CN101273973B - Pharmaceutical combination containing Mosapride citrate - Google Patents
Pharmaceutical combination containing Mosapride citrate Download PDFInfo
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- CN101273973B CN101273973B CN200710048739XA CN200710048739A CN101273973B CN 101273973 B CN101273973 B CN 101273973B CN 200710048739X A CN200710048739X A CN 200710048739XA CN 200710048739 A CN200710048739 A CN 200710048739A CN 101273973 B CN101273973 B CN 101273973B
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Abstract
The invention relates to a pharmaceutical composition containing mosapride citrate which is applicable to the usage of direct powder compression for preparation and a preparation method thereof. The pharmaceutical composition further contains a disintegrant, a thinner, a lubricant, a glidant and an adhesive in addition to the active component of the mosapride citrate. The pharmaceutical composition is applicable to the preparation of dispersible tablets which can be fully disintegrated in 2 minutes in water under the temperature of 19 DEG C to 21 DEG C and pass through a No. 2 screen, the hardness is 8 to 11Kg, and the dissolution rate is in line with the relevant provisions, thus solving the problems of higher relevant substances, instable quality and difficult packaging of the mosapride citrate dispersible tablets prepared by wet granulation.
Description
Invention field
The present invention relates to field of pharmaceutical preparations, be in particular a kind of dispersible tablet that contains mosapride citrate.
Background technology
Mosapride citrate, i.e. (±)-4-amino-5-chloro-2-ethyoxyl-N-{[4-(4-luorobenzyl)-2-morpholine] methyl } Benzoylamide citrate dihydrate, third generation medicine for stomach dynamic for Dainippon Pharmaceutical Co., Ltd's exploitation, referring to for example Japan Patent JP3090274, European patent EP 0243959, U.S. Pat 4870074.Mosapride citrate is novel medicine for stomach dynamic, potent selectivity 5-HT4 receptor stimulating agent, make the acetylcholine of teleneuron discharge increase, thereby promote gastric emptying [Katayama K, Morio Y, Haga K, et al.cisapride.a gastroprokinetic agent, bindsto 5-HT4 receptors[J] .Nippon Yakurigaku Zasshi, 1995,105 (6): 461-468.].The clinical chronic gastritis that is used for, functional dyspepsia, the alleviation of a series of gastrointestinal symptoms that reflux esophagitis and operation are followed.[Jinhua, Zhang Tiejun, mosapride citrate---novel medicine for stomach dynamic, pharmacy progress, 2000,24 (5): 306-308].
The dosage form of existing mosapride citrate has 2.5mg, 5mg tablet and 10mg/ bag powder.Use powder that the following restriction and weak point are arranged:
1, uses inconvenience.
2, be difficult for preserving perishable and pollution.
On the other hand, also there is shortcoming in the conventional tablet of mosapride citrate: conventional tablet exists dissolution velocity slow, the shortcoming that dissolubility is little, the influence certain to being absorbed with of medicine.
In the prior art, Chinese patent " the pharmaceutical purpose prescription of mosapride citrate " (CN 01133743.5) discloses the prescription and the preparation method of preparation mosapride citrate dispersible tablet.A large amount of disintegrating agents have been used in this patent formulation, and adopted wet granulation, drying, the preparation method of tabletting, its shortcoming is: at first, prepare mosapride citrate instability in the mosapride citrate dispersible tablet process with this patent, can produce more related substance, under the room temperature condition in the long term store process related substance increase also very fast relatively, product is stable inadequately, for guaranteeing product quality, effect duration can be shorter; Secondly, prepare mosapride citrate dispersible tablet complex technical process with this patent, the production cycle is long, the production cost height; The 3rd, low with the mosapride citrate dispersible tablet hardness of this patent preparation, packaging facilities needs special adaptations could adapt to the requirement of packing.Therefore seek a kind of above shortcoming that can overcome prior art, mosapride citrate can be prepared into and disperse the pharmaceutical composition and the preparation method of sheet to seem extremely important.
Summary of the invention
One aspect of the present invention provides a kind of new pharmaceutical composition that contains mosapride citrate, is in particular a kind of new mosapride citrate dispersible tablet, and it adopts direct powder compression to form; For adapting to technique of direct powder compression, the invention provides the prescription and the ratio of this each component of pharmaceutical composition.
The present invention provides this preparation of drug combination method on the other hand.
Mosapride citrate pharmaceutical composition of the present invention is selected each component of pharmaceutical composition owing to adopting direct powder compression and leading to, and has solved the technical problem that the mosapride citrate dispersible tablet exists in the above-mentioned prior art.
The present invention is by the following technical solutions:
Mosapride citrate is the active component during the present invention fills a prescription.Mosapride citrate can be by for example Japan Patent JP3090274, European patent EP 0243959, the preparation of method described in the U.S. Pat 4870074.
The pharmaceutical composition that contains mosapride citrate that the present invention relates to adopts direct powder compression guaranteeing active substance mosapride citrate steady quality in preparation process and in the long term store process, minimum real estate hydrolysis products estranged, and related substance is controlled.The prescription of suitable preparation dispersible tablet provided by the invention except containing the active component mosapride citrate, also contains disintegrating agent, diluent, lubricant, fluidizer, binding agent.
The ratio of each component of pharmaceutical composition of the present invention is as follows:
Mosapride citrate 1.25-5.0%
Disintegrating agent 2.0-10.0%
Hyprolose 5.0-15.0%
Microcrystalline Cellulose 20.0-45.0%
Lactose 45.0-70.0%
Micropowder silica gel 1.0-3.0%
Magnesium stearate 0.5-2.0%
Preferred version of the present invention is:
Mosapride citrate 1.5-3.5%
Disintegrating agent 2.0-5.0%
Hyprolose 6.0-10.0%
Microcrystalline Cellulose 20.0-30.0%
Lactose 50.0-60.0%
Micropowder silica gel 1.5-2.5%
Magnesium stearate 0.60-1%
The present invention further optimization scheme is:
Mosapride citrate 3.33%
Polyvinylpolypyrrolidone 2.0-5.0%
Hyprolose 6.0-10.0%
Microcrystalline Cellulose 20.0-30.0%
Lactose 50.0-60.0%
Micropowder silica gel 1.5-2.5%
Magnesium stearate 0.60-1.0%
Most preferably scheme of the present invention is:
Mosapride citrate 3.33%
Polyvinylpolypyrrolidone 3.00%
Hyprolose 8.00%
Microcrystalline Cellulose 25.0%
Lactose 57.87%
Micropowder silica gel 2.00%
Magnesium stearate 0.80%
Described disintegrating agent can be selected from crosslinked carboxymethylstach sodium (CCMS-Na), cross-linked carboxymethyl cellulose sodium (CCMC-Na), polyvinylpolypyrrolidone (PVPP).Diluent is the mixture of lactose and microcrystalline Cellulose, and the ratio of lactose and microcrystalline Cellulose is between 1.0-3.5.Binding agent is hyprolose (HPC).Fluidizer is micropowder silica gel.Lubricant is a magnesium stearate.
