CN112451511A - Metformin hydrochloride preparation and preparation method thereof - Google Patents
Metformin hydrochloride preparation and preparation method thereof Download PDFInfo
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Abstract
The invention provides a metformin hydrochloride preparation and its preparation method, the raw materials used, according to the weight percentage, include 40-80% sustained release pellet, 0-20% quick-release granule, 4-6% microcrystalline cellulose, 9-10% polyvidone K90F, 1-2% cross-linked polyvidone, 0.8-1.5% polyglycol 6000, adopt specially made sustained release pellet and quick-release granule of the invention, control the water content rationally, and mix with the square cone mixer, metformin hydrochloride preparation prepared finally can release the medicament rapidly after taking, control postprandial blood sugar to take effect fast, 60min of using medicine can reach 40% dissolution; the metformin hydrochloride preparation prepared by the invention has stable property, can be placed for a long time, and has a shelf life of 3 years.
Description
Technical Field
The invention belongs to the technical field of pharmaceutical preparations, and particularly relates to a metformin hydrochloride preparation and a preparation method thereof.
Background
Metformin hydrochloride is the first choice hypoglycemic agent for type 2 diabetes patients, belonging to first-line medication. The medicine has the functions of improving insulin resistance, reducing hepatic glucose production, inhibiting glucose absorption in intestinal tract, increasing insulin sensitivity, improving glucose utilization in peripheral tissue, and lowering fasting blood sugar and postprandial blood sugar.
Metformin hydrochloride is suitable for type 2 diabetes patients with unsatisfactory simple diet control, especially obesity and hyperinsulinemia patients, and has the effects of reducing blood sugar, and possibly reducing body weight and hyperinsulinemia. The absorption part of the metformin is mainly small intestine, the half-life period of absorption is 0.9-2.6 hours, the bioavailability is 50-60%, the metformin is orally taken for 0.58-2 hours, the plasma concentration reaches the peak value, and the metformin with higher level is accumulated in the wall of the gastrointestinal tract and is 10-100 times of the plasma concentration. The saliva content of kidney and liver is about 2 times of plasma concentration, the metformin structure is stable, the metformin structure is not combined with plasma protein, the metformin is discharged with urine in a prototype mode, the clearance is rapid, the half-life period of plasma is 1.7-4.5 hours, and 90% of serum is cleared within 12 hours.
The biguanide hypoglycemic agents on the market at present are mainly divided into two types, namely metformin hydrochloride tablets and metformin hydrochloride sustained-release tablets, and the biguanide tablets of the two types mainly have the following technical problems: 1. the common metformin hydrochloride tablet is difficult to reduce blood sugar for a long time, needs to be taken three times every day, has relatively large stimulation to stomach and intestinal tracts, and is easy to cause symptoms such as diarrhea and the like; 2. the metformin hydrochloride sustained release tablet has slow release speed, poor control effect on postprandial blood sugar and low absorption rate of metformin hydrochloride.
CN103976997B discloses a compound sustained-release capsule for reducing blood sugar and a preparation method thereof, which is obtained by respectively preparing a metformin hydrochloride combined sustained-release pellet and a saxagliptin quick-release pellet, and then filling the two pellets into a capsule according to a certain proportion, wherein the metformin hydrochloride combined sustained-release pellet is prepared by mixing the metformin hydrochloride quick-release pellet and the metformin hydrochloride sustained-release pellet according to a certain proportion, the metformin hydrochloride sustained-release pellet is prepared by coating a sustained-release coating film with the metformin hydrochloride quick-release pellet, the metformin hydrochloride quick-release pellet in the metformin hydrochloride combined sustained-release pellet accounts for 0-40%, and the metformin hydrochloride sustained-release pellet: 60 to 100 percent. However, in the patent, the metformin hydrochloride quick-release pellets are prepared by a powder lamination method, and the pellets prepared by the method have high water content and are not beneficial to long-term storage of the medicine; in addition, the metformin hydrochloride sustained-release pellet is prepared by coating the quick-release pellet, has larger particle size difference with the quick-release pellet, and is difficult to ensure uniform mixing and influence the drug effect because the quick-release pellet and the sustained-release pellet are easy to generate layering phenomenon due to smooth surface in the direct mixing process.
