CN105560249A - Pharmaceutical composition containing mosapride citrate - Google Patents
Pharmaceutical composition containing mosapride citrate Download PDFInfo
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Abstract
The invention relates to a pharmaceutical composition containing mosapride citrate. The pharmaceutical composition contains lactose and other pharmaceutically acceptable accessory materials. Through strict control of a mass ratio of lactose to water in the pharmaceutical composition, mosapride citrate long-term storage stability is greatly improved and related substance generation and increasing risk is reduced. The pharmaceutical composition provides guarantee for clinical drug safety and effectiveness.
Description
Technical field
The invention belongs to field of pharmaceutical preparations, be specifically related to a kind of pharmaceutical composition containing mosapride citrate.
Background technology
Mosapride citrate (MosaprideCitrate) is a kind of selectivity 5-HT
4receptor stimulating agent, belongs to third generation medicine for stomach dynamic, is mainly used in treatment functional dyspepsia (FD) and gastroesophageal reflux disease.This medicine obviously can improve the turning sour of FD patient, the symptom such as heartburn, and can accelerate gastric emptying, promotes stomach and uodenal movement.The mosapride citrate preparation gone on the market at present is more, as the import drugs " JIASIQING " produced by Yuan Yan company SUMITOMO CHEMICAL Pharmaceutical, Dispersible Mosapride citrate tablets " new network is received " that the Mosapride Citrate Tablets " fast power " of domestic imitation enterprise composite tablet pharmaceutical manufacturing, Kang Hong Pharmaceutical are produced etc.Oral solid formulation enters after in body, all needs to be absorbed by body through biomembrane through process in leaching.Specify in existing national standards WSI-(X-287)-2003Z, in 0.1mol/L hydrochloric acid solution, Mosapride Citrate Tablets is not less than 75% at 30min dissolution; Import drugs registered standard JX20080288 is defined in the phosphate buffered saline(PBS) of pH6.8, and mosapride citrate 45min dissolution is not less than 80%.But, because mosapride citrate is insoluble drug, water-soluble hardly, in the actual production of Mosapride citrate oral solid preparation, often run into the low even underproof problem of dissolution.
Lactose (lactose) is as a kind of conventional adjuvant, and be extensively used as filler and the diluent of Mosapride Citrate Tablets agent and capsule, have compact property better, the surface-brightening of the tablet be pressed into is attractive in appearance, and tablet hardness is larger.Tablet hardness can not only be improved with the Mosapride Citrate Tablets agent that lactose is adjuvant, increase anti-wear performance, smooth appearance is fine and smooth, but also can improve inherence " stripping " performance to a certain extent, especially insoluble drug is had to the effect promoting bioavailability in body.All containing lactose in many mosapride citrate preparations at present, such as: in former triturate " JIASIQING " prescription disclosed in SUMITOMO CHEMICAL Pharmaceutical, namely have employed lactose (pharmaceuticals イ Application タ ビ ュ ー フ ォ ー system, Japan specialized hospital medicine drug Division can be Yaoed Collar 2008 To Quasi Bases て and is made by IF Ji Load, in May, 2012 (changing Order the 20th edition), Japanese Standard Quasi commodity divide Class designation 872399); Chinese patent ZL200510090146.0 discloses a kind of Dispersible Mosapride citrate tablets containing lactose; Chinese patent application 201410266842.1 provides a kind of Mosapride Citrate Tablets and preparation method thereof, and in its prescription, lactose content reaches 40%-75%.
But, the applicant finds in long-term production practices, although the mosapride citrate preparation containing lactose can improve drug-eluting performance to a certain extent, but there is the phenomenon that dissolution obviously declines in medicine after long term storage, and its related substances significantly rises in preparation, safety and the effective performance of drug bring control unknown risks.