The preparation method that pharmaceutical composition of the present invention adopts is a direct powder compression, and preparation process is:
(1) get mosapride citrate and cross 120 mesh sieves, hyprolose is crossed 100 mesh sieves, and is standby;
(2) hyprolose and disintegrating agent, microcrystalline Cellulose, lactose, micropowder silica gel, the magnesium stearate of getting after sieving merges, and sieves, and mix homogeneously gets the adjuvant mixture.
(3) get mosapride citrate after sieving, with equivalent progressively increase method and adjuvant mixture mix homogeneously.
(4) measure the mixture content of dispersion, it is heavy to calculate sheet, tabletting, promptly.
Dispersible tablet is meant the rapid homodisperse tablet of disintegrate of energy in water, and according to Chinese Pharmacopoeia 2005 editions, the key parameter of definition dispersible tablet is a dispersing uniformity, requires as follows:
Dispersing uniformity is got 2 of dispersible tablets, puts jolting in the 100ml water, in 20 ℃ ± 1 ℃ water, 3 minutes all disintegrate and by No. 2 the sieve.
The following technical characteristic of dispersible tablet tool that obtains by technical solution of the present invention:
In 19 ℃～21 ℃ water, all disintegrates and in 2 minutes by No. 2 sieves.
Hardness is 8～11Kg.
Below by controlled trial technical scheme of the present invention is described further
One, the selection of adjuvant
(1) selection of disintegrating agent
Can the key parameter of dispersible tablet be their disintegration rates in water, be the hardness of dispersible tablet with the key parameter of ordinary packing equipment package, and selecting suitable disintegrants is most important sport technique segment.Disintegrating agent in the prescription of the present invention has crosslinked carboxymethylstach sodium (CCMS-Na), cross-linked carboxymethyl cellulose sodium (CCMC-Na), polyvinylpolypyrrolidone (PVPP).The content of disintegrating agent is the 2-10% of total formulation weight.
In selection to disintegrating agent, the inventor finds through a large amount of experiments: adopt low-substituted hydroxypropyl cellulose, sodium carboxymethyl cellulose, pregelatinized Starch, Sodium Hydroxymethyl Stalcs, carboxymethylcellulose calcium sodium can not satisfy the requirement of the technical program as single disintegrating agent, have only cross-linked carboxymethyl cellulose sodium, polyvinylpolypyrrolidone, crosslinked carboxymethylstach sodium feasible in prescription as single disintegrating agent.Concrete test situation is as follows:
The present invention adopts prescription: mosapride citrate 3.50%, disintegrating agent 3.00%, microcrystalline Cellulose 25.00%, lactose 57.70%, hyprolose 8.00%, micropowder silica gel 2.00%, magnesium stearate 0.80%, direct powder compression is carried out in employing, and plain sheet hardness is respectively 2-4 kilogram, 5-7 kilogram, 8-11 kilogram.The numbering of disintegrating agent is respectively: 1 low-substituted hydroxypropyl cellulose, 2 sodium carboxymethyl cellulose, 3 pregelatinized Starch, 4 carboxymethyl starch sodium, 5 carboxymethylcellulose calciums, 6 cross-linked carboxymethyl cellulose sodium, 7 polyvinylpolypyrrolidone, 8 crosslinked carboxymethylstach sodium.
Experimental result shows that employing low-substituted hydroxypropyl cellulose, sodium carboxymethyl cellulose, pregelatinized Starch, carboxymethyl starch sodium, carboxymethylcellulose calcium are as disintegrating agent, when the dispersible tablet hardness of compacting is the 2-4 kilogram, disintegration time is in 3 minutes, meet the specification requirement of dispersible tablet, but hardness is too low, is difficult to packing and transportation.And be the dispersible tablet hardness of disintegrating agent preparation when being the 2-4 kilogram with cross-linked carboxymethyl cellulose sodium, polyvinylpolypyrrolidone, crosslinked carboxymethylstach sodium, disintegration time is 60s, when dispersible tablet hardness was the 5-7 kilogram, disintegration time was 80s.Dispersible tablet hardness is during up to the 8-11 kilogram, and disintegration time only is 100s, satisfies the requirement of ordinary packing equipment fully.Concrete data see Table 1:
The disintegration time (dispersed homogeneous degree) of the different disintegrating agent prescriptions of table 1 under different hardness
| Disintegrating agent | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 |
| Hardness 2-4 kilogram | 160s | 175s | 180s | 180s | 180s | 60s | 60s | 60s |
| Hardness 5-7 kilogram | 190s | 200s | 210s | 210s | 210s | 80s | 80s | 80s |
| Hardness 8-11 kilogram | 200s | 210s | 230s | 240s | 250s | 100s | 100s | 100s |
(2) selection of binding agent
The present invention adopts the direct compression preparation method, the selection of binding agent is extremely important, binding agent mainly solves the mouldability and the hardness problem of tablet in prescription, be chosen as hyprolose (HPC) as binding agent in the prescription of the present invention, and its content is the 5-15% of total formulation weight.
The selectable binding agent of preparation dispersible tablet is more, the inventor studies binding agent in the prescription of the present invention, finds polyvidone k30, hypromellose (HPMC), low-substituted hydroxypropyl cellulose, carboxymethyl starch sodium, ethyl cellulose all can not be as binding agent of the present invention.