Disclosure of Invention
In order to solve the problems in the prior art and further optimize the prior art, the invention provides a metformin hydrochloride preparation and a preparation method thereof, so as to realize the following purposes:
1. the medicine is quickly released to reach the effective blood concentration;
2. the long-acting blood sugar reduction is kept;
3. prolonging shelf life of medicinal effect
In order to solve the technical problems, the invention adopts the following technical scheme:
the metformin hydrochloride preparation is characterized in that raw materials of the preparation are sustained-release pellets, quick-release granules, microcrystalline cellulose, povidone K90F, crospovidone and polyethylene glycol 6000;
the raw materials comprise, by weight: 60-80% of sustained-release pellets, 5-20% of quick-release granules, 4-6% of microcrystalline cellulose, 9-10% of povidone K90F, 1-2% of crospovidone, and 0.8-1.5% of polyethylene glycol 6000;
the sustained-release pellet comprises the raw materials of 35-40% of metformin hydrochloride, 9-10% of blank pellet core, 2-4% of povidone K90, 20-25% of Eudragit RS30D, 0.5-1% of triethyl citrate, 1-2% of anti-caking agent and 24-28% of purified water in percentage by weight;
the anti-sticking agent is one or more of talcum powder, glyceryl monostearate and polysorbate 80;
the particle size of the blank pellet core is 180-250 mu m;
the quick-release granules comprise 55-75% of metformin hydrochloride, 3-6% of povidone K30 and 20-40% of purified water in percentage by weight;
the preparation method of the metformin hydrochloride preparation is characterized by comprising the steps of preparation of sustained-release pellets, preparation of quick-release granules, total mixing and tabletting;
the preparation of the sustained-release pellet comprises the preparation of a drug layer base pill, and the drug layer base pill is dried until the LOD is 0-1.0%;
preparing the base pill with the medicine layer, wherein the air inlet temperature is 55-60 ℃, the air inlet amount is 78-80HZ, the spray gun atomization pressure is 0.15-0.2MPa, and the rotation speed of a peristaltic pump is controlled at 6-12 rpm;
preferably, the air inlet temperature is 60 ℃, the air inlet quantity is 80HZ, and the spray gun atomization pressure is 0.2 MPa;
the preparation of the sustained-release pellet comprises coating the sustained-release solution on the drug layer base pellet, wherein the air inlet temperature of the coating is 40-45 ℃, the air inlet amount is 66-70HZ, the spray gun atomization pressure is 0.18-0.2MPa, and the rotation speed of a peristaltic pump is controlled at 6-10 rpm;
preferably, the air inlet temperature is 45 ℃, the air inlet quantity is 70HZ, and the spray gun atomization pressure is 0.2 MPa;
the preparation of the quick-release granules comprises one-step granulation, wherein the one-step granulation is carried out, the air inlet temperature is 30-35 ℃, the air inlet quantity is 58-60HZ, the spray gun atomization pressure is 0.13-0.15MPa, and the rotating speed of a peristaltic pump is controlled at 6-15 rpm;
preferably, the air inlet temperature is 35 ℃, the air inlet amount is 60HZ, and the spray gun atomization pressure is 0.15 MPa;
the quick release particles are dried until the LOD is 1.0-1.5%;
the total mixing is carried out by adopting a square cone mixer, the rotating speed is 7-8rpm, and the mixing is carried out for 13-15 min;
and (3) tabletting, wherein the main pressure of the tabletting machine is 10-12KN, the pre-pressure is 2-5KN, the rotating speed of the feeder is 35rpm, and the rotating speed of the rotary table is 20 rpm.
