
(2) take famotidine micropill 969.2g, carry out coating, work as coating with 8%kollicoat IR coating suspensions, coating solution is finished rear stopping coating, and the gross weight of obtained famotidine coated micropill is 1109.2g.
The microscope figure of famotidine coated micropill as shown in Figure 2.
The preparation of embodiment 3, calcium carbonate and magnesium hydroxide particle
Prepare the method for calcium carbonate and magnesium hydroxide particle, concrete steps are as follows:
(1) calcium carbonate 8000g is got, magnesium hydroxide 1650g, mannitol 4000g, sucrose 300g, hydroxypropyl emthylcellulose 108.6g;
(2) hydroxypropyl methylcellulose is dissolved in suitable quantity of water, makes 3% hydroxypropyl methylcellulose aqueous solution 3620g;
(3) by after calcium carbonate, magnesium hydroxide, mannitol and sucrose mix homogeneously; set high in effect wet granulator; then add 3% hydroxypropyl emthylcellulose aqueous solution to granulate; making calcium carbonate and magnesium hydroxide form particle diameter is 20 object granules; under temperature is 40-60 DEG C of condition dry 0.5 hour again; obtain calcium carbonate and magnesium hydroxide particle, obtained calcium carbonate and magnesium hydroxide particle gross weight are 14058.6g.
The preparation (10,000 consumptions) of embodiment 4, famotidine calcium magnesium micro-pill type chewable tablet
Method 1
The preparation method of famotidine calcium magnesium micro-pill type chewable tablet, concrete steps are as follows:
(1) famotidine coated micropill 1211.5g is taken, calcium carbonate and magnesium hydroxide particle 14058.6g, iron oxide red 20g, Mentholum 30g and magnesium stearate 360g;
(2) by famotidine coated micropill, calcium carbonate and magnesium hydroxide particle, iron oxide red, Mentholum and magnesium stearate equal increments method mix homogeneously, put tabletting in tablet machine, obtain famotidine calcium magnesium micro-pill type chewable tablet, the famotidine calcium magnesium micro-pill type chewable tablet gross weight of acquisition is 15680.1g.
Method 2
The preparation method of famotidine calcium magnesium micro-pill type chewable tablet, concrete steps are as follows:
As shown in Figure 3, as shown in Figure 3, after tabletting, famotidine micropill shape is complete, shows that micropill structure is not cracked in pressing process for the profile of obtained famotidine calcium magnesium micro-pill type chewable tablet.Then pulverized by famotidine calcium magnesium micro-pill type chewable tablet, then observe famotidine micropill shape, structure as shown in Figure 4.As shown in Figure 4, the famotidine calcium magnesium micro-pill type chewable tablet that the present invention obtains pulverizes rear micropill structural integrity, shows famotidine coated micropill Stability Analysis of Structures.
Experimental example 5, commonsense method prepare the method for famotidine calcium magnesium micro-pill type chewable tablet
Conventional method prepares famotidine calcium magnesium micro-pill type chewable tablet, comprises the steps:
(1) prescription
Famotidine 10g, calcium carbonate 800g, magnesium hydroxide 165g, pregelatinized Starch 200g, microcrystalline Cellulose 150g, hypromellose 6g, Mentholum 3g, red ferric oxide 2g, stevioside 3g, magnesium stearate 20g.
(2) technique
Said components is made 1000 in accordance with the following steps, is specially:
A. the hypromellose of recipe quantity is mixed with 5% alcoholic solution for subsequent use;
B. by the famotidine of recipe quantity, pregelatinized Starch mix homogeneously, granulate with hypromellose cellulose solution, cross 20 mesh sieve granulate, in 40-60 DEG C of drying, obtain famotidine granule;
C. by recipe quantity calcium carbonate, magnesium hydroxide, microcrystalline Cellulose mix homogeneously, granulate with hypromellose cellulose solution, cross 20 mesh sieve granulate, in 40-60 DEG C of drying, obtain calcium carbonate, magnesium hydroxide particle;
D. by famotidine granule and calcium carbonate, magnesium hydroxide particle, Mentholum, red ferric oxide, stevioside, magnesium stearate mixes 15 minutes, and namely tabletting obtains famotidine calcium magnesium chewable tablet prepared by traditional method.
The stability of experimental example 6, famotidine calcium magnesium micro-pill type chewable tablet and uniformity are investigated
Famotidine calcium magnesium micro-pill type chewable tablet the present invention obtained measures its stability, and obtains chewable tablet with commonsense method and contrast, and result is as shown in table 1.
Table 1, the inventive method obtain the stability of famotidine calcium magnesium micro-pill type chewable tablet
More than experiment shows: the famotidine calcium magnesium micro-pill type chewable tablet adopting famotidine coating of pellets technology to prepare is compared with chewable tablet prepared by conventional method, the stability of the famotidine calcium magnesium micro-pill type chewable tablet obtained by method of the present invention is better, antacid ability is after six months without significant change, principal agent composition famotidine, calcium carbonate and magnesium hydroxide are without significant change, and impurity content is also without showed increased.And chewable tablet related substance prepared by conventional method obviously raises, defective.
Analyze reason: the famotidine unstable chemcial property in this product prescription, the easy generation catabolite in preparation and storage process.After famotidine preparation becomes coating of pellets, first avoid famotidine and have the contact of compatibility material, secondly famotidine is by moistureproof coating, forms protection to self, and the period steam of avoiding keeping sample is on the impact of famotidine related substance.And in customary preparation methods, famotidine and magnesium hydroxide etc. have compatibility material directly to mix, therefore related substance exceeds standard many.
