CN1795846A - Peroral solid preparation of metformin hydrochloride and preparation method - Google Patents
Peroral solid preparation of metformin hydrochloride and preparation method Download PDFInfo
- Publication number
- CN1795846A CN1795846A CN 200410101492 CN200410101492A CN1795846A CN 1795846 A CN1795846 A CN 1795846A CN 200410101492 CN200410101492 CN 200410101492 CN 200410101492 A CN200410101492 A CN 200410101492A CN 1795846 A CN1795846 A CN 1795846A
- Authority
- CN
- China
- Prior art keywords
- oral solid
- solid formulation
- preparation
- metformin hydrochloride
- filler
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Landscapes
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
Abstract
An orally taken solid medicine for treating the insulin independent diabetics is prepared from meguan, disintegrant, filler, swelling additive, flowing aid, and other medicinal auxiliary or carrier.
Description
Technical field
The present invention relates to metformin hydrochloride oral solid preparation and preparation method thereof.
Background technology
Metformin hydrochloride is 1, and 1-dimethyl biguanide hydrochloride (1,1-Dimethylbiguanidehydrochloride) be the common drug that is used for the treatment of non-insulin-depending type (II type) diabetes.The common formulations of metformin hydrochloride administration is enteric coatel tablets, slow releasing tablet, the slow releasing capsule of conventional tablet and nearest report.
Taking of tablet and capsule exists following restriction and unfavorable factor:
-patient takes the aspect, and limited resource is difficult to swallow tablet and capsule for some patient;
-metformin hydrochloride is a water soluble drug, and medicine is too high at local concentration easily after its conventional tablet oral administration, thereby easily causes the digestive tract irritation.For the diabetes patient, need long-term prescription with controlling symptoms, so should reduce this stimulation as far as possible;
-for overcoming the digestive tract stimulation of conventional tablet, people have developed enteric coatel tablets and slow releasing tablet, slow releasing capsule, but enteric coatel tablets postpone drug effect; In addition, known postprandial hyperglycemia is one of characteristics of type ii diabetes, it also is the difficult point of glycemic control, therefore, the control postprandial hyperglycemia is to the glycemic control in the diabetics one day and stable significance arranged, though enteric coatel tablets and slow releasing tablet, slow releasing capsule can make blood drug level maintain one more stably level, overcome the local irritant effect of medicine, can not satisfy after the meal the clinical needs of glucose level control rapidly well.
Therefore, the pharmaceutical dosage form that still needs to develop new metformin hydrochloride satisfies all type ii diabetes people's medication demand.
Summary of the invention
The purpose of this invention is to provide the new pharmaceutical dosage form of metformin hydrochloride, be characterized in, thereby GI irritation effect, the taking medicine before meal that can alleviate conventional formulation can effectively be controlled level of postprandial blood sugar with rapid onset in the quickly disintegrated while.
Therefore, one aspect of the present invention relates to the metformin hydrochloride solid preparation, and described preparation comprises metformin hydrochloride and pharmaceutically acceptable disintegrating agent, filler, swellability adjuvant, fluidizer, and optional other pharmaceutic adjuvant or the carrier of containing.Said preparation has can rapid dispersive characteristics.
Another aspect of the present invention relates to the method for preparing above-mentioned oral solid formulation.It comprises that metformin hydrochloride is reached optional other pharmaceutic adjuvant or carrier with pharmaceutically acceptable disintegrating agent, filler, swellability adjuvant, fluidizer to be mixed, and is pressed into tablet.
According to the prescription of relevant dispersibility tablet under two appendix IA of Pharmacopoeia of the People's Republic of China version in 2000 tablet item, it must disintegrate in 3 minutes, and is uniformly dispersed.Therefore, the parameter that restriction can rapid dispersive tablet is as follows:
(1) in water disintegration rate fast and
(2) uniform particles is dispersed in the water of institute's disintegrate.