The inventor has carried out comparative study to hyprolose (HPC) and polyvidone k30, the result shows with polyvidone k30 to be the compositions (prescription 5,6,7) of binding agent, its non-conformity of quality closes the requirement of dispersible tablet, and be the compositions (1,2,3,4) of dry adhesives with hyprolose (HPC), its quality meets the requirement of dispersible tablet fully, in 19 ℃～21 ℃ water, whole disintegrates in 2 minutes are also passed through sieve No. 2.Concrete the results are shown in Table 2 and table 3:
The compositions of table 2 30 POVIDONE K 30 BP/USP 30 and hyprolose
| Component different proportionings | 1 | 2 | 3 | 4 | 5 | 6 | 7 |
| Mosapride citrate | 3.33 | 1.25 | 3.33 | 3.00 | 1.25 | 3.33 | 3.00 |
| Polyvinylpolypyrrolidone | 3.00 | 2.00 | 9.90 | 5.00 | 2.00 | 9.90 | 5.00 |
| Microcrystalline Cellulose | 25.00 | 20.35 | 21.00 | 30.00 | 20.35 | 21.00 | 30.00 |
| Lactose | 57.87 | 69.00 | 54.57 | 45.20 | 69.00 | 54.57 | 45.20 |
| Hyprolose | 8.00 | 5.5 | 8.00 | 14.00 | - | - | - |
| 30 POVIDONE K 30 BP/USP 30 | - | - | - | - | 5.5 | 8.00 | 14.00 |
| Micropowder silica gel | 2.00 | 1.00 | 2.60 | 2.00 | 1.00 | 2.60 | 2.00 |
| Magnesium stearate | 0.80 | 1.90 | 0.60 | 0.80 | 1.90 | 0.60 | 0.80 |
The disintegrate of the composite formula of the different binding agents of table 3 and the situation of relevant nature
| Project the prescription | 1 | 2 | 3 | 4 | 5 | 6 | 7 |
| Mobile | Qualified | Qualified | Qualified | Qualified | Qualified | Qualified | Qualified |
| Compressibility | Qualified | Qualified | Qualified | Qualified | Qualified | Qualified | Qualified |
| Tablet appearance | Qualified | Qualified | Qualified | Qualified | Qualified | Qualified | Qualified |
| Hardness | 8-10 | 8-11 | 8-11 | 8-11 | 6-8 | 6-8 | ＞12 |
| Disintegrate | Qualified | Qualified | Qualified | Qualified | Defective | Defective | Defective |
| Overall merit | Qualified | Qualified | Qualified | Qualified | Defective | Defective | Defective |
The inventor is also to hypromellose (HPMC) simultaneously, low-substituted hydroxypropyl cellulose, carboxymethyl starch sodium, ethyl cellulose as binding agent use in the present invention study, the result shows: the compositions (seeing Table 4) that adopts above different binding agents, adopting hardness respectively is the 2-4 kilogram, hardness is the 5-7 kilogram, hardness is carried out direct compression for the 8-10 kilogram, the character of the tablet that is obtained and the specification requirement of dispersible tablet are relatively, adopt hypromellose, low-substituted hydroxypropyl cellulose, carboxymethyl starch sodium, when the plain sheet hardness of ethyl cellulose prescription is the 2-4 kilogram, meet the requirement of dispersible tablet.When dispersible tablet hardness was the 5-7 kilogram, disintegration time had reached 190-210s, and when dispersible tablet sheet hardness was the 8-10 kilogram, disintegration time was 220-240s, did not meet the specification requirement of dispersible tablet.Concrete data see Table 5:
The compositions of the different binding agents of table 4
| Component different proportionings | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 |
| Mosapride citrate | 1.25 | 3.33 | 1.25 | 3.33 | 1.25 | 3.33 | 1.25 | 3.33 |
| Polyvinylpolypyrrolidone | 2.00 | 9.90 | 2.00 | 9.90 | 2.00 | 9.90 | 2.00 | 9.90 |
| Microcrystalline Cellulose | 20.35 | 21.00 | 20.35 | 21.00 | 20.35 | 21.00 | 20.35 | 21.00 |
| Lactose (mannitol) | 69.00 | 54.57 | 69.00 | 54.57 | 69.00 | 54.57 | 69.00 | 54.57 |
| Hypromellose | 5.5 | 8.00 | - | - | - | - | - | - |
| Low-substituted hydroxypropyl cellulose | - | - | 5.5 | 8.00 | - | - | - | - |
| Component different proportionings | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 |
| Carboxymethyl starch sodium | - | - | - | - | 5.5 | 8.00 | - | - |
| Ethyl cellulose | - | - | - | - | - | - | 5.5 | 8.00 |
| Micropowder silica gel | 1.00 | 2.60 | 1.00 | 2.60 | 1.00 | 2.60 | 1.00 | 2.60 |
| Magnesium stearate | 1.90 | 0.60 | 1.90 | 0.60 | 1.90 | 0.60 | 1.90 | 0.60 |
The disintegration time (dispersed homogeneous degree) of the different adhesive formulas of table 5 under different hardness
| Prescription | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 |
| Hardness 2-4 kilogram | 177s | 175s | 180s | 180s | 180s | 178s | 172s | 180s |
| Hardness 5-7 kilogram | 190s | 200s | 215s | 215s | 220s | 220s | 210s | 210s |
| Hardness 8-10 kilogram | 220s | 2250s | 230s | 230s | 240s | 235s | 230s | 230s |
Above experimental result as can be seen, polyvidone k30, hypromellose (HPMC), low-substituted hydroxypropyl cellulose, carboxymethyl starch sodium, ethyl cellulose can not be as binding agent of the present invention.
(3) selection of diluent
The present invention adopts the direct compression preparation method, therefore the selection of diluent is extremely important, diluent mainly solves the hardness and the disintegrate problem of tablet in prescription, be chosen as lactose (mannitol) and microcrystalline Cellulose as diluent in the prescription of the present invention, lactose (mannitol) has the effect of hydrotropy as soluble component; Microcrystalline cellulose have the effect of certain auxiliary disintegrate.Its content is the 65-90% of total formulation weight.
The selectable diluent of preparation dispersible tablet is more, bibliographical information pregelatinized Starch, starch, calcium sulfate, lactose, mannitol and microcrystalline Cellulose etc. can be as the diluent of dispersible tablet, the inventor tests discovery to above diluent fully as the situation of diluent of the present invention, pregelatinized Starch, starch, calcium sulfate can not have only lactose, mannitol and microcrystalline Cellulose just to can be used as diluent of the present invention as diluent of the present invention.
The present invention is further illustrated by following concrete experiment, adopt the compositions (seeing Table 6) of above different diluent, it is the compositions of diluent that pregelatinized Starch (composite formula 4,6), starch (composite formula 3), calcium sulfate (composite formula 5,7), associating microcrystalline Cellulose, lactose are arranged, its non-conformity of quality closes the requirement of dispersible tablet, shows that pregelatinized Starch, starch, calcium sulfate are not suitable as diluent of the present invention.And adopt microcrystalline Cellulose and lactose (composite formula 1) and adopt microcrystalline Cellulose and mannitol (composite formula 2) to meet the requirement of dispersible tablet fully for its quality of compositions of associating diluent, in 19 ℃～21 ℃ water, whole disintegrates in 2 minutes are also passed through sieve No. 2.It the results are shown in Table 7.