By adopting the technical scheme, the invention has the beneficial effects that:
1. by adopting the preparation method of the metformin hydrochloride preparation, the prepared metformin hydrochloride preparation can quickly release the medicament after being taken, and the effect of controlling postprandial blood sugar is quick; the dissolution rate of 40 percent can be achieved after the drug is taken for 60min
2. By adopting the preparation method of the metformin hydrochloride preparation, the prepared metformin hydrochloride preparation has long time effect, can reduce blood sugar for a long time, and does not need to be taken for many times; in vitro dissolution data show that about 90 percent of the drug is released in 12 hours, and the long-acting release can be kept for 12 hours in vivo;
3. by adopting the preparation method of the metformin hydrochloride preparation, the prepared metformin hydrochloride preparation has stable property, can be placed for a long time, and has a shelf life of 3 years;
4. the metformin hydrochloride preparation prepared by the preparation method of the metformin hydrochloride preparation can reduce the stimulation to the gastrointestinal tract, and has high absorption rate and high bioavailability.
Description of the drawings: FIG. 1 is an in vitro dissolution curve at pH6.8
The specific implementation mode is as follows:
the invention is further illustrated below with reference to specific examples.
EXAMPLE 1 metformin hydrochloride preparation and method for producing the same
The preparation and the preparation method thereof comprise the following steps:
preparation of sustained-release pellets
1) Preparing an adhesive: weighing povidone K90 and purified water according to the prescription, and dissolving povidone K90 in the purified water until the mixture is clear and transparent for later use;
2) preparing a liquid medicine: weighing metformin hydrochloride raw material medicaments according to the prescription amount, dissolving the metformin hydrochloride raw material medicaments in the adhesive, and passing through a 80-mesh sieve before use;
3) medicine application: putting the blank pill cores in the prescription amount into a fluidized bed material chamber, setting the air inlet temperature at 60 ℃, the air inlet amount at 80HZ and the spray gun atomization pressure at 0.2MPa, controlling the rotating speed of a peristaltic pump at 6rpm, coating the liquid medicine on the blank pill cores, and drying the coated blank pill cores until the LOD is 0.6 percent to obtain medicine layer base pills;
the blank pill core has the particle size of 180 mu m;
the environmental temperature of the medicine application is controlled to be 20 ℃, and the relative humidity is controlled to be 45%;
4) preparing a slow-release solution: weighing each auxiliary material of the slow-release soluble layer according to the prescription amount, uniformly dispersing triethyl citrate into purified water, adding the water dispersion of the Uttqi RS30D, fully stirring, finally adding the talcum powder, uniformly stirring, and passing through a 80-mesh sieve before use;
5) coating: putting the prepared drug layer base pellet into a fluidized bed material chamber, setting air inlet temperature at 45 ℃, air inlet amount at 70HZ and spray gun atomization pressure at 0.2MPa, controlling the rotation speed of a peristaltic pump at 6rpm, coating the sustained-release solution on the drug layer pellet core, and drying after coating to obtain the sustained-release pellet;
preparation of quick-release granules
1) Preparing an adhesive: weighing povidone K30 and purified water according to the prescription, dissolving povidone K30 into the purified water until the purified water is clear and transparent, and passing through a 80-mesh sieve before use;
2) one-step granulation: weighing metformin hydrochloride raw material medicine according to the prescription amount, putting the metformin hydrochloride raw material medicine into a fluidized bed material chamber, setting the air inlet temperature to be 35 ℃, the air inlet amount to be 60HZ and the spray gun atomization pressure to be 0.15MPa, controlling the rotating speed of a peristaltic pump to be 15rpm to prepare quick-release particles, and drying the quick-release particles until the LOD of the quick-release particles is 1.0%;
three, total mixing