Disintegration rate and dispersing uniformity depend on used adjuvant, active component and employed preparation method.The present invention has taken into full account above-mentioned factor, in oral solid formulation of the present invention, except containing active component, also contains suitable disintegrating agent, filler, swellability adjuvant, fluidizer and optional other pharmaceutic adjuvant or carrier.
According to the present invention, the content of active ingredient hydrochloric acid metformin accounts for the 40-80% of oral solid formulation gross weight of the present invention, preferred 50-70%.The content of active ingredient hydrochloric acid metformin is 100mg-750mg in the unit dose oral solid formulation.
The disintegrating agent that is suitable as oral solid formulation of the present invention is the disintegrating agent that pharmaceutical field allows use, preferred swellbility is greater than the disintegrating agent of 5ml/g, it includes but not limited to carboxymethyl starch sodium (CMS-Na), the low hydroxypropyl cellulose (L-HPC) that replaces, crosslinked polyvinylpyrrolidone (PVPP), sodium carboxymethyl cellulose (CMC-Na), cross-linking sodium carboxymethyl cellulose (CCNa), starch and derivant thereof, also can select crospovidone (a kind of high polymer of N-vinyl-2-Pyrrolidone) and Kollidom-CI for use.
The content of disintegrating agent accounts for the 1.5-14% of oral solid formulation gross weight, preferred 2-12%.
The filler that is adopted in the oral solid formulation of the present invention can be used for increasing the weight and volume of tablet, be beneficial to molding and divided dose, it includes but not limited to water-insoluble filleies such as water-soluble fillers such as lactose, mannitol, sorbitol and microcrystalline Cellulose, calcium sulfate, calcium hydrogen phosphate.Wherein the flowability of microcrystalline Cellulose and compressibility are very suitable for direct powder compression, and microcrystalline Cellulose also can be used as binding agent, make tablet have suitable hardness, have the imbibition ability again and can shorten disintegration time.The microcrystalline cellulose of selling on the market have variety classes, comprise AvicelPH101 (50 microns of particle mean sizes) and Avicel PH102 (90 microns of particle mean sizes), though the two ability that helps directly compacting is close, but because thereby latter's granularity is given the mobile big of mixture greatly, so Avicel PH102 helps the direct compacting of fine powder mixture, therefore, the present invention preferably adopts Avicel PH102 as filler.
Described filler shared part by weight in oral solid formulation of the present invention is 10-25%, preferred 23%.
The swellability adjuvant that is adopted in the oral solid formulation of the present invention includes but not limited to guar gum, Herba Xanthii glue, alginate, polysaccharide, pregelatinized starch (amylum pregelatinisatum), hydrophilic cellulose class (as carboxymethylcellulose calcium (CMC-Ca), hydroxypropyl cellulose or hydroxypropyl emthylcellulose) etc.Wherein pregelatinized starch is quickly disintegrated modified starch, has the effect of disintegrating agent, binding agent and suspensoid.Because the good fluidity of pregelatinized starch has self-lubricity, the preparation that contains pregelatinized starch can no longer add lubricant.
Described swellability adjuvant shared weight ratio in oral solid formulation of the present invention is 6-20%.
" fluidizer " that is adopted in the oral solid formulation of the present invention is that those can stop granule to adhere, improve effectively the excipient of granule or powder flowbility.Because of micropowder silica gel has bigger specific surface area, be the mobile good regulator of powder, therefore can be used as the suitable fluidizer of preparation of the present invention.Simultaneously, its polarity is strong and hydrophilic is high, goes into tablet so help moisture penetration, can quicken the disintegrate of tablet.
Described fluidizer shared part by weight in oral solid formulation of the present invention is 1.0-8.8%, preferred 1.5%.
The sweeting agent or the correctives that are adopted in the oral solid formulation of the present invention comprise artificial or natural sweeting agent or correctives, as mannitol, sorbitol, saccharin sodium, aspartame, menthol, ammonium glyciricinate, and chocolate flavoring, lemon flavouring, mandarin orange flavor, Cortex cocois radicis spice, Fructus Pruni spice, pears spice etc.