Summary of the invention
Unstable in order to solve existing mosapride citrate preparation long term storage, the problems such as dissolution reduction, related substance increase, the invention provides a kind of pharmaceutical composition containing mosapride citrate, containing lactose and other pharmaceutically acceptable adjuvants in described pharmaceutical composition, mass ratio >=19.0 of lactose and water in described pharmaceutical composition, preferably >=54.2, most preferably >=60.0; Wherein, described lactose is Lactis Anhydrous;
Further, in described pharmaceutical composition, other pharmaceutically acceptable adjuvants are selected from one or more in disintegrating agent, lubricant, fluidizer; Wherein, disintegrating agent be selected from microcrystalline Cellulose, cross-linked carboxymethyl cellulose sodium, polyvinylpolypyrrolidone, low-substituted hydroxypropyl cellulose, sodium carboxymethylcellulose pyce one or more, be preferably in low-substituted hydroxypropyl cellulose, microcrystalline Cellulose, polyvinylpolypyrrolidone one or more; Lubricant be selected from glyceryl palmitostearate, Glyceryl Behenate, glyceryl monostearate, stearic acid, magnesium stearate one or more; Fluidizer is one or more in Pulvis Talci, micropowder silica gel, is preferably micropowder silica gel;
Preferably, in described pharmaceutical composition, the mass percent of each component is: mosapride citrate 1.42%-11.11%, lactose 44.12%-59.52%, disintegrating agent 31.11%-52.06%, lubricant 0.44%-1.69%, fluidizer 1.91%-2.73%; Preferably, in described pharmaceutical composition, the mass percent of each component is: mosapride citrate 3.36%, lactose 57.72%, disintegrating agent 35.57%, fluidizer 2.01%, lubricant 1.34%;
The present invention further provides the preparation method of the described pharmaceutical composition containing mosapride citrate, concrete steps are: by lactose and other pharmaceutically acceptable adjuvant dryings, then under the condition of ambient humidity≤60%RH, mosapride citrate is even with lactose, disintegrating agent, fluidizer and mix lubricant successively, and tabletting, encapsulated or fill become powder; Preferably, described lactose and other pharmaceutically acceptable adjuvants vacuum drying 30-60min at 60 DEG C, described ambient humidity≤45%RH.
Applicant finds, under lactose and the simultaneous situation of water, mosapride citrate extended storage stability obviously reduces, and causes its related substances to increase, and mosapride citrate dissolution significantly declines.Applicant be experimental studies have found that by a large amount of, strict control contains the mass ratio of lactose and water in the pharmaceutical composition of mosapride citrate, effectively can overcome pharmaceutical composition defect such as dissolution reduction, its related substances rising after long term storage, substantially increase the long-time stability of medicine, for the quality and safety of medicine and effectiveness provide guarantee.
Be described further below by part Experiment content, the present invention institute is experimentally as follows with material:
1, related substance detection method
Sample thief powder (amounting to mosapride citrate 10mg), add water 1mL, adds methanol 9mL, jolting 20 minutes, centrifugal, gets supernatant as need testing solution;
Precision measures above-mentioned need testing solution 1mL, puts in 20mL measuring bottle, with methanol dilution to scale; Shake up, precision measures the need testing solution 2mL after dilution, puts in 20mL measuring bottle, with methanol dilution to scale, shakes up, in contrast solution.
Measure according to high performance liquid chromatography (Chinese Pharmacopoeia version in 2010 two annex V D).(sodium citrate dihydrate 8.82g is got with liquor sodii citratis, the 800mL that adds water dissolves, by dilute hydrochloric acid adjust ph to 4.0, add water to 1000mL) as mobile phase A, acetonitrile, as Mobile phase B, carries out gradient elution, in 0-40min, mobile phase A is by 85%-45%, and Mobile phase B is by 15%-55%; HypersilGOLDC18 chromatographic column (Thermo, 15*4.6mm, 5 μm); Determined wavelength is 274nm; Column temperature is 40 DEG C, and flow velocity is 1mL/min; Sample size is 10 μ l.Number of theoretical plate calculates should be no less than 40000 by mosapride peak, and symmetrical factor should be no less than 4.5.
In sample, single assorted content must not more than 0.2%.