Weighing microcrystalline cellulose, povidone K90F, crospovidone and polyethylene glycol 6000 according to the formula amount, sequentially adding into a pyramid mixer, adding the prepared sustained-release pellets and quick-release granules, setting the rotation speed at 7rpm, mixing for 15min to obtain a total mixed material, and discharging;
fourthly, tabletting
Tabletting the total mixed material according to the theoretical tablet weight of 1.0 g/tablet, and tabletting by setting the main pressure of a tabletting machine at 10KN, the pre-pressure of 2KN, the rotating speed of a feeder of 35rpm and the rotating speed of a turntable of 20 rpm;
the amount of each raw material in example 1
Example 2A metformin hydrochloride preparation and a process for the preparation thereof
The preparation and the preparation method thereof comprise the following steps:
preparation of sustained-release pellets
1) Preparing an adhesive: weighing povidone K90 and purified water according to the prescription, and dissolving povidone K90 in the purified water until the mixture is clear and transparent for later use;
2) preparing a liquid medicine: weighing metformin hydrochloride raw material medicaments according to the prescription amount, dissolving the metformin hydrochloride raw material medicaments in an adhesive, and passing through a 80-mesh sieve before use;
3) medicine application: putting the blank pill cores in the prescription amount into a fluidized bed material chamber, setting the air inlet temperature at 60 ℃, the air inlet amount at 80HZ and the spray gun atomization pressure at 0.2MPa, controlling the rotating speed of a peristaltic pump at 8rpm, coating the liquid medicine on the blank pill cores, and drying the coated blank pill cores until the LOD is 0.8 percent to obtain medicine layer base pills;
the blank pill core has the particle size of 200 mu m;
the environmental temperature of the medicine application is controlled to be 2 ℃, and the relative humidity is 50%;
4) preparing a slow-release solution: weighing each auxiliary material of the slow-release soluble layer according to the prescription amount, uniformly dispersing triethyl citrate into purified water, adding the water dispersion of the Uttqi RS30D, fully stirring, finally adding the talcum powder, uniformly stirring, and passing through a 80-mesh sieve before use;
5) coating: putting the prepared drug layer base pellet into a fluidized bed material chamber, setting air inlet temperature at 45 ℃, air inlet amount at 70HZ and spray gun atomization pressure at 0.2MPa, controlling the rotation speed of a peristaltic pump at 8rpm, coating the sustained-release solution on the drug layer pellet core, and drying after coating to obtain the sustained-release pellet;
preparation of quick-release granules
1) Preparing an adhesive: weighing povidone K30 and purified water according to the prescription, dissolving povidone K30 into the purified water until the purified water is clear and transparent, and passing through a 80-mesh sieve before use;
2) one-step granulation: weighing metformin hydrochloride raw material medicine according to the prescription amount, putting the metformin hydrochloride raw material medicine into a fluidized bed material chamber, setting the air inlet temperature to be 35 ℃, the air inlet amount to be 60HZ and the spray gun atomization pressure to be 0.15MPa, controlling the rotating speed of a peristaltic pump to be 8rpm to prepare quick-release particles, and drying the quick-release particles until the LOD of the quick-release particles is 1.1;
three, total mixing
Weighing microcrystalline cellulose, povidone K90F, crospovidone and polyethylene glycol 6000 according to the formula amount, sequentially adding into a pyramid mixer, adding the prepared sustained-release pellets and quick-release granules, setting the rotation speed at 7rpm, mixing for 15min to obtain a total mixed material, and discharging;
fourthly, tabletting
Tabletting the total mixed material according to the theoretical tablet weight of 1.0 g/tablet, and tabletting by setting the main pressure of a tabletting machine at 10KN, the pre-pressure of 2KN, the rotating speed of a feeder of 35rpm and the rotating speed of a turntable of 20 rpm;
table for the amounts of raw materials used in example 2
Example 3A metformin hydrochloride preparation and a process for the preparation thereof