The lubricant that is adopted in the oral solid formulation of the present invention includes but not limited to stearic acid, magnesium stearate, micropowder silica gel, Pulvis Talci, Stepanol MG, pregelatinized starch, stearyl fumarate etc.
Wetting agent that is adopted in the oral solid formulation of the present invention or binding agent include but not limited to water, ethanol, methylcellulose, polyvinylpyrrolidone (PVP), microcrystalline Cellulose, pregelatinized starch etc.
Can be through the mixture of the metformin hydrochloride of the present invention of mix homogeneously and above-mentioned adjuvant or carrier by standard method, for example adopt common rotary or centering type tablet machine to carry out tabletting and make tablet with polymolecularity.
Metformin hydrochloride oral solid preparation outward appearance provided by the invention is even, has enough mechanical strengths, can stand to preserve with transportation in possible infringement (being that friability is qualified,＜1%).Active component is evenly distributed therein, and the disintegration rate in water is very fast and dispersed homogeneous degree is qualified, and the method test through the pharmacopeia regulation complies with relevant regulations.
Compare with existing metformin hydrochloride preparation, the oral solid formulation of metformin hydrochloride of the present invention has the following advantages: be suitable for treatment and swallow the inconvenient patient of solid preparation; Because oral solid formulation of the present invention is disintegrate and rapidly dispersion fast, make the medicine homodisperse, the digestive tract local drug concentration is unlikely to too high, thereby has avoided the stimulation that causes because of local drug concentration is too high; Metformin hydrochloride oral solid preparation of the present invention disintegrate and dispersion rapidly, the rapid onset of taking medicine before meal can be controlled level of postprandial blood sugar effectively.
The specific embodiment
The following example is used for illustrating the present invention, and it is not regarded as limiting of the invention.
Embodiment 1. contains oral solid formulation 1 of 250mg metformin hydrochloride and preparation method thereof
The oral solid formulation 1 of unit dose composed as follows:
| Component | Weight (mg) | Percentage composition (%) |
| The micropowder silica gel of metformin hydrochloride carboxymethyl starch sodium microcrystalline Cellulose AVICEL PH102 pregelatinized starch | 250 12 68 68 2 | 62.5 3 17 17 0.5 |
Preparation method: earlier metformin hydrochloride is pulverized, crossed 80 mesh standard sieves, other adjuvant is also crossed 80 mesh standard sieves respectively; The all raw materials of weighing are pressed equivalent incremental method ground and mixed then respectively, and order by merging is: metformin hydrochloride elder generation and micropowder silica gel ground and mixed, follow and the pregelatinized starch ground and mixed, and mix with microcrystalline Cellulose then, add carboxymethyl starch sodium at last.The mixture that obtains obtains runny powder with 40 mesh sieve mix homogeneously.With described direct powder compression.The humidity that should control environment in the operating process is below 60%.
Embodiment 2. contains oral solid formulation 2 of 250mg metformin hydrochloride and preparation method thereof
The oral solid formulation 2 of unit dose composed as follows:
| Component | Weight (mg) | Percentage composition (%) |
| The micropowder silica gel of metformin hydrochloride crospolyvinylpyrrolidone microcrystalline Cellulose AVICEL PH102 pregelatinized starch | 250 16 92 36 6 | 62.5 4 23 9 1.5 |
According to the preparation method of embodiment 1, just change disintegrating agent into crospolyvinylpyrrolidone.The powder flowbility of the mixture that obtains is satisfactory, and compacting also has no difficulty.