2, dissolution determination method
Sample thief is appropriate, according to the dissolution method (paddle board method) in " Chinese Pharmacopoeia " 2010 editions two annex XC the 3rd methods, with phosphate buffer (pH6.8) 900mL for solvent, rotating speed is 50 turns per minute, operate in accordance with the law, through 45 minutes time, get solution and filter in right amount, discard at least 10mL just filtrate, collect subsequent filtrate; Precision measures subsequent filtrate 5ml, and with the dilution of 5ml dissolution medium as need testing solution.
Precision takes pre-through phosphorus pentoxide 60 DEG C of drying under reduced pressure mosapride citrate 28mg of 4 hours, puts in 100mL measuring bottle, adds mobile phase and dissolve and be diluted to scale, shake up, precision measures 2mL, puts in 200mL measuring bottle, add mobile phase and be diluted to scale, shake up, in contrast product solution.
According to drug release determination method (" Chinese Pharmacopoeia " version in 2010 two annex XD first methods), select ODS3C18 chromatographic column (Thermo, 15*4.6mm, 5 μm), with 0.03mol/L citric acid trisodium dihydrate solution (by dilute hydrochloric acid adjust ph to 3.3)-methanol-acetonitrile (24:9:7) for mobile phase, determined wavelength is 274nm, column temperature 40 DEG C, sample size 50 μ l, theoretical cam curve calculates should be not less than 4000 by mosapride peak, and tailing factor should be not more than 2.0.
3, the detection method of moisture and evaluation
Precision takes sample powder 0.2g, put in dry glass bottle, add absolute methanol 30mL, measure by dead-stop titration (Chinese Pharmacopoeia version in 2010 two annex VII A), and the result blank assay of titration is corrected (the blank volume consuming volumetric solution is B), be calculated as follows:
The weight W (g) of sample
Consume the volume A (mL) taking Xiu Shi liquid
F-every mL karl Fischer solution is equivalent to the mg amount of water
Content X (%)=(A-B) * F/W × 100% of water in sample
Measure 3 calculating mean values
4, medicine, reagent and instrument
Mosapride citrate (Chengdu limited company of Kang Hong Pharmaceutical collective); α lactose monohydrate (MEGGLE,
70); β Lactis Anhydrous (MEGGLE, DuraLac); Microcrystalline Cellulose PH103, PH102, PH101NF (Japanese Asahi Kasei Corporation); Cross-linked carboxymethyl cellulose sodium, polyvinylpolypyrrolidone, low-substituted hydroxypropyl cellulose, high replacement hyprolose, PVP K30, corn starch, hypromellose (Beijing Feng Lijingqiu commerce and trade Co., Ltd); Stearic acid, magnesium stearate, silicon dioxide (Anhui Shanhe Medicinal Subsidiary Material Co., Ltd.); Single punch tablet machine (the vertical science and technology of Beijing traditional Chinese medicines dragon, model DP30A), high performance liquid chromatograph (Shimadzu HL-2010A), digestion instrument (RC8MD dissolving-out tester is sent out in huge sky), vacuum drying oven (the upper grand experimental facilities company limited of Nereid, DZF-6050 type) comprehensive testing chamber for medicine stability (immortality experimental apparatus factory of Chongqing City, YSEI), karl Fischer Moisture Meter (Switzerland metrohm, 877Titrinoplus)
5, experiment content
5.1 mosapride citrate preparations Journal of Sex Research steady in a long-term
Pass through accelerated test, applicant has investigated existing lactinated mosapride citrate preparation long term storage rear stability change, result is as shown in table 1, wherein reference examples 1 obtains according to prescription in embodiment in CN104013591A 2 and preparation method, reference examples 2 obtains with reference to prescription in embodiment in ZL200510090146.0 8 and preparation method, all samples all adopts two alumiseal packaging, and carries out accelerated test under the condition of 60 DEG C/75%RH.
Detect mosapride citrate dissolution and relative substance content respectively at before Acceleration study after 1 month with accelerated test, concrete outcome is in table 1.