The preparation and the preparation method thereof comprise the following steps:
preparation of sustained-release pellets
1) Preparing an adhesive: weighing povidone K90 and purified water according to the prescription, and dissolving povidone K90 in the purified water until the mixture is clear and transparent for later use;
2) preparing a liquid medicine: weighing metformin hydrochloride raw material medicaments according to the prescription amount, dissolving the metformin hydrochloride raw material medicaments in an adhesive, and passing through a 80-mesh sieve before use;
3) medicine application: putting the blank pill cores in the prescription amount into a fluidized bed material chamber, setting the air inlet temperature at 60 ℃, the air inlet amount at 80HZ and the spray gun atomization pressure at 0.2MPa, controlling the rotating speed of a peristaltic pump at 12rpm, coating the liquid medicine on the blank pill cores, and drying the coated blank pill cores until the LOD is 0.8 percent to obtain medicine layer base pills;
the blank pill core has the particle size of 200 mu m;
the environmental temperature of the medicine application is controlled to be 22 ℃, and the relative humidity is 50%;
4) preparing a slow-release solution: weighing each auxiliary material of the slow-release soluble layer according to the prescription amount, uniformly dispersing triethyl citrate into purified water, adding the water dispersion of the Uttqi RS30D, fully stirring, finally adding the talcum powder, uniformly stirring, and passing through a 80-mesh sieve before use;
5) coating: putting the prepared drug layer base pellet into a fluidized bed material chamber, setting air inlet temperature at 45 ℃, air inlet amount at 70HZ and spray gun atomization pressure at 0.2MPa, controlling the rotation speed of a peristaltic pump at 10rpm, coating the sustained-release solution on the drug layer pellet core, and drying after coating to obtain the sustained-release pellet;
preparation of quick-release granules
1) Preparing an adhesive: weighing povidone K30 and purified water according to the prescription, dissolving povidone K30 into the purified water until the purified water is clear and transparent, and passing through a 80-mesh sieve before use;
2) one-step granulation: weighing metformin hydrochloride raw material medicine according to the prescription amount, putting the metformin hydrochloride raw material medicine into a fluidized bed material chamber, setting the air inlet temperature to be 35 ℃, the air inlet amount to be 60HZ and the spray gun atomization pressure to be 0.15MPa, controlling the rotating speed of a peristaltic pump to be 12rpm to prepare quick-release particles, and drying the quick-release particles until the LOD of the quick-release particles is 1.5%;
three, total mixing
Weighing microcrystalline cellulose, povidone K90F, crospovidone and polyethylene glycol 6000 according to the formula amount, sequentially adding into a pyramid mixer, adding the prepared sustained-release pellets and quick-release granules, setting the rotation speed at 7rpm, mixing for 15min to obtain a total mixed material, and discharging;
fourthly, tabletting
Tabletting the total mixed material according to the theoretical tablet weight of 1.0 g/tablet, and tabletting by setting the main pressure of a tabletting machine at 12KN, the pre-pressure of 2KN, the rotating speed of a feeder of 35rpm and the rotating speed of a turntable of 20 rpm;
table for the amounts of the raw materials in example 3
Example 4A metformin hydrochloride preparation and a process for the preparation thereof
The preparation and the preparation method thereof comprise the following steps:
preparation of sustained-release pellets
1) Preparing an adhesive: weighing povidone K90 and purified water according to the prescription, and dissolving povidone K90 in the purified water until the mixture is clear and transparent for later use;
2) preparing a liquid medicine: weighing metformin hydrochloride raw material medicine according to the prescription amount, and dissolving the metformin hydrochloride raw material medicine in an adhesive;
3) medicine application: putting the blank pill cores in the prescription amount into a fluidized bed material chamber, setting the air inlet temperature at 60 ℃, the air inlet amount at 80HZ and the spray gun atomization pressure at 0.2MPa, controlling the rotating speed of a peristaltic pump at 12rpm, coating the liquid medicine on the blank pill cores, and drying the coated blank pill cores until the LOD is 0.6 percent to obtain medicine layer base pills;