Embodiment 3. contains oral solid formulation 3 of 250mg metformin hydrochloride and preparation method thereof
The oral solid formulation 3 of unit dose composed as follows:
| Component | Weight (mg) | Percentage composition (%) |
| Metformin hydrochloride crospovidone microcrystalline cellulose AVICEL PH102 dolomol starch superfine silica gel powder polyvinylpyrrolidone | 250 56 24 2 68 2 | 62.5 13.5 6 0.5 17 0.5 is an amount of |
Preparation method: earlier metformin hydrochloride is pulverized, crossed 80 mesh standard sieves, other adjuvant is also crossed 80 mesh standard sieves respectively.Then, crospovidone mix homogeneously with metformin hydrochloride, micropowder silica gel, starch, microcrystalline Cellulose, 2/3 amount, polyvinylpyrrolidone aqueous solution with 10% is done binding agent, the preparation soft material is crossed 30 mesh sieves and is granulated, and drying is about 2 hours under 70 ℃ of conditions, 26 mesh standard sieve granulate, the crospovidone and the magnesium stearate that add remaining 1/3 amount, and mix homogeneously, tabletting.
Embodiment 4. contains oral solid formulation 4 of 250mg metformin hydrochloride and preparation method thereof
The oral solid formulation 4 of unit dose composed as follows:
| Component | Weight (mg) | Percentage composition (%) |
| Metformin hydrochloride low-substituted hydroxypropyl cellulose microcrystalline Cellulose AVICEL PH102 starch micropowder silica gel magnesium stearate | 250 24 44 56 26 2 | 62.5 6 11 14 5.5 1 |
Low-substituted hydroxypropyl cellulose, microcrystalline Cellulose, starch, micropowder silica gel mix homogeneously with metformin hydrochloride, 2/3 amount, be pressed into the suitable thin slice of hardness with rolling process, pulverize again, cross 20 orders～30 mesh sieves, with the granule that obtains and remaining low-substituted hydroxypropyl cellulose, magnesium stearate mix homogeneously, tabletting.
Embodiment 5. contains oral solid formulation 5 of 250mg metformin hydrochloride and preparation method thereof
The oral solid formulation 5 of unit dose composed as follows:
| Component | Weight (mg) | Percentage composition (%) |
| The micropowder silica gel of metformin hydrochloride cross-linking sodium carboxymethyl cellulose microcrystalline Cellulose AVICEL PH102 pregelatinized starch | 250 16 68 4 26 | 62.5 4 17 10 6.5 |
According to the preparation method of embodiment 1, just change disintegrating agent into cross-linking sodium carboxymethyl cellulose.The powder flowbility of the mixture that obtains is satisfactory, and compacting also has no difficulty.
The disintegrate qualification testing of embodiment 6. oral solid formulations of the present invention
According to " two described methods of Pharmacopoeia of People's Republic of China version in 2000, the tablet that embodiment 2 is obtained carries out the disintegrate experiment.
Get 2 in tablet, place the jolting of 100ml water, described tablet is in 19 ℃～21 ℃ water, and all disintegrate is also by No. 2 sieves in 3 minutes, and it meets the pharmacopeia pertinent regulations.
The dissolution test of embodiment 7. oral solid formulations of the present invention
With water is dissolution medium, and tablet that embodiment 2 is obtained and commercially available ordinary tablet (available from Shanghai Xinyi Pharmaceutical Co., Ltd, wherein every hydrochloric metformin 250mg) carry out the dissolution comparative experiments.
The sampling time point of oral solid formulation of the present invention is decided to be respectively: 20 seconds, 40 seconds, 60 seconds, 80 seconds, 100 seconds, 120 seconds.
The sampling time point of commercially available ordinary tablet is decided to be respectively: 2 minutes, 4 minutes, 6 minutes, 8 minutes, 10 minutes, 12 minutes.
According to 2000 editions described methods of " pharmacopeia " P539-540, precision weighed and 6 in sample that tablet weight variation is qualified respectively according to dissolution method (appendix X C first method), with 1000ml water is solvent, rotating speed is that per minute 100 changes, operation in accordance with the law, through the stipulated time, get solution 10ml and filter, and replenish corresponding dissolution medium.Precision is measured filtrate 2ml and is placed the 100ml measuring bottle, is diluted with water to scale, with spectrophotography (appendix IV A), measures trap at the wavelength place of 233nm.Make five parallel sample on every each time point of sample, average, and calculate dissolution.