The pharmaceutical composition of the different diluent of table 6
| Component different proportionings | 1 | 2 | 3 | 4 | 5 | 6 | 7 |
| Mosapride citrate | 3.33 | 3.33 | 3.33 | 3.33 | 3.33 | 3.33 | 3.33 |
| Polyvinylpolypyrrolidone | 3.00 | 3.00 | 3.00 | 3.00 | 3.00 | 3.00 | 3.00 |
| Microcrystalline Cellulose | 25.00 | 25.00 | 25.00 | 25.00 | 25.00 | - | - |
| Lactose | 57.87 | - | - | - | - | 25.00 | 25.00 |
| Mannitol | - | 57.87 | - | - | - | - | - |
| Starch | - | - | 57.87 | - | - | - | - |
| Pregelatinized Starch | - | - | - | 57.87 | - | 57.87 | - |
| Calcium sulfate | - | - | - | - | 57.87 | - | 57.87 |
| Hyprolose | 8.00 | 8.00 | 8.00 | 8.00 | 8.00 | 8.00 | 8.00 |
| Micropowder silica gel | 2.00 | 2.00 | 2.00 | 2.00 | 2.00 | 2.00 | 2.00 |
| Magnesium stearate | 0.80 | 0.80 | 0.80 | 0.80 | 0.80 | 0.80 | 0.80 |
The disintegrate of the compositions of the different diluent of table 7 and the situation of relevant nature
| Project the prescription | 1 | 2 | 3 | 4 | 5 | 6 | 7 |
| Mobile | Qualified | Qualified | Defective | Qualified | Defective | Qualified | Defective |
| Compressibility | Qualified | Qualified | Qualified | Qualified | Qualified | Qualified | Qualified |
| Tablet appearance | Qualified | Qualified | Defective | Qualified | Defective | Qualified | Qualified |
| Hardness | 8-11 | 8-11 | 8-11 | 8-11 | 8-10 | 6-8 | ＞12 |
| Disintegrate | Qualified | Qualified | Defective | Defective | Defective | Defective | Defective |
| Overall merit | Qualified | Qualified | Defective | Defective | Defective | Defective | Defective |
Two, the selection of adjuvant ratio
(1) selection of disintegrating agent consumption
The inventor is through concrete experimental studies have found that, prescription in the different components ratio in the table 8 experimentizes, fill a prescription the consumption of 2 disintegrating agents less than 2%, the consumption of prescription 4,6 disintegrating agents is greater than 10%, its non-conformity of quality closes the specification requirement of dispersible tablet, the consumption that shows disintegrating agent is outside the 2-10% scope time, and the prescription of its compositions is not suitable for the present invention; The consumption of the disintegrating agent of prescription 1,3,5,7 is in the 2-10% scope, and its quality meets the requirement of dispersible tablet fully, and in 19 ℃～21 ℃ water, whole disintegrates in 2 minutes are also passed through sieve No. 2, and it the results are shown in Table 9.Disintegrating agent can adopt crosslinked carboxymethylstach sodium (CCMS-Na), cross-linked carboxymethyl cellulose sodium to carry out equivalent for two kinds and replace.It the results are shown in Table 10 and table 11.
The disintegrating agent compositions of table 8 different proportion
| Component different proportionings | 1 | 2 | 3 | 4 | 5 | 6 | 7 |
| Mosapride citrate | 3.33 | 3.33 | 3.33 | 3.33 | 3.33 | 3.33 | 3.33 |
| Polyvinylpolypyrrolidone | 3.00 | 1.50 | 2.00 | 11.00 | 10.00 | 15.00 | 5.00 |
| Microcrystalline Cellulose | 25.00 | 26.50 | 26.00 | 21.00 | 22.00 | 20.00 | 24.00 |
| Lactose | 57.87 | 57.87 | 57.67 | 53.87 | 53.87 | 50.87 | 56.87 |
| Hyprolose | 8.00 | 8.00 | 8.00 | 8.00 | 8.00 | 8.00 | 8.00 |
| Micropowder silica gel | 2.00 | 2.00 | 2.00 | 2.00 | 2.00 | 2.00 | 2.00 |
| Magnesium stearate | 0.80 | 0.80 | 0.8 | 0.80 | 0.80 | 0.80 | 0.80 |
The disintegrate of the different disintegrating agent compositionss of table 9 and the situation of relevant nature
| Project the prescription | 1 | 2 | 3 | 4 | 5 | 6 | 7 |
| Mobile | Qualified | Qualified | Qualified | Qualified | Qualified | Qualified | Qualified |
| Compressibility | Qualified | Qualified | Qualified | Qualified | Qualified | Qualified | Qualified |
| Tablet appearance | Qualified | Qualified | Qualified | Qualified | Qualified | Defective | Qualified |
| Hardness | 8-11 | ＞11 | 8-11 | 5-7 | 8-11 | 6-8 | 8-11 |
| Disintegrate | Qualified | Defective | Qualified | Defective | Qualified | Defective | Qualified |
| Overall merit | Qualified | Defective | Qualified | Defective | Qualified | Defective | Qualified |
Table 10 is the disintegrate of compositions of disintegrating agent and the situation of relevant nature with crosslinked carboxymethylstach sodium
| Project the prescription | 1 | 2 | 3 | 4 | 5 | 6 | 7 |
| Mobile | Qualified | Qualified | Qualified | Qualified | Qualified | Qualified | Qualified |
| Compressibility | Qualified | Qualified | Qualified | Qualified | Qualified | Qualified | Qualified |
| Tablet appearance | Qualified | Qualified | Qualified | Qualified | Qualified | Defective | Qualified |
| Hardness | 8-11 | ＞11 | 8-11 | 5-7 | 8-11 | 6-8 | 8-11 |
| Disintegrate | Qualified | Defective | Qualified | Defective | Qualified | Defective | Qualified |
| Overall merit | Qualified | Defective | Qualified | Defective | Qualified | Defective | Qualified |
Table 11 is the disintegrate of compositions of disintegrating agent and the situation of relevant nature with cross-linked carboxymethyl cellulose sodium
| Project the prescription | 1 | 2 | 3 | 4 | 5 | 6 | 7 |
| Mobile | Qualified | Qualified | Qualified | Qualified | Qualified | Qualified | Qualified |
| Compressibility | Qualified | Qualified | Qualified | Qualified | Qualified | Qualified | Qualified |
| Tablet appearance | Qualified | Qualified | Qualified | Qualified | Qualified | Defective | Qualified |
| Hardness | 8-11 | ＞11 | 8-11 | 5-7 | 8-11 | 6-8 | 8-11 |
| Disintegrate | Qualified | Defective | Qualified | Defective | Qualified | Defective | Qualified |
| Overall merit | Qualified | Defective | Qualified | Defective | Qualified | Defective | Qualified |
(2) selection of binding agent ratio
The inventor is through concrete experimental studies have found that, by experimentizing of the hyprolose compositions of the different proportion in the table 12, the ratio of compositions 4 hyprolose is 4.5, less than 5%, the ratio of compositions 6 hyprolose is 15.5%, the ratio of compositions 7 hyprolose is 17%, greater than 15%, its non-conformity of quality closes the specification requirement of dispersible tablet, and the consumption that shows the binding agent hyprolose is outside the 5-15% scope time, and the prescription of its compositions is not suitable for the present invention; The ratio of compositions 1 hyprolose is 8%, the ratio of compositions 2 hyprolose is 5.5%, the ratio of compositions 3 hyprolose is 5%, the ratio of compositions 5 hyprolose is 15%, all in the 5-15% scope, its quality meets the requirement of dispersible tablet fully, in 19 ℃～21 ℃ water, whole disintegrates in 2 minutes are also passed through sieve No. 2, and it the results are shown in Table 13.Adhesive consumption must be in the 5-15% scope in the prescription of the present invention.
