CN104173370A - Calcium-containing effervescent tablet and preparation method and application - Google Patents
Calcium-containing effervescent tablet and preparation method and application Download PDFInfo
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Abstract
The invention discloses a calcium-containing effervescent tablet and its preparation method and application. The preparation method of the calcium-containing effervescent preparation comprises the following step: acid particles, alkali particles and a lubricant are mixed to obtain a calcium-containing effervescent preparation. The alkali particles are obtained by the following method: (i) calcium carbonate and vitamin D which have equal proportion are mixed to obtain a mixture 1; (ii) the mixture 1 is mixed with a pharmaceutically acceptable carrier to obtain a mixture 2; and (iii) the mixture 2 is mixed with a solution containing Opadry amb, and pelletization packaging is carried out so as to obtain the alkali particles. The acid particles are obtained by the following method: citric acid is mixed with an ethanol solution containing Opadry amb, and wet granulation is carried out so as to obtain the acid particles.
Description
Technical field
The present invention relates to calcium preparation, relate in particular to a kind of containing calcium effervescence tablet and its production and use.
Background technology
The current goods of replenishing the calcium, comprise instant effervescent particles, effervescent tablet etc., due to the reason of technique, in the time preserving, pay particular attention to, just be easy to rotten and oxidation once touch air, and technique itself is also very high to the requirement of environment, for example to control space humidity 40% with inferior.Still do not produce at present a kind of effective ways of effervescent tablet of preservation stable in the air.
In addition, the content due to vitamin D in the current goods of replenishing the calcium is very low, and it is very poor in the uniformity of replenishing the calcium in goods.
Therefore this area is in the urgent need to providing a kind of vitamin D content even, and the calcium-supplementing effervescence preparation of easily preserving, and a kind of low technique of environmental requirement that can prepare such preparation need to be provided.
Summary of the invention
The present invention aims to provide a kind of new calcic effervescent formulation and preparation method thereof.
In a first aspect of the present invention, a kind of preparation method of calcic effervescent formulation is provided, described method comprises step: granulates, alkali granule and mix lubricant are obtained to calcic effervescent formulation;
Described alkali granule obtains by following method:
(i) calcium carbonate and vitamin D are mixed and (use the calcium carbonate of vitamin D homogenous quantities to mix with it according to point mode equal proportions such as quality, obtain elementary mixture, then use with the calcium carbonate of the quality such as elementary mixture and be mixed to get secondary mixture, by that analogy until calcium carbonate all mix), obtain mixture 1;
(ii) mixture 1 and pharmaceutically acceptable carrier are mixed, obtain mixture 2;
(iii) by mixture 2 with contain film coating pre-mix dose
amb(
amb type) solution mix, carry out granulating coatedly, obtain alkali granule;
Described granulates obtains by following method: by citric acid and containing
the alcoholic solution of amb mixes, and carries out wet granulation, obtains granulates.
Described lubricant comprises one or both in Polyethylene Glycol, stearic acid, differential silica gel.
In another preference, step contains described in (iii)
the solution of amb is to contain
the aqueous solution of amb, in the cumulative volume of described aqueous solution, wherein
the concentration of amb is 8%-14%w/v%; More preferably, be 10%-12%w/v%.
In another preference, step is (iii) carried out granulating coated while obtaining alkali granule, and the air intake temperature control of boiling-bed drying is at 60-90 DEG C, and air-out temperature control is at 35-65 DEG C; More preferably, the air intake temperature control of boiling-bed drying is at 70-80 DEG C, and air-out temperature control is at 45-55 DEG C.
In another preference, described in the step of acquisition granulates, contain
the alcoholic solution of amb is in its cumulative volume, wherein
the concentration of amb is 3%-12%w/v%; More preferably, be 5%-8%w/v%.
In another preference, while obtaining the wet granulation of granulates, dry air intake temperature control is at 30-60 DEG C, and temperature of charge is controlled at 20-45 DEG C, and leaving air temp is controlled at 18-42 DEG C; More preferably, dry air intake temperature control is at 40-50 DEG C, and temperature of charge is controlled at 30-35 DEG C, and leaving air temp is controlled at 28-32 DEG C.
In another preference, while obtaining the wet granulation of granulates, granulate order number is 10-30 order, is more preferably 14-20 order, is 16 orders best.
In another preference, described pharmaceutically acceptable carrier comprises disintegrating agent, binding agent, lubricant, correctives and essence.
In another preference, the alkaline foaming agent in described disintegrating agent is selected from sodium bicarbonate, sodium carbonate; Acid foaming agent in described disintegrating agent is selected from fumaric acid, tartaric acid, citric acid, malic acid; Described binding agent is selected from 30 POVIDONE K 30 BP/USP, hydroxypropyl methylcellulose, ethyl cellulose; Described correctives is selected from Aspartane, stevioside, mannitol, xylitol; Described essence is selected from orange taste essence, chrysanthemum taste essence, Mint Essence, vanilla.