The result sees Table 1-4 respectively.
The trap value of table 1. metformin hydrochloride oral solid preparation of the present invention
| The tablet numbering | Time | Preparation trap of the present invention | The trap meansigma methods | ||||
| The 1st | 20 seconds 40 seconds 60 seconds 80 seconds 100 seconds 120 seconds | 0.1814 0.2952 0.3534 0.3798 0.3872 0.3855 | 0.1804 0.2948 0.3533 0.3796 0.3875 0.3855 | 0.1805 0.2948 0.3531 0.3796 0.3875 0.3852 | 0.1805 0.2949 0.3535 0.3794 0.3874 0.3856 | 0.1804 0.295 0.3538 0.3794 0.3875 0.3855 | 0.1806 0.2949 0.3534 0.3796 0.3874 0.3855 |
| The 2nd | 20 seconds 40 seconds 60 seconds 80 seconds 100 seconds 120 seconds | 0.1991 0.3123 0.3679 0.3882 0.3911 0.3874 | 0.1982 0.3125 0.3684 0.3875 0.3912 0.3871 | 0.1985 0.3124 0.3685 0.3869 0.3912 0.3869 | 0.1982 0.3125 0.3686 0.3867 0.3914 0.3872 | 0.1982 0.312 0.3685 0.3869 0.3914 0.3873 | 0.1984 0.3123 0.3684 0.3872 0.3913 0.3872 |
| The 3rd | 20 seconds 40 seconds 60 seconds 80 seconds 100 seconds 120 seconds | 0.2035 0.3171 0.3819 0.4009 0.4023 0.3948 | 0.203 0.317 0.3821 0.4013 0.4025 0.3949 | 0.2032 0.3158 0.382 0.4013 0.4032 0.3947 | 0.2032 0.3168 0.382 0.401 0.4034 0.3949 | 0.203 0.3165 0.3816 0.4005 0.4034 0.3949 | 0.2032 0.3168 0.3819 0.4010 0.4030 0.3948 |
| The 4th | 20 seconds 40 seconds 60 seconds 80 seconds 100 seconds 120 seconds | 0.1388 0.2666 0.3365 0.3728 0.3868 0.3894 | 0.1385 0.2666 0.3363 0.3727 0.3866 0.3893 | 0.1386 0.2666 0.3362 0.3728 0.3869 0.3893 | 0.1386 0.2666 0.3362 0.3731 0.3868 0.3892 | 0.1386 0.2668 0.3362 0.3722 0.3868 0.3893 | 0.1386 0.2666 0.3363 0.3727 0.3868 0.3893 |
| The 5th | 20 seconds 40 seconds 60 seconds 80 seconds 100 seconds 120 seconds | 0.1339 0.2675 0.3388 0.3769 0.3883 0.3881 | 0.134 0.2676 0.3388 0.3769 0.3882 0.3881 | 0.1339 0.2674 0.3384 0.3769 0.3883 0.3877 | 0.134 0.2673 0.3382 0.3768 0.3882 0.3877 | 0.134 0.2675 0.3382 0.3765 0.3883 0.3879 | 0.1340 0.2675 0.3385 0.3768 0.3883 0.3879 |
| The 6th | 20 seconds 40 seconds 60 seconds 80 seconds 100 seconds 120 seconds | 0.1873 0.3008 0.3617 0.3862 0.391 0.3885 | 0.1875 0.3011 0.3618 0.3864 0.3913 0.3882 | 0.1876 0.3007 0.3615 0.3867 0.3914 0.3883 | 0.1878 0.3005 0.3615 0.3862 0.3914 0.3881 | 0.1876 0.3008 0.3618 0.3863 0.3916 0.3884 | 0.1876 0.3008 0.3617 0.3864 0.3913 0.3883 |
The dissolution of table 2. metformin hydrochloride oral solid preparation of the present invention:
| The tablet numbering | Time (second) | |||||
| 20 | 40 | 60 | 80 | 100 | 120 | |
| 123456 average SD | 45.27 49.73 50.92 34.74 33.57 47.01 43.54 7.54 | 73.92 78.28 79.41 66.83 67.03 75.38 73.48 5.44 | 88.58 92.33 95.72 84.28 84.83 90.64 89.40 4.42 | 95.13 97.05 100.50 93.41 94.44 96.83 96.23 2.52 | 97.10 98.06 100.99 96.94 97.31 98.08 98.08 1.51 | 96.61 97.04 98.96 97.57 97.22 97.32 97.45 0.80 |