The hyprolose compositions of table 12 different proportion
| Component different proportionings | 1 | 2 | 3 | 4 | 5 | 6 | 7 |
| Mosapride citrate | 3.33 | 3.33 | 3.33 | 3.33 | 3.33 | 3.33 | 3.33 |
| Polyvinylpolypyrrolidone | 3.00 | 2.00 | 3.00 | 3.00 | 8.00 | 8.00 | 9.00 |
| Microcrystalline Cellulose | 25.00 | 25.00 | 21.00 | 25.00 | 25.00 | 25.00 | 22.00 |
| Lactose | 57.87 | 61.37 | 64.87 | 61.37 | 45.87 | 45.37 | 45.87 |
| Hyprolose | 8.00 | 5.50 | 5.00 | 4.50 | 15.00 | 15.50 | 17.00 |
| Micropowder silica gel | 2.00 | 2.00 | 2.00 | 2.00 | 2.00 | 2.00 | 2.00 |
| Magnesium stearate | 0.80 | 0.80 | 0.80 | 0.80 | 0.80 | 0.80 | 0.80 |
The disintegrate of the composite formula of table 13 different proportion hyprolose and the situation of relevant nature
| Project the prescription | 1 | 2 | 3 | 4 | 5 | 6 | 7 |
| Mobile | Qualified | Qualified | Qualified | Qualified | Qualified | Qualified | Qualified |
| Compressibility | Qualified | Qualified | Qualified | Qualified | Qualified | Qualified | Qualified |
| Tablet appearance | Qualified | Qualified | Qualified | Qualified | Qualified | Qualified | Qualified |
| Hardness | 8-10 | 8-11 | 8-11 | 6-8 | 8-11 | 6-8 | ＞12 |
| Disintegrate | Qualified | Qualified | Qualified | Defective | Qualified | Defective | Defective |
| Overall merit | Qualified | Qualified | Qualified | Defective | Qualified | Defective | Defective |
(3) selection of diluent ratio
In the technical program, the selection of diluent ratio is very crucial, in the method that adopts direct powder compression, suitable diluents as the present invention prescription is: contain the two the mixture of 20-45% microcrystalline Cellulose of the lactose of 45-70% of total formulation weight and total formulation weight, and the ratio between diluents microcrystalline cellulose and the lactose is 1.0-3.5.
Come further instruction of the present invention with concrete experiment, compositions with the different proportion of table 14, the ratio of compositions 5 microcrystalline Cellulose and lactose is 7.29, the ratio of compositions 6 microcrystalline Cellulose and lactose is 3.66, the ratio of compositions 7 microcrystalline Cellulose and lactose is 0.6, the ratio of compositions 5,6,7 lactose and microcrystalline Cellulose is outside 1.0-3.5, and its non-conformity of quality closes the requirement of dispersible tablet; The ratio of compositions 1 microcrystalline Cellulose and lactose is 2.31, the ratio of compositions 2 microcrystalline Cellulose and lactose is 3.14, the ratio of compositions 3 microcrystalline Cellulose and lactose is 1, the ratio of compositions 4 microcrystalline Cellulose and lactose is 3.5, effect is preferably arranged that its quality meets the requirement of dispersible tablet fully.This experiment shows: the proportioning of microcrystalline Cellulose and lactose has a proper proportion (1.0-3.5) could satisfy requirement of the present invention, specifically sees Table 15.Lactose in the compositions can adopt mannitol equivalent to replace, and it the results are shown in Table 16.
The lactose of table 14 different proportion and the compositions of microcrystalline Cellulose
| Component different proportionings | 1 | 2 | 3 | 4 | 5 | 6 | 7 |
| Mosapride citrate | 3.33 | 3.33 | 1.25 | 1.25 | 3.33 | 3.33 | 3.33 |
| Polyvinylpolypyrrolidone | 3.00 | 3.00 | 2.00 | 2.00 | 3.00 | 3.00 | 3.00 |
| Microcrystalline Cellulose | 25.00 | 20.00 | 45.00 | 20.00 | 10.00 | 18.00 | 51.00 |
| Lactose | 57.87 | 62.87 | 45.00 | 70.00 | 72.87 | 65.87 | 31.87 |
| Hyprolose | 8.00 | 8.00 | 5.00 | 5.00 | 8.00 | 8.00 | 8.00 |
| Micropowder silica gel | 2.00 | 2.00 | 1.00 | 1.00 | 2.00 | 2.00 | 2.00 |
| Magnesium stearate | 0.80 | 0.80 | 0.75 | 0.75 | 0.80 | 0.80 | 0.80 |
The disintegrate of table 15 different proportion compositions and the situation of relevant nature
| Project the prescription | 1 | 2 | 3 | 4 | 5 | 6 | 7 |
| Mobile | Qualified | Qualified | Qualified | Qualified | Defective | Defective | Qualified |
| Compressibility | Qualified | Qualified | Qualified | Qualified | Qualified | Qualified | Qualified |
| Tablet appearance | Qualified | Qualified | Qualified | Qualified | Qualified | Qualified | Qualified |
| Hardness | 8-11 | 8-11 | 8-11 | 8-11 | 4-6 | 4-6 | ＞12 |
| Disintegrate | Qualified | Qualified | Qualified | Qualified | Defective | Defective | Defective |
| Overall merit | Qualified | Qualified | Qualified | Qualified | Defective | Defective | Defective |
Table 16 contains the disintegrate of different proportion mannitol compositions and the situation of relevant nature
| Project the prescription | 1 | 2 | 3 | 4 | 5 | 6 | 7 |
| Mobile | Qualified | Qualified | Qualified | Qualified | Defective | Defective | Qualified |
| Compressibility | Qualified | Qualified | Qualified | Qualified | Qualified | Qualified | Qualified |
| Tablet appearance | Qualified | Qualified | Qualified | Qualified | Qualified | Qualified | Qualified |
| Hardness | 8-11 | 8-11 | 8-11 | 8-11 | 4-6 | 4-6 | ＞12 |
| Disintegrate | Qualified | Qualified | Qualified | Qualified | Defective | Defective | Defective |
| Overall merit | Qualified | Qualified | Qualified | Qualified | Defective | Defective | Defective |
By above specific description as can be seen, the present invention has obtained better effects to a large amount of research of process of the kind and the ratio of disintegrating agent, binding agent, diluent.