In another preference, the incorporation time of described granulates, alkali granule and lubricant is 10-40 minute, is more preferably 15-30 minute.
In a second aspect of the present invention, a kind of calcic effervescent formulation is provided, described effervescent formulation is prepared by following raw material, in the gross weight of raw material, wherein:
30-50% calcium carbonate;
5 μ g-15 μ g vitamin D;
10-29% citric acid;
The pharmaceutically acceptable carrier of 23-65%; With
2%-5%
amb。
In another preference, described effervescent tablet is prepared by following raw material, in the gross weight of raw material, wherein:
30-50% calcium carbonate;
5 μ g-15 μ g vitamin D;
10-29% citric acid;
15-42% sodium bicarbonate;
0.5-2% Polyethylene Glycol;
3-8% fumaric acid;
0.8-3.0% PVP K30;
2-5% essence;
2-5% Aspartane; With
2%-5%
amb。
In another preference, calcic effervescent formulation provided by the invention obtains by preparation method provided by the invention as above.
In another preference, described calcic effervescent formulation is instant effervescent particles, effervescent tablet; More preferably, be effervescent tablet.
In a third aspect of the present invention, a kind of purposes of calcic effervescent formulation provided by the invention as above is provided, as or for the preparation of the compositions of replenishing the calcium.
Accordingly, the invention provides a kind of new calcic effervescent formulation and preparation method thereof.
Detailed description of the invention
Inventor is through extensive and deep research, find in the time preparing calcic effervescent formulation, can be by alkali source and separately preparation of acid source, and in different ways, for example, while preparing alkali source granulating coated by one-step method, in the time preparing acid source, with wet granulation etc., and adopt specific adjuvant, can make product stable in the air, and when preparation in, require low to surrounding.In the time that calcium carbonate and vitamin D are mixed, adopt and wait a point mode equal proportion mixing in addition, can make vitamin D content even.On this basis, completed the present invention.
Calcic effervescent formulation
The invention provides a kind of calcic effervescent formulation, active component wherein comprises calcium carbonate and vitamin D, described calcium carbonate is the calcium carbonate that can be used for making calcium supplementing product well known in the art, preferably include but not limited to high purity medical calcium carbonate, the middle product of calcium raw material of high-compressibility high purity medical calcium carbonate granule or high-density calcium carbonate tablet etc., about " high purity medical calcium carbonate ", " high-compressibility high purity medical calcium carbonate granule " or " product in the middle of the calcium raw material of high-density calcium carbonate tablet " full disclosure in Chinese patent application CN200410052673.8 and CN200910200057.5 respectively, and exquisite detail its preparation method.Content about corresponding calcium carbonate in these published patent applications is all incorporated in the application.Described vitamin D preferred vitamin D
3.In effervescent formulation provided by the invention, also contain pharmaceutically acceptable carrier.
As used herein, term " pharmaceutically acceptable carrier " refers to be used for the treatment of the carrier of agent administration, comprises various excipient and diluent.This term refers to some medicament carriers like this: they itself are not necessary active component, and after using, there is no undue toxicity.Suitable carrier is well known to those of ordinary skill in the art.In Remington ' s Pharmaceutical Sciences (Mack Pub.Co., N.J.1991), can find discussing fully about pharmaceutically acceptable excipient.On combination of Chinese medicine is learned, acceptable carrier can contain liquid, as water, saline, glycerol and ethanol.In addition, in these carriers, also may there is complementary material, as filler, disintegrating agent, lubricant, fluidizer, effervescent, wetting agent or emulsifying agent, correctives, pH buffer substance etc.
Effervescent formulation provided by the invention is prepared by following raw material, in the gross weight of raw material, wherein:
30-50% calcium carbonate;
5 μ g-15 μ g vitamin D;
10-29% citric acid;
The pharmaceutically acceptable carrier of 23-65%; With
2%-5%
amb。
In another preference, described effervescent tablet is prepared by following raw material, in the gross weight of raw material, wherein:
30-50% calcium carbonate;
5 μ g-15 μ g vitamin D;
10-29% citric acid;
15-42% sodium bicarbonate;
0.5-2% Polyethylene Glycol;
3-8% fumaric acid;
0.8-3.0% PVP K30;
2-5% essence;
2-5% Aspartane; With
2%-5%
amb。
Calcic effervescent formulation provided by the invention comprises granule, tablet, preferred tablet.
In one embodiment of the invention, describedly prepared by following raw material containing calcium effervescence tablet, have in every:
Calcium carbonate 1500-2000mg;
Vitamin D5. μ g-15 μ g;
700mg citric acid;
650mg sodium bicarbonate;
30mg Polyethylene Glycol;
150mg fumaric acid;
60mg polyvidone k30; With
120mg
amb。
As used herein, "
amb " refer to film coating pre-mix dose (
amb type), provided by Shanghai Colorcon Coating Technology Co., Ltd.