The trap value of the commercially available conventional tablet of table 3. metformin hydrochloride
| The tablet numbering | Time | Commercially available ordinary tablet trap | The trap meansigma methods | ||||
| The 1st | 2 minutes 4 minutes 6 minutes 8 minutes 10 minutes 12 minutes | 0.1134 0.2287 0.3112 0.3646 0.397 0.4009 | 0.1135 0.2286 0.3109 0.3643 0.3972 0.4008 | 0.1137 0.2284 0.3111 0.3643 0.397 0.4006 | 0.1134 0.2286 0.3111 0.3643 0.3967 0.4006 | 0.1134 0.2284 0.3111 0.3646 0.3966 0.4011 | 0.1135 0.2285 0.3111 0.3644 0.3969 0.4008 |
| The 2nd | 2 minutes 4 minutes 6 minutes 8 minutes 10 minutes 12 minutes | 0.0922 0.1850 0.2686 0.3303 0.3742 0.4066 | 0.0924 0.1851 0.2684 0.3303 0.3742 0.4065 | 0.0924 0.1851 0.2686 0.3303 0.3744 0.4063 | 0.0922 0.1854 0.2683 0.3303 0.3739 0.4065 | 0.0923 0.1851 0.2685 0.3302 0.3739 0.4066 | 0.0923 0.1851 0.2685 0.3303 0.3741 0.4065 |
| The 3rd | 2 minutes 4 minutes 6 minutes 8 minutes 10 minutes 12 minutes | 0.1131 0.2181 0.3031 0.3636 0.3973 0.4083 | 0.1132 0.2186 0.3031 0.3632 0.3976 0.4079 | 0.1133 0.2185 0.3032 0.3631 0.3977 0.4074 | 0.1131 0.2185 0.3029 0.3632 0.3973 0.4074 | 0.1131 0.2183 0.3032 0.3632 0.3977 0.4075 | 0.1132 0.2184 0.3031 0.3633 0.3975 0.4077 |
| The 4th | 2 minutes 4 minutes 6 minutes 8 minutes 10 minutes 12 minutes | 0.0676 0.1445 0.2108 0.2642 0.3080 0.3432 | 0.068 0.1447 0.2107 0.2642 0.308 0.3432 | 0.0674 0.1446 0.2108 0.264 0.3079 0.3429 | 0.0681 0.1447 0.2107 0.2642 0.3079 0.343 | 0.0678 0.1447 0.2105 0.2641 0.3078 0.3429 | 0.0678 0.1446 0.2107 0.2641 0.3079 0.3430 |
| The 5th | 2 minutes 4 minutes 6 minutes 8 minutes 10 minutes 12 minutes | 0.097 0.1966 0.2764 0.3404 0.3806 0.4088 | 0.0962 0.1968 0.2763 0.3404 0.3806 0.4089 | 0.0962 0.1977 0.2766 0.3402 0.3804 0.4086 | 0.0962 0.1982 0.2765 0.3405 0.3804 0.4085 | 0.0959 0.1983 0.2763 0.3404 0.3802 0.4085 | 0.0963 0.1975 0.2764 0.3404 0.3804 0.4087 |
| The 6th | 2 minutes 4 minutes 6 minutes 8 minutes 10 minutes 12 minutes | 0.1115 0.2123 0.2967 0.3566 0.3929 0.399 | 0.1114 0.2124 0.2969 0.3566 0.3928 0.3991 | 0.1114 0.2121 0.2973 0.3563 0.3926 0.399 | 0.1115 0.2123 0.297 0.3566 0.3927 0.3988 | 0.1114 0.2124 0.2968 0.3564 0.3928 0.3988 | 0.1114 0.2123 0.2969 0.3565 0.3928 0.3989 |
The dissolution of the commercially available conventional tablet of table 4. metformin hydrochloride:
| The tablet numbering | Time (minute) | |||||
| 2 | 4 | 6 | 8 | 10 | 12 | |
| 123456 average SD | 28.44 23.13 28.36 16.99 24.14 27.93 24.83 4.47 | 57.28 46.40 54.74 36.25 49.50 53.21 49.56 7.57 | 77.96 67.29 75.96 52.81 69.28 74.42 69.62 9.18 | 91.33 82.78 91.04 66.20 85.31 89.35 84.34 9.50 | 99.47 93.76 99.63 77.17 95.35 98.44 93.97 8.56 | 100.45 101.88 102.18 85.97 102.42 99.98 98.82 6.37 |