the blank pill core has the particle size of 250 mu m;
the environmental temperature of the medicine application is controlled to be 20 ℃, and the relative humidity is controlled to be 45%;
4) preparing a slow-release solution: weighing the auxiliary materials of the sustained-release layer according to the prescription amount, uniformly dispersing triethyl citrate into partial purified water, adding the water dispersion of the Uygur RS30D, and fully stirring; heating the rest purified water to 70 deg.C, adding glyceryl monostearate, stirring, homogenizing with homogenizer, mixing the above two parts, adding polysorbate 80, and stirring;
5) coating: putting the prepared drug layer base pellet into a fluidized bed material chamber, setting air inlet temperature at 45 ℃, air inlet amount at 70HZ and spray gun atomization pressure at 0.2MPa, controlling the rotation speed of a peristaltic pump at 10rpm, coating the sustained-release solution on the drug layer pellet core, and drying after coating to obtain the sustained-release pellet;
preparation of quick-release granules
1) Preparing an adhesive: weighing povidone K30 and purified water according to the prescription, dissolving povidone K30 into the purified water until the purified water is clear and transparent, and passing through a 80-mesh sieve before use;
2) one-step granulation: weighing metformin hydrochloride raw material medicine according to the prescription amount, putting the metformin hydrochloride raw material medicine into a fluidized bed material chamber, setting the air inlet temperature to be 35 ℃, the air inlet amount to be 60HZ and the spray gun atomization pressure to be 0.15MPa, controlling the rotating speed of a peristaltic pump to be 12rpm to prepare quick-release particles, and drying the quick-release particles until the LOD of the quick-release particles is 1.4%;
three, total mixing
Weighing microcrystalline cellulose, povidone K90F, crospovidone and polyethylene glycol 6000 according to the formula amount, sequentially adding into a pyramid mixer, adding the prepared sustained-release pellets and quick-release granules, setting the rotation speed at 7rpm, mixing for 15min to obtain a total mixed material, and discharging;
fourthly, tabletting
Tabletting the total mixed material according to the theoretical tablet weight of 1.0 g/tablet, and tabletting by setting the main pressure of a tabletting machine at 12KN, the pre-pressure of 5KN, the rotating speed of a feeder of 35rpm and the rotating speed of a turntable of 20 rpm;
example 4 dosage of each raw material
The dissolution and stability tests performed on the products of examples 1-4 of the invention gave the following results:
firstly, dissolution test:
the required instruments are as follows: electronic balance, dissolution instrument and ultraviolet-visible spectrophotometer
The method comprises the following steps: first method of release (sustained and controlled release formulation), second method of dissolution (paddle method)
Temperature: 37.0 deg.C
Rotating speed: 100 revolutions per minute
Detection wavelength: 233nm
Sampling time: 5min, 30min, 60min, 120min, 180min, 300min, 480min, 600min, 720 min.
Releasing medium: ph6.8 phosphate buffer: 6.805g of monopotassium phosphate and 0.896g of sodium hydroxide are taken, dissolved in water and diluted to 1000ml, and the pH value is adjusted to 6.8 +/-0.05 by using phosphoric acid or sodium hydroxide solution.
The dissolution rate and the dissolution curve of the product in a dissolution medium with pH6.8 are as follows:
and (4) conclusion:
the in vitro dissolution profile reflects: compared with a commercially available product (Glucophage XR), the product prepared in the embodiments 1,2,3 and 4 can reach a higher release degree in the first 60min, namely, after the patient takes the medicine, the metformin hydrochloride can quickly take effect to reach a higher level of blood concentration, so that the postprandial blood sugar can be quickly reduced; from 120min, the products prepared in the examples 1,2 and 3 have the dissolution curves basically consistent with those of the products sold on the market (Glucophage XR), and can control the blood sugar for a long time.