Preparation method
The preparation method of calcic effervescent formulation provided by the invention is that granulates, alkali granule and mix lubricant are obtained.
Contain calcium effervescence tablet by granulates, alkali granule and mix lubricant if obtain, tabletting obtains.Described lubricant comprises one or both in Polyethylene Glycol, stearic acid, differential silica gel.
The preparation method of described alkali granule is:
The first step, mixes calcium carbonate with vitamin D substep, according to point mode equal proportion mix homogeneously such as quality, guarantee the uniform content of vitamin D in every a slice, obtains mixture 1;
Second step, by mixture 1 and the mixing of pharmaceutically acceptable carrier of mix homogeneously, obtains mixture 2;
The 3rd step, by mixture 2 with contain
the solution of amb mixes, and carries out granulating coatedly, obtains alkali granule.
In the above-mentioned first step, it is that the calcium carbonate of vitamin D homogenous quantities mixes with it that calcium carbonate and vitamin D mix according to point mode equal proportions such as quality, obtain elementary mixture, then use with the calcium carbonate of the quality such as elementary mixture and be mixed to get secondary mixture, by that analogy until calcium carbonate all mix.
The pharmaceutically acceptable carrier using in above-mentioned second step comprises disintegrating agent, binding agent, lubricant, correctives and essence.
Described in above-mentioned the 3rd step, contain
the solution of amb is to contain
the aqueous solution of amb, in the cumulative volume of described aqueous solution, wherein
the concentration of amb is 8%-14%w/v%; Preferably 10%-12%w/v%.
In above-mentioned the 3rd step, carry out granulating coatedly while obtaining alkali granule, the air intake temperature control of boiling-bed drying is at 60-90 DEG C, and air-out temperature control is at 35-65 DEG C.
In a specific embodiment of the present invention, the preparation method of described alkali granule is:
First, calcium carbonate is mixed with vitamin D substep, the calcium carbonate of vitamin D homogenous quantities mixes with it, obtain elementary mixture, then use with the calcium carbonate of the quality such as elementary mixture and be mixed to get secondary mixture, until calcium carbonate all mixes, guarantee the uniform content of vitamin D in every a slice by that analogy, obtain mixture 1;
Secondly, be calcium carbonate vitamin D powder by the mixture 1(of mix homogeneously) fully mix with polyvidone, fumaric acid, sodium bicarbonate, obtain mixture 2;
Finally, mixture 2 is sprayed into and contained
amb coating solution (contains
the aqueous solution of amb, in the cumulative volume of described aqueous solution, wherein
the preferred 10%-12%w/v% of concentration of amb) carry out granulating coated operation, the air intake temperature control of boiling-bed drying is preferably at 70-80 DEG C, and air-out temperature control, preferably at 45-55 DEG C, is made alkali granule.
The preparation method of described granulates is: by citric acid and containing
the alcoholic solution of amb mixes, and carries out wet granulation, obtains granulates.
Described containing
the alcoholic solution of amb is in its cumulative volume, wherein
the concentration of amb is 3%-12%w/v%; Preferably 5%-8%w/v%.
When described wet granulation, dry air intake temperature control is at 30-60 DEG C, and temperature of charge is controlled at 20-45 DEG C, and leaving air temp is controlled at 18-42 DEG C.
In another preference, while obtaining the wet granulation of granulates, granulate order number is 10-30 order, preferably 14-20 order, more preferably 16 orders.
In a specific embodiment of the present invention, the preparation method of described granulates is:
Citric acid is put into wet granulation pot, use dissolve with ethanol solution
amb sprays in pot; Granulate order number is 16 orders, and dry air intake temperature control is preferably at 40-50 DEG C, and temperature of charge is controlled at 30-35 DEG C, and leaving air temp is controlled at 28-32 DEG C.
In a specific embodiment of the present invention, by the granulates preparing by said method of the present invention, alkali granule, put into V-Mixer and mix, after 15-25 minute, add Polyethylene Glycol (degree of polymerization is 4000-6000) to mix 2-10 minute, discharging obtains calcic effervescent formulation; After discharging, tabletting obtains containing calcium effervescence tablet.
In another detailed description of the invention of the present invention, the preparation method of calcium carbonate D3 effervescent tablet provided by the invention comprises the following steps:
A, by calcium carbonate, vitamin D3, sodium bicarbonate, polyvidone, fumaric acid and
amb fully mixes, and is dried through 2-4 hour at 50-60 DEG C, sieves, and becomes alkali granule;
B, by citric acid and
amb wet granulation, granulate, dry, screening, make granulates;
C, by alkali granule, granulates, Polyethylene Glycol mix homogeneously, tabletting, makes.