Above data substitution Weibull function is obtained the stripping parameter: the time T 50 of the time T d of stripping 63.2%, stripping 50% and form parameter m.The result is as follows:
Metformin hydrochloride oral solid preparation of the present invention: Td-28.8 second, T50-22.8 second, m=0.77;
Metformin hydrochloride conventional tablet: Td-4.91 minute, T50=3.87, minute m=1.42.
As seen, obviously the commercially available conventional tablet than metformin hydrochloride is rapid in the stripping of hydrochloric acid dimethylguanidine oral solid formulation of the present invention.
Claims (10)
1, metformin hydrochloride oral solid preparation, wherein comprise as the metformin hydrochloride of active component and pharmaceutically acceptable disintegrating agent, filler, swellability adjuvant, fluidizer, and optional contain other pharmaceutic adjuvant or carrier, and the active ingredient hydrochloric acid metformin accounts for the 40-80% of oral solid formulation gross weight.
2, the described oral solid formulation of claim 1, wherein contained active ingredient hydrochloric acid metformin is 100mg-750mg in the unit dose.
3, claim 1 or 2 described oral solid formulations, wherein said disintegrating agent is selected from one or more in the following material: carboxymethyl starch sodium, low-substituted hydroxypropyl cellulose, crosslinked polyvinylpyrrolidone, sodium carboxymethyl cellulose, cross-linking sodium carboxymethyl cellulose, crospovidone, starch and derivant thereof.
4, claim 1 or 2 described oral solid formulations, wherein said filler is selected from one or more in the following material: water-insoluble filler such as water-soluble filler such as lactose, mannitol, sorbitol, xylitol, lactose and microcrystalline Cellulose, calcium sulfate, calcium hydrogen phosphate, calcium carbonate, calcium bicarbonate, calcium phosphate.
5, claim 1 or 2 described oral solid formulations, wherein said swellability adjuvant is selected from one or more in the following material: guar gum, Herba Xanthii glue, alginate, polysaccharide, pregelatinized starch, hydrophilic cellulose class.
6, claim 1 or 2 described oral solid formulations, wherein said fluidizer is micropowder silica gel.
7, claim 1 or 2 oral solid formulation, wherein said disintegrating agent accounts for the 1.5-14% of oral solid formulation gross weight.
8, claim 1 or 2 oral solid formulation, wherein said filler accounts for the 10-25% of oral solid formulation gross weight.
9, claim 1 or 2 oral solid formulation, wherein said swellability adjuvant accounts for the 6-20% of oral solid formulation gross weight.