Table 1 mosapride citrate preparation Journal of Sex Research steady in a long-term
Before accelerated test, in sample, its related substances is extremely low, meets the requirement of internal control quality standard (single assorted content≤0.2%); After 1 month accelerated test, the mosapride citrate preparation dissolution of reference examples 1-2 had obvious decline before accelerated test, unknown impuritie A (relative retention time 12.1min) and unknown impuritie B (relative retention time 11.9min) is all there is in preparation, impurity content is compared with the increase had before accelerated test in various degree, single contaminant content higher than internal control quality standard (single assorted content≤0.2%), illustrates that above-mentioned mosapride citrate preparation long-time stability are all poor far away.
The 5.2 supplementary material compatibilitys are investigated
Dissimilar lactose is mixed homogeneously with mosapride citrate (API) by applicant, accelerated test 15 days under different humidity and temperature conditions, with the content of related substance for evaluation index investigates the supplementary material compatibility.By a large amount of the effects, applicant surprisingly finds that the existence of lactose and water has significant impact for the generation of mosapride citrate related substance and increase, and concrete outcome is in table 2,3.
Table 2 supplementary material compatibility experiments investigates result
Table 3 water plus lactose is on the impact of mosapride citrate stability
| Test example | Lactose kind | Acceleration environment | Result after accelerated test January |
| 1-3 | Lactose hydrous | Room temperature high humidity | Impurity content obviously increases, and sample segment list is mixed content overproof |
| 4-6 | Lactose hydrous | High-temperature closed | Impurity content obviously increases, and sample segment list is mixed content overproof |
| 7-9 | Lactis Anhydrous | Room temperature high humidity | Impurity content obviously increases, and sample segment list is mixed content overproof |
| 10-12 | Lactis Anhydrous | High-temperature closed | Impurity content is without significant change |
According to data in table 2,3, when lactose and mosapride citrate coexist, if containing water of crystallization in lactose, so no matter all there is at high humidity environment (test example 1-3) or in high-temperature closed state (test example 4-6) phenomenon that its related substances increases; If Lactis Anhydrous and mosapride citrate are placed in high humidity environment, its related substances can be caused equally obviously to increase (test example 7-9); But, when lactose and mosapride citrate coexist and at airtight anhydrous condition time (test example 10-12), even if variations in temperature, related substance is still without significant change.As can be seen here, when mosapride citrate and lactose and water (water of crystallization or free water) coexist, the content of related substance occurs significantly increasing phenomenon, illustrates that the existence of lactose and water is the key factor affecting mosapride citrate its related substances.
5.3 lactose and water are on the stable impact of pharmaceutical composition
Get mosapride citrate 5 parts, β Lactis Anhydrous 150 parts, low-substituted hydroxypropyl cellulose 12 parts, microcrystalline Cellulose PH10237 part, polyvinylpolypyrrolidone XL-104 part, micropowder silica gel 3 parts, stearic acid 2 parts, by the adjuvant vacuum drying in prescription, baking temperature is 60 DEG C, by controlling to control water content in adjuvant drying time.After drying, be about film-making under the environment of 45%RH at ambient humidity, concrete steps are: mosapride citrate, microcrystalline Cellulose PH105 and β Lactis Anhydrous are mixed, and crossing 50 mesh sieves dispersions once, is mixture one; Add in mixture one by crospovidone XL-10, low-substituted hydroxypropyl cellulose, micropowder silica gel, crossing 50 mesh sieve dispersions is once mixture two; Stearic acid is added in mixture two, always mix, discharging, tabletting, adopt two aluminum packaging, and detect finished product water content, dissolution and its related substances.Then, accelerated test 1 month under the condition of 60 DEG C/75%RH, detect sample dissolution and its related substances, result is as follows:
The content of table 4 lactose and water is to mosapride citrate stability influence
According to upper table data, higher with water quality ratio containing lactose in the pharmaceutical composition of mosapride citrate, medicine stability is better, when mass ratio >=54.2 of lactose and water, after accelerated test, pharmaceutical composition dissolution and single assorted content have no significant change, when lactose and water quality ratio are between 19.0-54.2, pharmaceutical composition after 1 month, though impurity content increases to some extent, but still meets internal control quality standard restriction (single assorted content≤0.2% through accelerated test; Test example 25 ~ 30).But, when lactose in pharmaceutical composition with water quality than < 19.0 time, after 1 month accelerates, mosapride citrate dissolution obviously reduces, and single assorted (impurity A or impurity B) content obviously rises in pharmaceutical composition, do not meet requirement (single assorted content≤0.2% of internal control quality standard; Test example 31 ~ 32).Visible, in the mosapride citrate pharmaceutical composition containing lactose, lactose and water quality ratio >=19.0, preferably >=54.2, most preferably >=60.0.