Wherein, in the time that one-step method is prepared alkali granule, the air intake temperature control of boiling-bed drying is preferably at 70-80 DEG C, and air-out temperature control is preferably at 45-55 DEG C.
When wherein prepared by granulates, adopt wet granulation, ethanol is solvent, and granulate order number is 16 orders, and dry air intake temperature control is preferably at 40-50 DEG C, and temperature of charge is controlled at 30-35 DEG C, and leaving air temp is controlled at 28-32 DEG C.
The mixing of materials time is 15-30 minute.
Purposes
Calcic effervescent formulation provided by the invention is stable in the air non-efflorescing cementitious, meets moment foaming after water, and foaming finishes the transparent calcium beverage of rear generation, can meet human body one day required supplementary calcareous.So calcic effervescent formulation provided by the invention is desirable, easy to carry, the nutrient excellent product rapid, sweet and sour taste of replenishing the calcium, also can be for the preparation of the compositions of replenishing the calcium.The described compositions of replenishing the calcium includes but not limited to, calcium tablet, calcium granule, effervescent tablet, instant effervescent particles.
The above-mentioned feature that the present invention mentions, or the feature that embodiment mentions can combination in any.All features that this case description discloses can with any composition forms use, each feature disclosing in description, can anyly provide the alternative characteristics of identical, impartial or similar object to replace.Therefore apart from special instruction, the feature disclosing is only the general example of equalization or similar features.
Major advantage of the present invention is:
1, after calcic effervescent formulation provided by the invention is met water, calcareous clear solution is rich in formation.
2, calcic effervescent formulation preparation technology provided by the invention is very low for the humidity requirement in space, 60% humidity or more than, still can well produce effervescent tablet and constant product quality.
3, calcic effervescent formulation preparation technology provided by the invention, without low-humidity environment, has reduced cost.
Below in conjunction with specific embodiment, further set forth the present invention.Should be understood that these embodiment are only not used in and limit the scope of the invention for the present invention is described.The experimental technique of unreceipted actual conditions in the following example, the condition of conventionally advising according to normal condition or according to manufacturer.Unless otherwise indicated, otherwise all percent, ratio, ratio or umber by weight.
Unit in percent weight in volume in the present invention is well-known to those skilled in the art, for example, refer to the weight of solute in the solution of 100 milliliters.
Unless otherwise defined, the same meaning that all specialties that use in literary composition and scientific words and one skilled in the art are familiar.In addition, any method similar or impartial to described content and material all can be applicable in the inventive method.The use that better implementation method described in literary composition and material only present a demonstration.
Embodiment 1
The preparation of granulates
Prepare binder solution, by 23.6% weight
amb is dissolved in ethanol, obtains 6.0%
amb alcoholic solution, is controlled at 23 DEG C-27 DEG C by the temperature of this solution, more preferably 25 DEG C before spraying.
Citric acid, fumaric acid are placed in to high-speed mixer, mix 5 minutes.
The acid source mixing is placed in to wet granulation pot, will
amb alcoholic solution carries out wet granulation with the liquid feeding speed of 260ml/min, obtains granulates.
When described wet granulation, dry air intake temperature control is at 45 DEG C, and temperature of charge is controlled at 40 DEG C, and leaving air temp is controlled at 20 DEG C.
In another preference, while obtaining the wet granulation of granulates, granulate order number is 10-30 order, preferably 14-20 order, more preferably 16 orders.
Embodiment 2
The preparation of alkali granule intermediate
Calcium carbonate and vitamin D3 are mixed homogeneously to method mix homogeneously according to equal proportion.
Sodium bicarbonate, essence, aspartame, polyvidone are joined in said mixture material successively, mix 15 minutes.
Said mixture material is poured in boiling-bed drying.
By 65% weight
amb is dissolved in the water, and obtains solid content and be 10%
amb solution.
Carry out one-step method granulation, inlet temperature is controlled at 75 DEG C, and temperature of charge is controlled at 35 DEG C, controlling feed liquor speed is 200ml/min, after in 3 hours, coating solution all having been sprayed, closes air intake heater, blow after 30 minutes with hot blast, obtain the middle product of alkali granule, wherein comprise:
Embodiment 3
Calcium carbonate and vitamin D mix
Calcium carbonate and vitamin D component ratio are as follows:
| Calcium carbonate | 2000 weight portions |
| Vitamin D 3 | 5 -3Weight portion |
In prescription, vitamin D is trace, and calcium carbonate is volume, and the two usage variance is larger, and mix homogeneously is more difficult, adopts two kinds of mixed methods below to compare.
Mixed method 1: the calcium carbonate of recipe quantity is joined in high efficient mixer together with vitamin D, mix.
Mixed method 2: point mode such as quality is mixed, use the calcium carbonate of vitamin D homogenous quantities to mix with it calcium carbonate and vitamin D, obtain elementary mixture, then use with the calcium carbonate of the quality such as elementary mixture and be mixed to get secondary mixture, by that analogy until calcium carbonate all mix.