Beneficial effect of the present invention:
1, solved the higher problem of related substance: adopt wet granule compression tablet, need add binding agent system soft material, binding agent contains a large amount of water, and again through high temperature drying, the related substance increase is bigger.The present invention adopts direct powder compression, and by the selection to adjuvant and ratio thereof, has successfully solved the related substance stability problem.
2, solve the difficult problem of packing: with respect to mosapride citrate wet granulation in the prior art, the equipment that technical scheme of the present invention is used is the sheeting equipment of general ordinary tablet, do not need facility for granulating and drying equipment, with short production cycle, the relative wet method granule of production cost tabletting is low.The slice, thin piece hardness of being pressed is at 8-11Kg, and is suitable with the hardness of ordinary tablet, and it is not enough to solve general dispersible tablet hardness, the problem of packing difficulty.The present invention successfully solves the problem that adopts common packer packing dispersible tablet.
For investigating wet granule compression tablet and direct powder compression preparation in the influence of hot and humid condition to related substance, the inventor has carried out comparative study, and concrete experimental result is as follows:
Reference embodiment 1:
Experimental technique: composite formula is as follows:
Mosapride citrate 3%
Starch 10%
Lactose 48%
Microcrystalline Cellulose 17%
Low-substituted hydroxypropyl cellulose 17%
Hypromellose 1.3%
Magnesium stearate 0.7%
Micropowder silica gel 3%
Adopt the preparation method of wet granule compression tablet as follows:
The active component mosapride citrate is crossed 180 mesh sieves, and it is standby that all adjuvants are crossed 120 mesh sieves.
1. take by weighing starch, lactose, microcrystalline Cellulose and the disintegrating agent of formula ratio, with suitable blender mix homogeneously.
2. take by weighing the mosapride citrate of above formula ratio, it is added in the mixed accessories with the equivalent dilution method that progressively increases, fully mixed 40 mesh sieves at every turn until complete mix homogeneously.
3. prepare soft material with 2%HPMC40% ethanol liquid, 18 mesh sieve system wet granulars.
4. will go up a gained wet granular in 60 ℃ of aeration-dryings, 2 hours taking-up back 18 mesh sieve granulate.
5. take by weighing above formula ratio micropowder silica gel and magnesium stearate and mix a upward granule, fully mixing.
6. on tablet machine, use 8mm punching press system, promptly.
The dispersible tablet tool following properties that obtains:
In 19 ℃～21 ℃ water, whole disintegrates in 3 minutes are also passed through sieve No. 2.
Hardness is 5～7Kg.
Dissolution is up to specification
With identical mosapride citrate raw material, adopt the dispersible tablet of 1 two kinds of different preparation method preparations of reference embodiment 1 and embodiments of the invention, its related substance has bigger difference, the related substance of wet method preparation exceeds the dry formulations preparation more than 2 times, concrete data see Table 17, and the difference of two kinds of preparation maximums is exactly the hot and humid condition that adopted in the preparation process of wet method preparation.
Dispersible tablet to two kinds of different preparation method preparations carries out hot and humid accelerated test simultaneously, and method is as follows:
1. the hot conditions sample was put in 600 calorstats, respectively at the 5th, 10 day sampling and measuring.
2. the super-humid conditions sample was put under 92.5% damp condition, in the 5th, 10 day sampling and measuring.
Related substance, Determination on content method:
Related substance is got this product fine powder an amount of (being equivalent to mosapride citrate 5mg approximately), puts in the 25ml volumetric flask, adds the 15ml that makes an appointment that flows, jolting makes the mosapride citrate dissolving, and is diluted to scale with mobile phase, shakes up, filter, get subsequent filtrate as need testing solution.Precision is measured 2ml, puts in the 100ml volumetric flask, adds mobile phase and is diluted to scale, shakes up, in contrast solution.Measuring according to high performance liquid chromatography (2005 editions two appendix V D of Chinese Pharmacopoeia), is filler with octadecylsilane chemically bonded silica; (regulating pH value to 4.0 with sodium hydroxide test solution)-acetonitrile (70: 30) is a mobile phase with the 0.05mol/L citric acid soln; The detection wavelength is 274nm.Theoretical pedal number calculates by the mosapride citrate peak and is not less than 2000.Get contrast solution 10ul and inject chromatograph of liquid, regulate detection sensitivity, make the peak height of main constituent chromatographic peak be about 20% of full scale, precision is measured need testing solution and each 10ul of contrast solution again, inject chromatograph of liquid respectively, the record chromatogram is to 2 times of main constituent peak retention time.In the chromatogram of need testing solution if any impurity peaks, the deduction with the main peak relative retention time less than 0.20 chromatographic peak after, single impurity peak area must not be greater than 1/2 of contrast solution main peak area, each impurity peak area and must not be greater than the contrast solution peak area.
It is an amount of that assay is got this product, and accurate the title decided porphyrize, precision takes by weighing in right amount (being equivalent to mosapride citrate 5mg approximately), puts in the 50ml volumetric flask, and it is an amount of to add ethanol, supersound process 15 minutes makes mosapride citrate dissolving, and with ethanol dilution to scale, shake up, filter, precision is measured subsequent filtrate 5ml, puts in the 25ml volumetric flask, add ethanol dilution to scale, shake up; Measure absorption value at 274nm wavelength place according to ultraviolet visible spectrophotometry (two appendix IV of Chinese Pharmacopoeia version in 2005 A); It is an amount of that precision takes by weighing the mosapride citrate reference substance in addition, adds the solution that ethanol is made 20ug/ml, measures with method, calculates, promptly.
The related substance of wet method preparation exceeds the dry formulations preparation more than 2 times, and after 10 days, the related substance of wet method preparation exceeds dry formulations more than 1 times, sees Table 17 in the high-temperature factor condition; After 10 days, the related substance of wet method preparation exceeds the dry formulations preparation more than 2 times, sees Table 18 in high humidity factor condition.From table 17 and 18 as can be seen, hot and humid influence to related substance is bigger, so employing dry formulations, avoided hot and humid condition, well solved the higher difficult problem of related substance, the increase of the related substance of the preparation of employing direct powder compression has significant difference much smaller than wet granule compression tablet.