5.4 ambient humidities are on the impact of pharmaceutical composition stability
Get mosapride citrate 5 parts, β Lactis Anhydrous 75 parts, low-substituted hydroxypropyl cellulose 12 parts, microcrystalline Cellulose PH10237 part, polyvinylpolypyrrolidone XL-104 part, micropowder silica gel 3 parts, stearic acid 2 parts, adjuvant in prescription is carried out vacuum drying, baking temperature is 60 DEG C, drying time is 1 hour, parallel making 3 groups.Under ambient humidity is respectively 45%RH, 60%RH, 80%RH condition, carry out film-making after drying, concrete steps are: mosapride citrate, microcrystalline Cellulose PH105 and β Lactis Anhydrous are mixed, and crossing 50 mesh sieve dispersions once, is mixture one; Add in mixture one by crospovidone XL-10, low-substituted hydroxypropyl cellulose, micropowder silica gel, crossing 50 mesh sieve dispersions is once mixture two; Stearic acid is added in mixture two, always mix, discharging, tabletting, adopt two aluminum packaging, and detect finished product water content, dissolution and its related substances.Then, accelerated test 1 month under the condition of 60 DEG C/75%RH, detect sample dissolution and its related substances, result is as follows:
Table 5 ambient humidity is on the impact of mosapride citrate pharmaceutical composition stability
Above-mentioned result of study shows, adjuvant is after super-dry, if prepare in the environment of humidity higher (80%RH), then may because the reasons such as adjuvant moisture absorption cause water content in pharmaceutical composition higher, thus affect the long-time stability of preparation, cause dissolution to reduce, its related substances increases greatly, does not meet the requirement (single assorted content≤0.2%) of internal control quality standard.When ambient humidity is 60%RH, in the product prepared, water content is obviously lower, after accelerated test January, although its related substances raises to some extent, but still meets internal control index (single assorted content≤0.2%); When ambient humidity is 45%RH, in product, water content is only 1.5%, and after accelerated test January, its related substances is without significant change.Therefore, should select under the condition of ambient humidity≤60%RH, prepare pharmaceutical composition of the present invention, preferably prepare under ambient humidity≤40%RH condition.
Detailed description of the invention
Embodiment 1
Adjuvant in above-mentioned prescription is carried out vacuum drying, and baking temperature is 60 DEG C, and drying time is 1 hour, after drying under ambient humidity is 45%RH condition, mosapride citrate, microcrystalline Cellulose PH105 and β Lactis Anhydrous are mixed, crossing 50 mesh sieve dispersions once, is mixture one; Add in mixture one by crospovidone XL-10, low-substituted hydroxypropyl cellulose, micropowder silica gel, crossing 50 mesh sieve dispersions is once mixture two; Stearic acid is added in mixture two, always mix, discharging, tabletting, adopt two aluminum packaging, make 1000 altogether.Detect finished product dissolution and its related substances.The accelerated test of carrying out under the condition of then 60 DEG C/75%RH 1 month is investigated.Investigation result is as follows:
Table 6
Embodiment 2
Carry out vacuum drying to the adjuvant in prescription, baking temperature is 60 DEG C, and drying time is 1 hour, after drying under ambient humidity is 45%RH condition, mosapride citrate, microcrystalline Cellulose PH105 and β Lactis Anhydrous are mixed, crossing 50 mesh sieve dispersions once, is mixture one; Add in mixture one by crospovidone XL-10, low-substituted hydroxypropyl cellulose, micropowder silica gel, crossing 50 mesh sieve dispersions is once mixture two; Stearic acid is added in mixture two, always mix, discharging, tabletting, adopt two aluminum packaging, make 1000 altogether.Detect finished product dissolution and its related substances.The accelerated test of carrying out under the condition of then 60 DEG C/75%RH 1 month is investigated.Investigation result is as follows:
Table 7
Embodiment 3
Adjuvant in above-mentioned prescription is carried out vacuum drying, and baking temperature is 60 DEG C, and drying time is 1 hour, be under the condition of 45%RH at ambient humidity after drying, mosapride citrate, microcrystalline Cellulose PH105 and β Lactis Anhydrous are mixed, crossing 50 mesh sieve dispersions once, is mixture one; Add in mixture one by low-substituted hydroxypropyl cellulose, micropowder silica gel, crossing 50 mesh sieve dispersions is once mixture two; Mixture two is always mixed, discharging, subpackage, adopt aluminium plastic bag to pack, make 1000 bags altogether.Detect finished product dissolution and its related substances.The accelerated test of then carrying out under the condition of 60 DEG C/75%RH 1 month is investigated.Investigation result is as follows:
Table 8
Embodiment 4
Adjuvant in above-mentioned prescription is carried out vacuum drying, and baking temperature is 60 DEG C, and drying time is 25 minutes, be under the condition of 60%RH at ambient humidity after drying, mosapride citrate, microcrystalline Cellulose PH105 and β Lactis Anhydrous are mixed, crossing 50 mesh sieve dispersions once, is mixture one; Add in mixture one by low-substituted hydroxypropyl cellulose, micropowder silica gel, crossing 50 mesh sieve dispersions is once mixture two; Mixture two is always mixed, discharging, subpackage, adopt aluminium plastic bag to pack, make 1000 bags altogether.Detect finished product dissolution and its related substances.The accelerated test of then carrying out under the condition of 60 DEG C/75%RH 1 month is investigated.Investigation result is as follows:
Table 9
Embodiment 5
Adjuvant in above-mentioned prescription is carried out vacuum drying, and baking temperature is 60 DEG C, and drying time is 1 hour, after drying under ambient humidity is 60%RH condition, mosapride citrate, microcrystalline Cellulose PH102 and β Lactis Anhydrous are mixed, crossing 50 mesh sieve dispersions once, is mixture one; Add in mixture one by crospovidone XL-10, low-substituted hydroxypropyl cellulose, micropowder silica gel, crossing 50 mesh sieve dispersions is once mixture two; Stearic acid is added in mixture two, always mix, discharging, adopt plant capsule to fill, make 1000 altogether, adopt aluminium-plastic bubble plate packing.Detect finished product dissolution and its related substances.The accelerated test of carrying out under the condition of then 60 DEG C/75%RH 1 month is investigated.Investigation result is as follows:
Table 10
Embodiment 6
Adjuvant in above-mentioned prescription is carried out vacuum drying, and baking temperature is 60 DEG C, and drying time is 1 hour, after drying under ambient humidity is 52%RH condition, mosapride citrate, microcrystalline Cellulose PH102 and β Lactis Anhydrous are mixed, crossing 50 mesh sieve dispersions once, is mixture one; Add in mixture one by crospovidone XL-10, low-substituted hydroxypropyl cellulose, micropowder silica gel, crossing 50 mesh sieve dispersions is once mixture two; Glyceryl Behenate is added in mixture two, always mix, discharging, tabletting, adopt two aluminum packaging, make 1000 altogether.Detect finished product dissolution and its related substances.The accelerated test of carrying out under the condition of then 60 DEG C/75%RH 1 month is investigated.Investigation result is as follows:
Table 11
Embodiment 7
Carry out vacuum drying to the adjuvant in prescription, baking temperature is 60 DEG C, and drying time is 1 hour, after drying under ambient humidity is 35%RH condition, mosapride citrate, microcrystalline Cellulose PH105 and β Lactis Anhydrous are mixed, crossing 50 mesh sieve dispersions once, is mixture one; Add in mixture one by crospovidone XL-10, low-substituted hydroxypropyl cellulose, micropowder silica gel, crossing 50 mesh sieve dispersions is once mixture two; Stearic acid is added in mixture two, always mix, discharging, tabletting, adopt two aluminum packaging, make 1000 altogether.Detect finished product dissolution and its related substances.The accelerated test of carrying out under the condition of then 60 DEG C/75%RH 1 month is investigated.Investigation result is as follows:
Table 12
Embodiment 8
Adjuvant in above-mentioned prescription is carried out vacuum drying, and baking temperature is 60 DEG C, and drying time is 1 hour, after drying under ambient humidity is 55%RH condition, mosapride citrate, microcrystalline Cellulose PH105 and β Lactis Anhydrous are mixed, crossing 50 mesh sieve dispersions once, is mixture one; Add in mixture one by low-substituted hydroxypropyl cellulose, micropowder silica gel, crossing 50 mesh sieve dispersions is once mixture two; Mixture two is always mixed, discharging, subpackage, adopt aluminium plastic bag to pack, make 1000 bags altogether.Detect finished product dissolution and its related substances.The accelerated test of carrying out under the condition of then 60 DEG C/75%RH 1 month is investigated.Investigation result is as follows:
Table 13
Embodiment 9
Adjuvant in above-mentioned prescription is carried out vacuum drying, and baking temperature is 60 DEG C, and drying time is 1 hour, after drying under ambient humidity is 42%RH condition, mosapride citrate, microcrystalline Cellulose PH102 and β Lactis Anhydrous are mixed, crossing 50 mesh sieve dispersions once, is mixture one; Add in mixture one by crospovidone XL-10, low-substituted hydroxypropyl cellulose, micropowder silica gel, crossing 50 mesh sieve dispersions is once mixture two; Stearic acid is added in mixture two, always mix, discharging, carry out capsule-filling with plant capsule, adopt aluminium-plastic bubble plate packing, make 1000 altogether.Detect finished product dissolution and its related substances.The accelerated test of carrying out under the condition of then 60 DEG C/75%RH 1 month is investigated.Investigation result is as follows:
Table 14
Embodiment 10
Adjuvant in above-mentioned prescription is carried out vacuum drying, and baking temperature is 60 DEG C, and drying time is 60min, after drying under ambient humidity is 40%RH condition, mosapride citrate, microcrystalline Cellulose PH105 and β Lactis Anhydrous are mixed, crossing 50 mesh sieve dispersions once, is mixture one; Add in mixture one by crospovidone XL-10, low-substituted hydroxypropyl cellulose, micropowder silica gel, crossing 50 mesh sieve dispersions is once mixture two; Glyceryl monostearate is added in mixture two, always mix, discharging, tabletting, adopt two aluminum packaging, make 1000 altogether.Detect finished product dissolution and its related substances.The accelerated test of carrying out under the condition of then 60 DEG C/75%RH 1 month is investigated.Investigation result is as follows:
Table 15
Claims (9)
1. the pharmaceutical composition containing mosapride citrate, containing lactose and other pharmaceutically acceptable adjuvants in described pharmaceutical composition, is characterized in that: mass ratio >=19.0 of lactose and water in described pharmaceutical composition; Preferably >=54.2; More preferably >=60.0.
2. pharmaceutical composition according to claim 1, is characterized in that described lactose is Lactis Anhydrous.
3. pharmaceutical composition according to claim 1, is characterized in that: in described pharmaceutical composition, other pharmaceutically acceptable adjuvants are selected from one or more in disintegrating agent, lubricant, fluidizer.
4. pharmaceutical composition according to claim 3, it is characterized in that: described disintegrating agent be selected from microcrystalline Cellulose, cross-linked carboxymethyl cellulose sodium, polyvinylpolypyrrolidone, low-substituted hydroxypropyl cellulose, sodium carboxymethylcellulose pyce one or more, be preferably in low-substituted hydroxypropyl cellulose, microcrystalline Cellulose, polyvinylpolypyrrolidone one or more.