Investigate the uniformity that the present invention obtains famotidine calcium magnesium micro-pill type chewable tablet, result is as shown in table 2.
Famotidine calcium magnesium micro-pill type chewable tablet uniformity of dosage units prepared by table 2, the inventive method
Result shows, and obtained by the present invention, famotidine calcium magnesium micro-pill type chewable tablet uniformity of dosage units is between 90%-110%, and A+1.80*S=8.60≤15 conform with the regulations.
What finally illustrate is, above preferred embodiment is only in order to illustrate technical scheme of the present invention and unrestricted, although by above preferred embodiment to invention has been detailed description, but those skilled in the art are to be understood that, various change can be made to it in the form and details, and not depart from claims of the present invention limited range.
Claims (10)
1. the preparation method of famotidine calcium magnesium micro-pill type chewable tablet, is characterized in that, comprise the steps:
(1) famotidine of recipe quantity and pharmaceutically acceptable adjuvant are made famotidine micropill, then famotidine micropill is carried out coating, obtain famotidine coated micropill;
(2) calcium carbonate of recipe quantity and magnesium hydroxide and pharmaceutically acceptable adjuvant are made containing calcium carbonate and magnesium hydroxide particle;
(3) by step (1) gained famotidine coated micropill and step (2) gained calcium carbonate and magnesium hydroxide particle and pharmaceutically acceptable auxiliary materials and mixing, tabletting, obtains famotidine calcium magnesium micro-pill type chewable tablet.
2. the preparation method of famotidine calcium magnesium micro-pill type chewable tablet according to claim 1, is characterized in that: described coating first wraps up contagion gown layer on described famotidine micropill surface, and then wrap up elastica clothing layer.
3. the preparation method of famotidine calcium magnesium micro-pill type chewable tablet according to claim 2, it is characterized in that: the method for described coating is first put in seed-coating machine by famotidine micropill, preheating, then wrap up contagion gown layer to famotidine micropill weight and increase by 10% ~ 40% stopping coating, wrap up elastica clothing layer to famotidine micropill weight again and increase by 20% ~ 70% stopping coating, obtain famotidine coated micropill.
4. the preparation method of famotidine calcium magnesium micro-pill type chewable tablet according to Claims 2 or 3, is characterized in that: described contagion gown layer is containing one or both in hypromellose and hydroxypropyl cellulose; Described elastica clothing layer is containing one or more in the neutral copolymer of polyvinyl alcohol, xanthan gum, ethyl acrylate and methyl methacrylate and IR.
5. the preparation method of famotidine calcium magnesium micro-pill type chewable tablet according to claim 4, is characterized in that: described contagion gown layer and elastica clothing layer are also containing one or more in Pulvis Talci, Polyethylene Glycol, ethanol, water.
6. the preparation method of famotidine calcium magnesium micro-pill type chewable tablet according to claim 1, is characterized in that: described pharmaceutically acceptable adjuvant comprise in filler, wetting agent, antiplastering aid, binding agent, pigment or correctives one or more.
7. the preparation method of famotidine calcium magnesium micro-pill type chewable tablet according to claim 6, is characterized in that: described wetting agent is water or alcoholic solution; Described filler is one or more in microcrystalline Cellulose, starch, pregelatinized Starch, lactose, mannitol, sucrose or xylitol; Described antiplastering aid is one or more in Pulvis Talci, silicon dioxide, magnesium stearate or glyceryl monostearate; Described binding agent is one or more in polyvinylpyrrolidone, hypromellose and hydroxypropyl cellulose; Described pigment is red ferric oxide; Described correctives is one or more in mannitol, sucrose, stevioside or Mentholum.
8. the preparation method of famotidine calcium magnesium micro-pill type chewable tablet according to claim 6 or 7, it is characterized in that: in step (1), the preparation method of described famotidine micropill is as follows:
A. play female stage: mixed homogeneously with filler by the famotidine of recipe quantity, spraying into binding agent to famotidine after preheating, to be packed to particle diameter be 60 ~ 80 object famotidine pillers, sieves for subsequent use;
B. micropill is grown up the stage: the famotidine piller obtained by step a sprays into the binding agent containing filler, and making particle diameter is 40 ~ 60 object micropills, dry;
Or prepare as follows: be placed in by celphere in fluid bed, after then being mixed with filler, correctives and binding agent by famotidine, sandblasting is on Blank Pellets, and making particle diameter is 40 ~ 60 object micropills, dry.
9. the preparation method of famotidine calcium magnesium micro-pill type chewable tablet according to claim 1; it is characterized in that: calcium carbonate and magnesium hydroxide are mixed homogeneously with correctives and filler; then be placed in wet granulator; and add binding agent make mixture formed particle diameter be 20 object granules, be drying to obtain.
10. the preparation method of the famotidine calcium magnesium micro-pill type chewable tablet obtained by the preparation method of famotidine calcium magnesium micro-pill type chewable tablet described in any one of claim 1 ~ 9.
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Cited By (3)
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| CN113143875A (en) * | 2020-12-30 | 2021-07-23 | 河南合智医药科技有限公司 | Taste-masking compound famotidine chewable tablet and preparation method thereof |
| CN113143876A (en) * | 2020-12-30 | 2021-07-23 | 河南合智医药科技有限公司 | Stable compound famotidine chewable tablet and preparation method thereof |
| CN114340599A (en) * | 2019-09-27 | 2022-04-12 | 强生消费者公司 | Gel chewable dosage form |
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| WO2022200897A1 (en) * | 2021-03-24 | 2022-09-29 | Johnson & Johnson Consumer Inc. | A pharmaceutical composition comprising famotidine |
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| CN104906057B (en) | 2018-03-02 |
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