Two kinds of mixed method comparisons: 1, two kind of material of mixed method directly mixes, and the time used is longer, and is not easy mix homogeneously; Mixed method 2, mixes required time short, and easy mix homogeneously.
Taking the content of vitamin D as investigating index, each incorporation time point detects at 6 different position samples respectively, and the content relative standard deviation (RSD) of the vitamin D of 6 points sees the following form.
| Incorporation time | Mixed method 1 (RSD%) | Mixed method 2 (RSD%) |
| 10 | 43.1 | 14.8 |
| 20 | 40.7 | 13.7 |
| 30 | 34.4 | 10.2 |
| 45 | 32.4 | 10.4 |
| 60 | 26.5 | 10.1 |
In above embodiment, different mixed methods has notable difference to the mixed effect of vitamin D, and mixed method 2 is obviously better than mixed method 1.
Embodiment 4
Preparation is containing calcium effervescence tablet 1
Formula
, weigh as weighing unit according to 10000 of recipe quantity.
By calcium carbonate and vitamin D
3according to equal proportion mix homogeneously method mix homogeneously, then add sodium bicarbonate, essence, aspartame, polyvidone mix homogeneously, pour in boiling-bed drying.Carry out one-step method granulation with coating solution 12% solid content aqueous solution, inlet temperature is controlled at 75 DEG C, and temperature of charge is controlled at 35 DEG C, coutroi velocity and temperature, after coating solution all having been sprayed in 3 hours, close air intake heater, blow after 30 minutes with hot blast, obtain the middle product of alkali granule.
Citric acid, fumaric acid are placed in to wet granulation pot, because of citric acid, fumaric acid good water solubility, are subject to thermally labile, with dissolve with ethanol coating powder, carry out coating granulation.Because citric acid has certain crystal form, so do not need to add a lot of binding agents, only need outer parcel coating.Open sprayer unit, coating solution is evenly sprayed in pot body, the granulation time was controlled at about 7 minutes.After granulation, after 16 order granulate, put into boiling-bed drying, cold wind dries up, and obtains granulates.
Alkali granule and granulates are put into V-Mixer, mix 20 minutes, rotating speed is 10 revs/min, adds the Polyethylene Glycol of recipe quantity to mix 5 minutes, obtains hybrid particles.
Granule is put into tablet machine, and sheet is heavily controlled at 4g, and rotating speed is controlled at 15rpm, and tabletting pressure is controlled at 6kg.
After testing, content meets the requirements this tablet, vitamin D
3the uniformity is good.When disintegration of tablet, be limited to 5 minutes, after effervescent, solution clarification.
Embodiment 5
The preparation of three-layer tablets
Formula
| Material name | Monolithic weighed amount (mg) | Percentage ratio |
| Calcium carbonate | 2000 | 42.15 |
| Vitamin D3 | 0.005 | 0.00 |
| Sodium bicarbonate | 650 | 13.72 |
| Microcrystalline Cellulose | 600 | 12.64 |
| Fumaric acid | 150 | 3.16 |
| Citric acid | 700 | 14.75 |
| Orange taste essence | 200 | 4.21 |
| Aspartame | 150 | 3.16 |
| Polyethylene Glycol | 30 | 0.63 |
| Pulvis Talci | 20 | 0.42 |
| Lactose | 185 | 3.90 |
| Polyvidone | 60 | 1.26 |
| ? | 4745.00 | ? |
By calcium carbonate and vitamin D
3according to equal proportion mix homogeneously method mix homogeneously, add again sodium bicarbonate, microcrystalline Cellulose mix homogeneously, carry out wet granulation using polyvidone 10% solid content aqueous solution as binding agent, inlet temperature is controlled at 75 DEG C, and temperature of charge is controlled at 35 DEG C, coutroi velocity and temperature, after coating solution all having been sprayed in 3 hours, close air intake heater, blow after 30 minutes with hot blast, obtain the middle product of alkali granule, mix homogeneously as ground floor for subsequent use with microcrystalline Cellulose, Pulvis Talci, essence, Aspartane.
Lactose is for subsequent use as the second layer.
Citric acid, fumaric acid are placed in to wet granulation pot, and polyvidone 10% solid content aqueous solution carries out wet granulation as binding agent, obtains granulates, adds microcrystalline Cellulose, Polyethylene Glycol for subsequent use as the 3rd layer.
Ground floor material is put into tablet machine, precompressed; Add the precompressed again of second layer material; Add the 3rd layer of material tabletting and get final product.
Embodiment 6
Coating powder is
iI type
Formula
, weigh as weighing unit according to 10000 of recipe quantity.