Simultaneously, also can obtain and should demonstrate,prove from the data that long-time stability are tested related substance, the long-time stability experiment that wet granule compression tablet and direct powder compression make preparation shows that the increase situation of related substance sees Table 19:
Table 17 high-temperature factor experimental result
Table 18 high humidity factor experimental result
Table 19 long-time stability experimental result
As can be seen, the present invention has successfully solved the situation that related substance significantly increases, and the quality of the pharmaceutical preparations that adopts case of the present invention to obtain is more reliable and more stable.
The specific embodiment
Below by embodiment the present invention is further described, but should not be considered as any restriction that the present invention is made.
Embodiment 1 to 7, sees Table 20:(and calculates by weight)
Table 20 embodiment 1 to 7
| Component different proportionings | 1 | 2 | 3 | 4 | 5 | 6 | 7 |
| Mosapride citrate | 3.33 | 3.33 | 1.25 | 3.33 | 5.00 | 1.25 | 3.00 |
| Polyvinylpolypyrrolidone | 3.00 | 2.20 | 2.00 | 9.90 | 4.00 | 2.00 | 5.00 |
| Microcrystalline Cellulose | 25.00 | 25.00 | 20.35 | 21.00 | 21.00 | 45.00 | 30.00 |
| Lactose | 57.87 | 57.87 | 69.00 | 54.57 | 52.00 | 45.00 | 45.20 |
| Hyprolose | 8.00 | 8.00 | 5.5 | 8.00 | 14.50 | 5.00 | 14.00 |
| Micropowder silica gel | 2.00 | 2.80 | 1.00 | 2.60 | 2.50 | 1.00 | 2.00 |
| Magnesium stearate | 0.80 | 0.80 | 1.90 | 0.60 | 1.00 | 0.75 | 0.80 |
The preparation method of above embodiment:
The direct powder compression that adopts, its preparation process is:
(1) get mosapride citrate and cross 120 mesh sieves, hyprolose is crossed 100 mesh sieves, and is standby;
(2) hyprolose and polyvinylpolypyrrolidone, microcrystalline Cellulose, lactose, micropowder silica gel, the magnesium stearate of getting after sieving merges, and sieves, and mix homogeneously gets the adjuvant mixture.
(3) get mosapride citrate after sieving, with equivalent progressively increase method and adjuvant mixture mix homogeneously.
(4) measure the mixture content of dispersion, it is heavy to calculate sheet, tabletting, promptly.
The dispersible tablet tool following properties that obtains:
In 19 ℃～21 ℃ water, whole disintegrates in 2 minutes are also passed through sieve No. 2.
Hardness is 8～11Kg.
Dissolution is up to specification
Embodiment 8 to 14, see Table 21:(and calculate by weight)
Table 21 embodiment 8 to 14
| Component different proportionings | 8 | 9 | 10 | 11 | 12 | 13 | 14 |
| Mosapride citrate | 3.33 | 3.33 | 1.25 | 1.50 | 5.00 | 3.50 | 3.00 |
| Crosslinked carboxymethylstach sodium | 3.00 | 2.20 | 2.00 | 9.90 | 4.00 | 5.00 | 5.00 |
| Microcrystalline Cellulose | 25.00 | 25.00 | 20.00 | 20.00 | 21.00 | 39.50 | 30.00 |
| Component different proportionings | 8 | 9 | 10 | 11 | 12 | 13 | 14 |
| Lactose | 57.87 | 57.87 | 70.00 | 59.50 | 52.00 | 45.00 | 49.20 |
| Hyprolose | 8.00 | 8.00 | 4.85 | 6.00 | 14.50 | 5.00 | 10.00 |
| Micropowder silica gel | 2.00 | 2.80 | 1.00 | 2.50 | 2.50 | 1.50 | 2.00 |
| Magnesium stearate | 0.80 | 0.80 | 1.90 | 0.60 | 1.00 | 0.50 | 0.80 |
The preparation method of above embodiment:
Adopt direct powder compression, its preparation process is:
(1) get mosapride citrate and cross 120 mesh sieves, hyprolose is crossed 100 mesh sieves, and is standby;
(2) hyprolose and crosslinked carboxymethylstach sodium, microcrystalline Cellulose, lactose, micropowder silica gel, the magnesium stearate of getting after sieving merges, and sieves, and mix homogeneously gets the adjuvant mixture.
(3) get mosapride citrate after sieving, with equivalent progressively increase method and adjuvant mixture mix homogeneously.
(4) measure the mixture content of dispersion, it is heavy to calculate sheet, tabletting, promptly.
The dispersible tablet tool following properties that obtains:
In 19 ℃～21 ℃ water, whole disintegrates in 2 minutes are also passed through sieve No. 2.
Hardness is 8～11Kg.
Dissolution is up to specification
Embodiment 15 to 21, see Table 22:(and calculate by weight)
Table 22 embodiment 15 to 21
| Component different proportionings | 15 | 16 | 17 | 18 | 19 | 20 | 21 |
| Mosapride citrate | 3.33 | 3.33 | 1.25 | 3.33 | 5.00 | 1.25 | 3.00 |
| Cross-linked carboxymethyl cellulose sodium | 3.00 | 2.20 | 2.00 | 9.90 | 4.00 | 2.00 | 5.00 |
| Microcrystalline Cellulose | 25.00 | 25.00 | 45.00 | 21.00 | 21.00 | 45.00 | 30.00 |
| Lactose | 57.87 | 57.87 | 45.00 | 54.57 | 52.00 | 45.00 | 45.20 |
| Hyprolose | 8.00 | 8.00 | 4.85 | 8.00 | 14.50 | 5.00 | 14.00 |
| Micropowder silica gel | 2.00 | 2.80 | 1.00 | 2.60 | 2.50 | 1.00 | 2.00 |
| Magnesium stearate | 0.80 | 0.80 | 1.90 | 0.60 | 1.00 | 0.75 | 0.80 |
The preparation method of above embodiment:
Adopt direct powder compression, its preparation process is:
(1) get mosapride citrate and cross 120 mesh sieves, hyprolose is crossed 100 mesh sieves, and is standby;
(2) hyprolose and cross-linked carboxymethyl cellulose sodium, microcrystalline Cellulose, lactose, micropowder silica gel, the magnesium stearate of getting after sieving merges, and sieves, and mix homogeneously gets the adjuvant mixture.
(3) get mosapride citrate after sieving, with equivalent progressively increase method and adjuvant mixture mix homogeneously.
(4) measure the mixture content of dispersion, it is heavy to calculate sheet, tabletting, promptly.
The dispersible tablet tool following properties that obtains:
In 19 ℃～21 ℃ water, whole disintegrates in 2 minutes are also passed through sieve No. 2.
Hardness is 8～11Kg.