5. pharmaceutical composition according to claim 3, is characterized in that: described lubricant be selected from glyceryl palmitostearate, Glyceryl Behenate, glyceryl monostearate, stearic acid, magnesium stearate one or more.
6. pharmaceutical composition according to claim 3, is characterized in that: described fluidizer is one or more in Pulvis Talci, micropowder silica gel, is preferably micropowder silica gel.
7. the pharmaceutical composition according to any one of claim 1-6, is characterized in that: in described pharmaceutical composition, the mass percent of supplementary material is: mosapride citrate 1.42%-11.11%, lactose 44.12%-59.52%, disintegrating agent 31.11%-52.06%, lubricant 0.44%-1.69%, fluidizer 1.91%-2.73%.
8. pharmaceutical composition according to claim 7, is characterized in that: in described pharmaceutical composition, the mass percent of supplementary material is: mosapride citrate 3.36%, lactose 57.72%, disintegrating agent 35.57%, fluidizer 2.01%, lubricant 1.34%.
9. the preparation method of the pharmaceutical composition containing mosapride citrate according to any one of claim 1-8, concrete steps are: by lactose and other pharmaceutically acceptable adjuvant dryings, then under the condition of ambient humidity≤60%RH, mosapride citrate is even with lactose, disintegrating agent, fluidizer and mix lubricant successively, and tabletting, encapsulated or fill become powder; Preferably, described lactose and other pharmaceutically acceptable adjuvants vacuum drying 30-60min at 60 DEG C, described ambient humidity≤45%RH.
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN107661506A (en) * | 2016-07-26 | 2018-02-06 | 江苏豪森药业集团有限公司 | pharmaceutical preparation of mosapride citrate and preparation method thereof |
| CN107744509A (en) * | 2017-10-24 | 2018-03-02 | 浙江昂利康制药股份有限公司 | Mosapride Citrate Tablets agent and preparation method thereof |
| CN108324697A (en) * | 2017-01-19 | 2018-07-27 | 科贝源(北京)生物医药科技有限公司 | A kind of capsule and preparation method thereof containing mosapride citrate |
| CN109745293A (en) * | 2017-11-08 | 2019-05-14 | 成都康弘药业集团股份有限公司 | A kind of 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 |
| CN111514111A (en) * | 2020-05-07 | 2020-08-11 | 福建海西新药创制有限公司 | Pharmaceutical composition containing mosapride citrate and preparation method thereof |
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| CN1969857A (en) * | 2005-11-23 | 2007-05-30 | 上海秀新臣邦医药科技有限公司 | Mosapride citrate capsule and preparation process thereof |
| CN101273973A (en) * | 2007-03-28 | 2008-10-01 | 成都康弘科技实业（集团）有限公司 | Pharmaceutical combination containing Mosapride citrate and method of preparing the same |
| CN101816639A (en) * | 2010-01-15 | 2010-09-01 | 鲁南制药集团股份有限公司 | Tablets of mosapride citrate and preparation method thereof |
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN107661506A (en) * | 2016-07-26 | 2018-02-06 | 江苏豪森药业集团有限公司 | pharmaceutical preparation of mosapride citrate and preparation method thereof |
| 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 |
| CN108324697A (en) * | 2017-01-19 | 2018-07-27 | 科贝源(北京)生物医药科技有限公司 | A kind of capsule and preparation method thereof containing mosapride citrate |
| CN108324697B (en) * | 2017-01-19 | 2021-03-19 | 科贝源(北京)生物医药科技有限公司 | Mosapride citrate-containing capsule and preparation method thereof |
| CN107744509A (en) * | 2017-10-24 | 2018-03-02 | 浙江昂利康制药股份有限公司 | Mosapride Citrate Tablets agent and preparation method thereof |
| CN109745293A (en) * | 2017-11-08 | 2019-05-14 | 成都康弘药业集团股份有限公司 | A kind of pharmaceutical composition containing mosapride citrate |
| 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 |
| CN111514111A (en) * | 2020-05-07 | 2020-08-11 | 福建海西新药创制有限公司 | Pharmaceutical composition containing mosapride citrate and preparation method thereof |
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