By calcium carbonate and vitamin D
3according to equal proportion mix homogeneously method mix homogeneously, then add sodium bicarbonate, essence, aspartame, fumaric acid, polyvidone mix homogeneously, pour in boiling-bed drying.Carry out one-step method granulation with coating solution 12% solid content aqueous solution, inlet temperature is controlled at 75 DEG C, and temperature of charge is controlled at 35 DEG C, coutroi velocity and temperature, after coating solution all having been sprayed in 3 hours, close air intake heater, blow after 30 minutes with hot blast, obtain the middle product of alkali granule.
Citric acid is placed in to wet granulation pot, because of citric acid good water solubility, is subject to thermally labile, with dissolve with ethanol coating powder, carry out coating granulation.Because citric acid has certain crystal form, so do not need to add a lot of binding agents, only need outer parcel coating.Open sprayer unit, coating solution is evenly sprayed in pot body, the granulation time was controlled at about 7 minutes.After granulation, after 16 order granulate, put into boiling-bed drying, cold wind dries up, and obtains granulates.
Alkali granule and granulates are put into V-Mixer, mix 20 minutes, rotating speed is 10 revs/min, adds the Polyethylene Glycol of recipe quantity to mix 5 minutes, obtains hybrid particles.Granule is put into tablet machine, and sheet is heavily controlled at 4g, and rotating speed is controlled at 15rpm, and tabletting pressure is controlled at 6kg.
Embodiment 7
Granulates water preparation coating solution
Formula
, weigh as weighing unit according to 10000 of recipe quantity.
By calcium carbonate and vitamin D
3according to equal proportion mix homogeneously method mix homogeneously, then add sodium bicarbonate, essence, aspartame, fumaric acid, polyvidone mix homogeneously, pour in boiling-bed drying.Carry out one-step method granulation with coating solution 12% solid content aqueous solution, inlet temperature is controlled at 75 DEG C, and temperature of charge is controlled at 35 DEG C, coutroi velocity and temperature, after coating solution all having been sprayed in 3 hours, close air intake heater, blow after 30 minutes with hot blast, obtain the middle product of alkali granule.
Citric acid is placed in to wet granulation pot, because of citric acid good water solubility, is subject to thermally labile, with water dissolution coating powder, carry out coating granulation.Open sprayer unit, coating solution is evenly sprayed in pot body, the granulation time was controlled at about 7 minutes.After granulation, after 16 order granulate, put into boiling-bed drying, cold wind dries up, and obtains granulates.
Alkali granule and granulates are put into V-Mixer, mix 20 minutes, rotating speed is 10 revs/min, adds the Polyethylene Glycol of recipe quantity to mix 5 minutes, obtains hybrid particles.
Granule is put into tablet machine, and sheet is heavily controlled at 4g, and rotating speed is controlled at 15rpm, and tabletting pressure is controlled at 6kg.
Embodiment 8
Preparation method: with embodiment 1.
Test example 1
Embodiment 1-4 products obtained therefrom is detected, effervescent granule exposed 25 DEG C of the temperature that are placed in respectively of preparation, in the environment of relative humidity 60%, place, in 2h, 4h, 8h and sampling in a week, with following index, 4 of above-mentioned acquisition kinds of calcium carbonate effervescing agents are investigated, mainly investigated disintegration time, clarity of solution situation after dissolving, the content situation of placing calcium carbonate and vitamin D after a period of time, the results are shown in Table 1.
Table 1 testing result
| ? | Embodiment 4 | Embodiment 5 | Embodiment 6 | Embodiment 7 | Embodiment 8 |
| Initial disintegration time (min) | 5 | 6 | 5 | 5 | 4 |
| Initial soln situation | Clarification | Clarification | Clarification | Clarification | Clarification |
| Place 2 hours solution situations | Clarification | Clarification | Clarification | Clarification | Clarification |
| Place 4 hours solution situations | Clarification | Clarification | Muddy a little | Muddy a little | Clarification |
| Place 8 hours solution situations | Clarification | Muddy a little | Muddy | Muddy | Clarification |
| Disintegration time (min) after one week | 4 | 8 | 10 | 9 | 5 |
| Solution situation after one week | Muddy a little | Muddy | Serious muddy | Serious muddy | Muddy a little |
| Calcium carbonate content mg after one week | 199.0 | 192 | 162 | 89 | 200.5 |
| Vitamin D content μ g after one week | 5.02 | 4.11 | 3.45 | 3.31 | 4.97 |
Can find out by above testing result, the disintegration time of embodiment 2 is long, and comparison solution moisture absorption after slice, thin piece placement, has affected disintegrate and clarity of solution and vitamin D degraded obviously, due to ground floor and second layer contact need certain hour; Coating powder used in embodiment 3
iI type is non-watertight coating powder, so slice, thin piece was placed after one week, moisture absorption situation is obvious, and granulates and alkali granule have responded; In embodiment 4, in granulates preparation, coating powder is that water is that dissolve medium carries out wet granulation, and in pelletization, dissolving has occurred a part of citric acid, not by coating, so slice, thin piece calcium carbonate in put procedure has occurred to react with citric acid, cause slice, thin piece that significant variation occurs.Embodiment 5 increases the consumption of binding agent within the specific limits, made granule is larger and be not easy to sieve, and the disintegrate situation of slice, thin piece is not affected substantially, increases within the specific limits the consumption of acidic flavoring agent, substantially do not affect slice, thin piece compacting and disintegrate situation, but the taste of solution is had to impact.The preparation method of embodiment 1 effervescent tablet can better be protected calcium carbonate and vitamin D, has extended the period of storage of slice, thin piece.
As everyone knows, effervescent tablet is as a kind of Tabules, responsive especially for moisture, can not be long placed in air.The effervescent tablet that Roche " Redoxon " and the present invention produce is positioned in air simultaneously, and 1 minute rear surface of Redoxon makes moist, air slaking after 2 days.This product can be placed one week, and surface is not any change.
Effervescent tablet of the present invention and " Redoxon " are placed in to water simultaneously, and in 5 minutes, all effervescent finish, and that solution is is transparent, with Fructus Citri sinensis flavor beverage.
The foregoing is only preferred embodiment of the present invention, not in order to limit essence technology contents scope of the present invention, essence technology contents of the present invention is to be broadly defined in the claim scope of application, any technology entity or method that other people complete, if defined identical with the claim scope of application, also or a kind of change of equivalence, be all covered by among this claim scope being regarded as.
Claims (10)
1. a preparation method for calcic effervescent formulation, is characterized in that, described method comprises step: granulates, alkali granule and mix lubricant are obtained to calcic effervescent formulation;
Described alkali granule obtains by following method:
(i) calcium carbonate and vitamin D are mixed according to point mode equal proportions such as quality, obtain mixture 1;
(ii) mixture 1 and pharmaceutically acceptable carrier are mixed, obtain mixture 2;
(iii) by mixture 2 with contain film coating pre-mix dose
amb(
amb type) solution mix, carry out granulating coatedly, obtain alkali granule;
Described granulates obtains by following method: by citric acid and containing
the alcoholic solution of amb mixes, and carries out wet granulation, obtains granulates.
2. preparation method as claimed in claim 1, is characterized in that, step contains described in (iii)
the solution of amb is to contain
the aqueous solution of amb, in the cumulative volume of described aqueous solution, wherein
the concentration of amb is 8%-14%w/v%; Preferably 10%-12%w/v%.
3. preparation method as claimed in claim 1, is characterized in that, step is (iii) carried out granulating coated while obtaining alkali granule, and the air intake temperature control of boiling-bed drying is at 60-90 DEG C, and air-out temperature control is at 35-65 DEG C; The air intake temperature control of boiling-bed drying is preferably at 70-80 DEG C, and air-out temperature control is preferably at 45-55 DEG C.
4. preparation method as claimed in claim 1, is characterized in that, described in the step of acquisition granulates, contains
the alcoholic solution of amb is in its cumulative volume, wherein
the concentration of amb is 3%-12%w/v%; Preferably 5%-8%w/v%.
5. preparation method as claimed in claim 1, is characterized in that, while obtaining the wet granulation of granulates, dry air intake temperature control is at 30-60 DEG C, and temperature of charge is controlled at 20-45 DEG C, and leaving air temp is controlled at 18-42 DEG C; Dry air intake temperature control is preferably at 40-50 DEG C, and temperature of charge control is preferably at 30-35 DEG C, and leaving air temp control is preferably at 28-32 DEG C.
6. preparation method as claimed in claim 1, is characterized in that, described pharmaceutically acceptable carrier comprises disintegrating agent, binding agent, lubricant, correctives and essence.
7. preparation method as claimed in claim 6, is characterized in that, the alkaline foaming agent in described disintegrating agent is selected from sodium bicarbonate, sodium carbonate; Acid foaming agent in described disintegrating agent is selected from fumaric acid, tartaric acid, citric acid, malic acid; Described binding agent is selected from 30 POVIDONE K 30 BP/USP, hydroxypropyl methylcellulose, ethyl cellulose; Described correctives is selected from Aspartane, stevioside, mannitol, xylitol; Described essence is selected from orange taste essence, chrysanthemum taste essence, Mint Essence, vanilla.
8. a calcic effervescent formulation, is characterized in that, described effervescent formulation is prepared by following raw material, in the gross weight of raw material, wherein:
30-50% calcium carbonate;
5 μ g-15 μ g vitamin D;
10-29% citric acid;
The pharmaceutically acceptable carrier of 23-65%; With
2%-5%
amb。
9. calcic effervescent formulation as claimed in claim 8, is characterized in that, described effervescent tablet obtains by preparation method as described in claim 1-7 any one.
10. a purposes for calcic effervescent formulation as claimed in claim 8 or 9, as or for the preparation of the compositions of replenishing the calcium.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201310192774.4A CN104173370B (en) | 2013-05-22 | 2013-05-22 | One kind is containing calcium effervescence tablet and its production and use |
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| CN201310192774.4A CN104173370B (en) | 2013-05-22 | 2013-05-22 | One kind is containing calcium effervescence tablet and its production and use |
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| CN104173370B CN104173370B (en) | 2017-07-25 |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104432065A (en) * | 2014-12-18 | 2015-03-25 | 郑州拓洋生物工程有限公司 | Effervescent tablets with anti-fatigue effect and preparation method of effervescent tablets |
| CN105496983A (en) * | 2016-01-21 | 2016-04-20 | 国药集团汕头金石制药有限公司 | Oyster shell calcium effervescent tablet composition and preparation method thereof |
| CN105640981A (en) * | 2016-01-21 | 2016-06-08 | 国药集团汕头金石制药有限公司 | Oyster calcium carbonate effervescent tablet composition and preparation method thereof |
| CN107875170A (en) * | 2017-11-10 | 2018-04-06 | 江苏扬新生物医药有限公司 | A kind of effervescent agent containing calcium carbonate |
| CN115624125A (en) * | 2022-10-28 | 2023-01-20 | 广州王老吉大健康产业有限公司 | Effervescent tablet and preparation method thereof |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4650669A (en) * | 1985-07-30 | 1987-03-17 | Miles Laboratories, Inc. | Method to make effervescent calcium tablets and calcium tablets produced thereby |
| US20070128272A1 (en) * | 2005-12-07 | 2007-06-07 | Zerbe Horst G | Multi-vitamin and mineral supplement |
| CN102048708A (en) * | 2010-12-08 | 2011-05-11 | 赵磊 | Tinidazole vaginal effervescent tablet and preparation method thereof |
| CN102225070A (en) * | 2011-05-27 | 2011-10-26 | 黄辉 | Calcium carbonate effervescent granule |
| CN102716149A (en) * | 2011-12-22 | 2012-10-10 | 邵爱霞 | Calcium carbonate-D3 effervescent tablet and preparation method thereof |
-
2013
- 2013-05-22 CN CN201310192774.4A patent/CN104173370B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4650669A (en) * | 1985-07-30 | 1987-03-17 | Miles Laboratories, Inc. | Method to make effervescent calcium tablets and calcium tablets produced thereby |
| US20070128272A1 (en) * | 2005-12-07 | 2007-06-07 | Zerbe Horst G | Multi-vitamin and mineral supplement |
| CN102048708A (en) * | 2010-12-08 | 2011-05-11 | 赵磊 | Tinidazole vaginal effervescent tablet and preparation method thereof |
| CN102225070A (en) * | 2011-05-27 | 2011-10-26 | 黄辉 | Calcium carbonate effervescent granule |
| CN102716149A (en) * | 2011-12-22 | 2012-10-10 | 邵爱霞 | Calcium carbonate-D3 effervescent tablet and preparation method thereof |
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104432065A (en) * | 2014-12-18 | 2015-03-25 | 郑州拓洋生物工程有限公司 | Effervescent tablets with anti-fatigue effect and preparation method of effervescent tablets |
| CN105496983A (en) * | 2016-01-21 | 2016-04-20 | 国药集团汕头金石制药有限公司 | Oyster shell calcium effervescent tablet composition and preparation method thereof |
| CN105640981A (en) * | 2016-01-21 | 2016-06-08 | 国药集团汕头金石制药有限公司 | Oyster calcium carbonate effervescent tablet composition and preparation method thereof |
| CN105496983B (en) * | 2016-01-21 | 2018-04-03 | 国药集团汕头金石制药有限公司 | Oyster shell calcium effervescence tablet composition and preparation method thereof |
| CN105640981B (en) * | 2016-01-21 | 2018-09-11 | 国药集团汕头金石制药有限公司 | Oyster shell calcium effervescence tablet composition and preparation method thereof |
| CN107875170A (en) * | 2017-11-10 | 2018-04-06 | 江苏扬新生物医药有限公司 | A kind of effervescent agent containing calcium carbonate |
| CN107875170B (en) * | 2017-11-10 | 2020-07-07 | 江苏扬新生物医药有限公司 | Calcium carbonate-containing effervescent agent |
| CN115624125A (en) * | 2022-10-28 | 2023-01-20 | 广州王老吉大健康产业有限公司 | Effervescent tablet and preparation method thereof |
| CN115624125B (en) * | 2022-10-28 | 2024-03-08 | 广州王老吉大健康产业有限公司 | Effervescent tablet and preparation method thereof |
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| CN104173370B (en) | 2017-07-25 |
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