Dissolution is up to specification
Embodiment 22 to 28, see Table 23:(and calculate by weight)
Table 23 embodiment 22 to 28
| Component different proportionings | 22 | 23 | 24 | 25 | 26 | 27 | 28 |
| Mosapride citrate | 3.33 | 3.33 | 1.25 | 3.33 | 5.00 | 1.25 | 3.00 |
| Polyvinylpolypyrrolidone | 3.00 | 2.20 | 2.00 | 9.90 | 4.00 | 2.00 | 5.00 |
| Microcrystalline Cellulose | 25.00 | 25.00 | 20.35 | 21.00 | 21.00 | 45.00 | 30.00 |
| Mannitol | 57.87 | 57.87 | 69.00 | 54.57 | 52.00 | 45.00 | 45.20 |
| Hyprolose | 8.00 | 8.00 | 5.5 | 8.00 | 14.50 | 5.00 | 14.00 |
| Micropowder silica gel | 2.00 | 2.80 | 1.00 | 2.60 | 2.50 | 1.00 | 2.00 |
| Magnesium stearate | 0.80 | 0.80 | 1.90 | 0.60 | 1.00 | 0.75 | 0.80 |
The preparation method of above embodiment:
Adopt direct powder compression, its preparation process is:
(1) get mosapride citrate and cross 120 mesh sieves, hyprolose is crossed 100 mesh sieves, and is standby;
(2) hyprolose and polyvinylpolypyrrolidone, microcrystalline Cellulose, mannitol, micropowder silica gel, the magnesium stearate of getting after sieving merges, and sieves, and mix homogeneously gets the adjuvant mixture.
(3) get mosapride citrate after sieving, with equivalent progressively increase method and adjuvant mixture mix homogeneously.
(4) measure the mixture content of dispersion, it is heavy to calculate sheet, tabletting, promptly.
The dispersible tablet tool following properties that obtains:
In 19 ℃～21 ℃ water, whole disintegrates in 2 minutes are also passed through sieve No. 2.
Hardness is 8～11Kg.
Dissolution is up to specification.
Claims (4)
1. a dispersible tablet that contains mosapride citrate is characterized in that, this dispersible tablet is to be made by following raw materials by weight percent:
Mosapride citrate 1.25-5.0%
Disintegrating agent 2.0-10.0%
Hyprolose 5.0-15.0%
Microcrystalline Cellulose 20.0-45.0%
Lactose 45.0-70.0%
Micropowder silica gel 1.0-3.0%
Magnesium stearate 0.5-2.0%
Described disintegrating agent is selected from polyvinylpolypyrrolidone, crosslinked carboxymethylstach sodium or cross-linked carboxymethyl cellulose sodium; The part by weight of lactose and microcrystalline Cellulose is between 1.0-3.5;
The preparation method of this dispersible tablet is crossed 120 mesh sieves for getting mosapride citrate, and it is standby that hyprolose is crossed 100 mesh sieves; Get sieve back formula ratio hyprolose and formula ratio disintegrating agent, microcrystalline Cellulose, lactose, micropowder silica gel, magnesium stearate merges, and sieves, mix homogeneously must the adjuvant mixture; Get the back formula ratio mosapride citrate that sieves, with equivalent progressively increase method and adjuvant mixture mix homogeneously; Measure the mixture content of dispersion, it is heavy to calculate sheet, tabletting, and hardness is 8～11Kg, promptly.
2. the dispersible tablet that contains mosapride citrate according to claim 1, the percentage by weight of wherein said raw material is:
Mosapride citrate 1.5-3.5%
Disintegrating agent 2.0-5.0%
Hyprolose 6.0-10.0%
Microcrystalline Cellulose 20.0-30.0%
Lactose 50.0-60.0%
Micropowder silica gel 1.5-2.5%
Magnesium stearate 0.60-1.0%.
3. the dispersible tablet that contains mosapride citrate according to claim 2, the percentage by weight of wherein said raw material is:
Mosapride citrate 3.33%
Disintegrating agent 2.0-5.0%
Hyprolose 6.0-10.0%
Microcrystalline Cellulose 20.0-30.0%
Lactose 50.0-60.0%
Micropowder silica gel 1.5-2.5%
Magnesium stearate 0.60-1.0%.
4. the dispersible tablet that contains the citric acid mosapride according to claim 3, the percentage by weight of wherein said raw material is:
Mosapride citrate 3.33%
Polyvinylpolypyrrolidone 3.00%
Hyprolose 8.00%
Microcrystalline Cellulose 25.0%
Lactose 57.87%
Micropowder silica gel 2.00%
Magnesium stearate 0.80%.
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| CN102335154B (en) * | 2010-07-28 | 2014-08-06 | 重庆健能医药开发有限公司 | Mosapride citrate sustained-release tablet |
| CN102600091B (en) * | 2012-02-13 | 2014-01-29 | 迪沙药业集团有限公司 | Itopride hydrochloride dispersible tablet composition |
| CN105560249B (en) * | 2014-10-10 | 2019-07-16 | 成都康弘药业集团股份有限公司 | A kind of pharmaceutical composition containing mosapride citrate |
| CN105769872B (en) * | 2014-12-25 | 2019-05-03 | 成都康弘药业集团股份有限公司 | A kind of mosapride citrate composition of Fast Stripping |
| CN107661506B (en) * | 2016-07-26 | 2022-04-29 | 江苏豪森药业集团有限公司 | Mosapride citrate pharmaceutical preparation and preparation method thereof |
| CN107397731A (en) * | 2017-07-25 | 2017-11-28 | 重庆多普泰制药股份有限公司 | A kind of Maixuekang plain piece, enteric coated tablet and preparation method thereof |
| CN107744509B (en) * | 2017-10-24 | 2020-06-12 | 浙江昂利康制药股份有限公司 | Mosapride citrate tablet and preparation method thereof |
| CN109745293B (en) * | 2017-11-08 | 2021-09-07 | 成都康弘药业集团股份有限公司 | Pharmaceutical composition containing mosapride citrate |
| CN111281875A (en) * | 2018-12-07 | 2020-06-16 | 成都康弘药业集团股份有限公司 | Composition containing mosapride citrate and preparation method thereof |
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| CN1359680A (en) * | 2001-12-26 | 2002-07-24 | 成都康弘制药有限公司 | Prescription of preparing moxapride citrate |
| CN1911233A (en) * | 2005-08-11 | 2007-02-14 | 鲁南制药集团股份有限公司 | Medicine composite contg. Moxabilli and antioxidant |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN1359680A (en) * | 2001-12-26 | 2002-07-24 | 成都康弘制药有限公司 | Prescription of preparing moxapride citrate |
| CN1911233A (en) * | 2005-08-11 | 2007-02-14 | 鲁南制药集团股份有限公司 | Medicine composite contg. Moxabilli and antioxidant |
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