Second, stability test
Setting acceleration conditions (40 +/-2 ℃/75% RH +/-5% RH), detecting related substances of the self-made product and Glucophage XR in 0 month, 3 months and 6 months respectively, and obtaining the following results:
the results show that the products prepared by the embodiments 1,2,3 and 4 of the invention have less impurity increment after being placed for 6 months, the impurity content is not higher than that of the commercial products, and the product stability is higher.
Finally, it should be noted that: although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art will understand that various changes, modifications and substitutions can be made without departing from the spirit and scope of the present invention. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Claims (10)
1. The metformin hydrochloride preparation is characterized in that raw materials of the preparation are sustained-release pellets, quick-release granules, microcrystalline cellulose, povidone K90F, crospovidone and polyethylene glycol 6000.
2. The formulation according to claim 1, wherein the raw materials comprise, in weight percent: 60-80% of sustained-release pellets, 5-20% of quick-release granules, 4-6% of microcrystalline cellulose, 9-10% of povidone K90F, 1-2% of crospovidone and 0.8-1.5% of polyethylene glycol 6000.
3. The preparation of claim 1, wherein the sustained-release pellets comprise, in weight percent, 35-40% metformin hydrochloride, 9-10% empty pellet core, 2-4% povidone K90, 20-25% ewt RS30D, 0.5-1% triethyl citrate, 1-2% anti-adhesive agent, 24-28% purified water;
the antisticking agent is one or more of talcum powder, glyceryl monostearate and polysorbate 80.
4. The preparation of claim 1, wherein the quick-release granules comprise 55-75% by weight of metformin hydrochloride, 3-6% by weight of povidone K30, and 20-40% by weight of purified water.
5. The preparation method of the metformin hydrochloride preparation is characterized by comprising the steps of preparing sustained-release pellets, preparing quick-release granules and mixing; and the total mixing is carried out by adopting a square cone mixer at the rotating speed of 7-8 rpm.
6. The method for preparing the sustained-release pellets according to claim 5, wherein the preparation of the sustained-release pellets comprises preparing a drug layer-based pellet, and drying the drug layer-based pellet until the LOD is 0-1.0%.
7. The preparation method of claim 5, wherein the preparation of the sustained-release pellets comprises coating the sustained-release solution on the drug layer-based pellets, wherein the coating has an inlet air temperature of 40-45 ℃, an inlet air volume of 66-70Hz, a spray gun atomization pressure of 0.18-0.2MPa, and a peristaltic pump rotation speed of 6-10 rpm.
8. The process of claim 5, wherein the immediate release granules are dried to a LOD of 1.0 to 1.5%.
9. The preparation method of claim 5, wherein the preparation of the quick-release granules comprises one-step granulation, the one-step granulation comprises the steps of feeding air at 30-35 ℃, feeding air at 58-60HZ, spraying gun atomizing pressure at 0.13-0.15MPa, and controlling the rotation speed of a peristaltic pump at 6-15 rpm.
10. The process according to claim 5, further comprising tableting the tablets at a main compression pressure of 10-12KN and a pre-compression pressure of 2-5 KN.
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| CN104434846A (en) * | 2014-11-17 | 2015-03-25 | 中国药科大学 | Metformin hydrochloride enteric-coated sustained-release pellet and preparation method thereof |
| CN108451923A (en) * | 2018-05-31 | 2018-08-28 | 常州兰陵制药有限公司 | Metformin hydrochloride quick-release capsules and preparation method thereof |
| CN108938601A (en) * | 2018-08-15 | 2018-12-07 | 珠海润都制药股份有限公司 | A kind of metformin hydrochloride enteric-coated sustained release pellet and preparation method thereof |
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| WO2003066028A1 (en) * | 2002-02-01 | 2003-08-14 | Depomed, Inc. | Manufacture of oral dosage forms delivering both immediate-release and sustained-release drugs |
| WO2006099244A1 (en) * | 2005-03-11 | 2006-09-21 | Hong Kong Nitric Oxide Limited | Combination therapy for endothelial dysfunction, angina and diabetes |
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