10, the method for the metformin hydrochloride oral solid preparation of preparation claim 1-10 described in each, it comprises that the hydrochloric acid diformazan is reached optional other pharmaceutic adjuvant or carrier with guanidine with pharmaceutically acceptable disintegrating agent, filler, swellability adjuvant, cosolvent to be mixed, and is pressed into tablet.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410101492 CN1795846A (en) | 2004-12-21 | 2004-12-21 | Peroral solid preparation of metformin hydrochloride and preparation method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410101492 CN1795846A (en) | 2004-12-21 | 2004-12-21 | Peroral solid preparation of metformin hydrochloride and preparation method |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1795846A true CN1795846A (en) | 2006-07-05 |
Family
ID=36817301
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200410101492 Pending CN1795846A (en) | 2004-12-21 | 2004-12-21 | Peroral solid preparation of metformin hydrochloride and preparation method |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1795846A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109044988A (en) * | 2018-09-29 | 2018-12-21 | 哈尔滨珍宝制药有限公司 | A kind of metformin hydrochloride medicinal composition and its preparation method and application |
| CN111939135A (en) * | 2020-09-02 | 2020-11-17 | 苏州东瑞制药有限公司 | Sustained-release tablet of metformin hydrochloride medicament and preparation method thereof |
-
2004
- 2004-12-21 CN CN 200410101492 patent/CN1795846A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109044988A (en) * | 2018-09-29 | 2018-12-21 | 哈尔滨珍宝制药有限公司 | A kind of metformin hydrochloride medicinal composition and its preparation method and application |
| CN109044988B (en) * | 2018-09-29 | 2021-03-23 | 哈尔滨珍宝制药有限公司 | Metformin hydrochloride pharmaceutical composition and preparation method and application thereof |
| CN111939135A (en) * | 2020-09-02 | 2020-11-17 | 苏州东瑞制药有限公司 | Sustained-release tablet of metformin hydrochloride medicament and preparation method thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN1101187C (en) | Fluoxetine pahrmaceutical formulations | |
| CN1248690C (en) | Oral preparation containing ranolazine hydrochloride for treating cardiovascular disease | |
| CN1240374C (en) | Rapidly disintegrating methylcellulose tablets | |
| CN1180782C (en) | Phosphate-binding polymer preparations | |
| CN100335046C (en) | Composition | |
| CN1339972A (en) | Tablets quickly disintegrated in the oral cavity | |
| CN1276719A (en) | Rapidly disintegrating methylcellulose tablets | |
| CN1181237A (en) | Solid pharmaceutical preparation | |
| CN1805738A (en) | Extended-release tablets of metformin | |
| CN1248681C (en) | Solid orally-dispersible pharmaceutical formulation | |
| CN101167731A (en) | Dispersible tablet containing metformin and glibenclamide and preparation method thereof | |
| CN1738600A (en) | Pharmaceutical compositions and dosage forms for buccal and sublingual delivery of tizanidine and methods of administering tizanidine sublingually or buccally | |
| CN107669645A (en) | The preparation method of ciprofloxacin hydrocloride tablets | |
| CN1795846A (en) | Peroral solid preparation of metformin hydrochloride and preparation method | |
| CN1806805A (en) | Leponex orally disintegrating tablet and preparation method thereof | |
| CN1586483A (en) | Oral disintegration tablet of silaenafil and its pharmaceutically receptible salt and its preparing method | |
| CN1247195C (en) | Silibinin oral disintegration tablet and its preparing method | |
| CN1323667C (en) | Notoginseng dispersible tablet and its preparing process | |
| CN1582927A (en) | Oral disintegrants of nimodipine and their preparation | |
| CN1254240C (en) | Silibinin meglumine salt oral disintegration tablet preparation and its preparing method | |
| CN106727375B (en) | Agomelatine tablet and preparation method thereof | |
| CN1895250A (en) | Gliquilone slow-releasing preparation | |
| CN106551927A (en) | Pharmaceutical composition comprising vildagliptin and metformin hydrochloride and preparation method thereof | |
| CN114191403B (en) | Kurarinone tablet and preparation method thereof | |
| CN1297263C (en) | Calcium gluconate oral disintegrating tablet and its preparation process |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |