CN101536989A - Metformin hydrochloride intragastric floating sustained-release tablet and preparation method thereof - Google Patents
Metformin hydrochloride intragastric floating sustained-release tablet and preparation method thereof Download PDFInfo
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- CN101536989A CN101536989A CN200810019838A CN200810019838A CN101536989A CN 101536989 A CN101536989 A CN 101536989A CN 200810019838 A CN200810019838 A CN 200810019838A CN 200810019838 A CN200810019838 A CN 200810019838A CN 101536989 A CN101536989 A CN 101536989A
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- metformin hydrochloride
- release tablet
- intragastric floating
- floating sustained
- octadecanol
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Abstract
The invention relates to a medicament for treating diabetes, in particular to a metformin hydrochloride intragastric floating sustained-release tablet and a preparation method thereof. By adopting a framework-type material, an aerogenic agent, a lubricant, an adhesive and other prescriptions and using a unique preparation process, the invention can overcome solve the problem that sustained-controlled-release tablets in the prior art are low in bioavailability, and provides a metformin hydrochloride intragastric floating sustained-release tablet preparation with high bioavailability.
Description
Technical field
The present invention relates to a kind of treatment diabetes medicament metformin hydrochloride intragastric floating sustained-release tablet and preparation method thereof.
Background technology
Metformin hydrochloride is a kind of biguanides oral antidiabetic drug, is used for the treatment of type ii diabetes.At present, common metformin preparation dose is excessive, and medication is frequent, after nearly 30% patient takes apparent in view side reaction is arranged, and comprises stomach discomfort, feels sick, digestive tract reactions such as anorexia, diarrhoea.
The research of diabecron sustained-release preparation has now caused extensive concern.The relevant report of at present existing oral controlled-release or slow releasing preparation.Common metformin hydrochloride slow releasing preparation discharges initial amount excessive (2 hours cumulative release percentage rate＞40%, i.e. burst effects) at gastric, has caused the stimulation to gastric mucosa, and then may cause a series of digestive tract reactions; Simultaneously since the main absorption site of metformin medicine in the small intestinal upper end, the absorbability at colon place is very weak, and common oral controlled-release or slow releasing preparation only have 2～3h mainly in the colon release in the holdup time of its absorption site, so bioavailability is low.
Summary of the invention
The objective of the invention is to overcome prominent phenomenon and the low problem of bioavailability released that causes owing to metformin hydrochloride is very easily water-soluble that the agent of metformin hydrochloride slow-release tablet exists in the prior art, a kind of slowly lasting metformin hydrochloride intragastric floating sustained-release tablet preparation that discharges medicine is provided.
Another object of the present invention provides the preparation method of above-mentioned metformin hydrochloride intragastric floating sustained-release tablet.
The intragastric floating sustained-release preparation is meant a kind of drug delivery system that may float in the gastric juice and discharge medicine in a long time with constant speed.
Metformin hydrochloride intragastric floating sustained-release tablet of the present invention, form by following weight ratio by following each component:
Metformin hydrochloride: 55%～65%;
Matrix type material: 25%～35%;
Gas generating agent: 4%～8%;
Lubricant: 0.5%～2%;
Binding agent: 0.5%～4%.
Matrix type material among the present invention is two or more in hypromellose, ethyl cellulose, sodium carboxymethyl cellulose, octadecanol, hexadecanol and the stearic acid.Preferred matrix type material is hypromellose and octadecanol, and the weight ratio of hypromellose and octadecanol is 0.5～5: 1, and comparatively preferred ratio is 0.75～2: 1.Gas generating agent is a kind of in basic magnesium carbonate or the sodium bicarbonate, preferred sodium bicarbonate.Lubricant be in magnesium stearate, Pulvis Talci, the micropowder silica gel any one or more than one.Binding agent can be the water or the alcoholic solution of polyvinylpyrrolidone, hypromellose.
The preparation method of metformin hydrochloride intragastric floating sustained-release tablet of the present invention comprises the steps:
1) it is standby that principal agent and adjuvant are all crossed 80 mesh sieves.
2) with octadecanol (or hexadecanol, stearic acid) melting, add metformin hydrochloride, stir, pulverize, cross 80 mesh sieves;
3) with 2) with all the other matrix type materials, gas generating agent mixing, add binding agent system soft material, the granulation of 18 orders;
4) 40 ℃ of dryings are 2～4 hours, granulate;
5) add lubricant, compacting in flakes behind the mixing.
Key of the present invention is octadecanol of melting (or hexadecanol, stearic acid) and metformin mix homogeneously; Can make the hydrophobic octadecanol of medicine granule surface parcel one deck on the one hand, strengthen slow release effect, solve the prominent problem of bringing owing to principal agent is very easily water-soluble of releasing; On the other hand, because " solid bridge " phenomenon that octadecanol forms in the tabletting process can improve because metformin principal agent amount is big, compressibility is bad and cause the generation of phenomenons such as sliver.
Key of the present invention adds gas generating agent in also being, makes the floating in stomach sheet.Gas generating agent is met gastric acid under one's belt and is promptly produced carbon dioxide, simultaneously owing to the rapid aquation of hydrophilic framework material, makes tablet rise rapidly and floats, thereby prolonged the tablet holdup time under one's belt; Because the main absorption site of metformin hydrochloride is a upper part of small intestine, therefore, making intragastric floating sustained-release tablet has its necessity.
Adopt the metformin hydrochloride intragastric floating sustained-release tablet preparation of the technology of the present invention preparation, float rapidly in release medium, 12 hours long-acting slow release medicines have avoided that local drug concentration is excessive to stimulate gastrointestinal; Floating in stomach time while is long, and medicine is discharged from slow releasing tablet before reaching absorption site fully, thereby reaches the purpose that improves bioavailability of medicament and blood drug level.Metformin hydrochloride intragastric floating sustained-release tablet can effectively be controlled release rate of drugs, avoids local drug concentration too high and cause stomach discomfort, can significantly improve bioavailability of medicament simultaneously.
The specific embodiment
Embodiment 1:
Prescription: metformin hydrochloride 500g;
Ethyl cellulose 124g;
Sodium carboxymethyl cellulose 40g
Stearic acid 80g;
Basic magnesium carbonate 48g;
Micropowder silica gel 4g;
Magnesium stearate 4g;
HPMC (50cps) 20% alcoholic solution is an amount of
Make 1000 altogether
Preparation method: it is standby that principal agent and adjuvant are all crossed 80 mesh sieves.At first stearic acid is heated melting, add metformin hydrochloride again, stir, pulverize, cross 80 mesh sieves; With ethyl cellulose, sodium carboxymethyl cellulose and basic magnesium carbonate mixing, add HPMC (50cps) 20% alcoholic solution system soft material, 18 orders are granulated; 40 ℃ of dryings 2 ~ 4 hours, 16 mesh sieve granulate; Add micropowder silica gel, magnesium stearate, mixing is made sheet with the capsule shape punching press.
Embodiment 2:
Prescription: metformin hydrochloride 500g;
Hydroxypropyl emthylcellulose 184g;
Hexadecanol 60g;
Sodium bicarbonate 48g;
Pulvis Talci 8g;
10%PVP (K30) alcoholic solution is an amount of
Make 1000 altogether
Preparation method: it is standby that principal agent and adjuvant are all crossed 80 mesh sieves.At first hexadecanol is heated melting, add metformin hydrochloride again, stir, pulverize, cross 80 mesh sieves; With hydroxypropyl emthylcellulose, sodium bicarbonate mixing, add 10%PVP (K30) alcoholic solution system soft material, 18 orders are granulated; 40 ℃ of dryings 2 ~ 4 hours, 16 mesh sieve granulate; Add Pulvis Talci, mixing is made sheet with the capsule shape punching press.
Embodiment 3:
Prescription: metformin hydrochloride 500g;
Hydroxypropyl emthylcellulose 100g;
Octadecanol 144g;
Sodium bicarbonate 48g;
Magnesium stearate 8g;
10%PVP (K30) alcoholic solution is an amount of
Make 1000 altogether
Preparation method: it is standby that principal agent and adjuvant are all crossed 80 mesh sieves.At first octadecanol is heated melting, add metformin hydrochloride again, stir, pulverize, cross 80 mesh sieves; With hydroxypropyl emthylcellulose, sodium bicarbonate mixing, add 10%PVP (K30) alcoholic solution system soft material, 18 orders are granulated; 40 ℃ of dryings 2 ~ 4 hours, 16 mesh sieve granulate; Add magnesium stearate, mixing is made sheet with the capsule shape punching press.
Embodiment 4:
Prescription: metformin hydrochloride 500g;
Hydroxypropyl emthylcellulose 164g;
Octadecanol 100g;
Sodium bicarbonate 48g;
Magnesium stearate 8g;
10%PVP (K30) alcoholic solution is an amount of
Make 1000 altogether
Preparation method: it is standby that principal agent and adjuvant are all crossed 80 mesh sieves.At first octadecanol is heated melting, add metformin hydrochloride again, stir, pulverize, cross 80 mesh sieves; With hydroxypropyl emthylcellulose, sodium bicarbonate mixing, add 10%PVP (K30) alcoholic solution system soft material, 18 orders are granulated; 40 ℃ of dryings 2 ~ 4 hours, 16 mesh sieve granulate; Add magnesium stearate, mixing is made sheet with the capsule shape punching press.
Embodiment 5:
Prescription: metformin hydrochloride 500g;
Hydroxypropyl emthylcellulose 220g;
Octadecanol 55g;
Sodium bicarbonate 48g;
Magnesium stearate 8g;
10%PVP (K30) alcoholic solution is an amount of
Make 1000 altogether
Preparation method: it is standby that principal agent and adjuvant are all crossed 80 mesh sieves.At first octadecanol is heated melting, add metformin hydrochloride again, stir, pulverize, cross 80 mesh sieves; With hydroxypropyl emthylcellulose, sodium bicarbonate mixing, add 10%PVP (K30) alcoholic solution system soft material, 18 orders are granulated; 40 ℃ of dryings 2 ~ 4 hours, 16 mesh sieve granulate; Add magnesium stearate, mixing is made sheet with the capsule shape punching press.
Embodiment 6:
Embodiment among the present invention 3, example 4, example 5 are carried out release in vitro degree test in 12 hours respectively with patent 200310112200.8 embodiment 1, and result of the test is compared.
Test method: according to drug release determination (two ones first method slurries of Chinese Pharmacopoeia version in 2005 method), the 900ml simulated gastric fluid is as release medium, and rotating speed is that per minute 50 changes, operation in accordance with the law, in 1h, 2h, 4h, 6h, 8h, 10h, 12h, sampling 5ml filters (release medium of in time replenishing the equal-volume equitemperature), dilution.
The external floating situation of each prescription is investigated and is seen Table one.The cumulative release percentage rate of each time point sees Table two.
The external floating situation of table one, four prescriptions of comparison
Annotate: F floats for rising, and promptly is sunken among the liquid level fully.
The average accumulated of table two, each time point of four prescriptions of comparison discharges percentage rate
By contrast, visible metformin hydrochloride intragastric floating sustained-release tablet of the present invention floats in release medium soon, rises and floats longer duration, and discharge slowly lastingly, has solved the prominent problem of bringing owing to principal agent is very easily water-soluble of releasing preferably.
In addition, because the preparation of intragastric floating sustained-release tablet of the present invention success makes it drug release at stomach, be absorbed in the small intestinal upper end, thereby can improve bioavailability.
Embodiment 7:
Prescription: metformin hydrochloride 750g;
Hydroxypropyl emthylcellulose 216g;
Octadecanol 150g;
Sodium bicarbonate 72g;
Magnesium stearate 10g;
10%PVP (K30) alcoholic solution is an amount of
Make 1000 altogether
Preparation method: it is standby that principal agent and adjuvant are all crossed 80 mesh sieves.At first octadecanol is heated melting, add metformin hydrochloride again, stir, pulverize, cross 80 mesh sieves; With hydroxypropyl emthylcellulose, sodium bicarbonate mixing, add 10%PVP (K30) alcoholic solution system soft material, 18 orders are granulated; 40 ℃ of dryings 2 ~ 4 hours, 16 mesh sieve granulate; Add magnesium stearate, mixing is made sheet with the capsule shape punching press.
Embodiment 8:
Prescription: metformin hydrochloride 1000g;
Hydroxypropyl emthylcellulose 248g;
Stearic acid 240g;
Sodium bicarbonate 96g;
Magnesium stearate 16g;
10%PVP (K30) alcoholic solution is an amount of
Make 1000 altogether
Preparation method: it is standby that principal agent and adjuvant are all crossed 80 mesh sieves.At first stearic acid is heated melting, add metformin hydrochloride again, stir, pulverize, cross 80 mesh sieves; With hydroxypropyl emthylcellulose, sodium bicarbonate mixing, add 10%PVP (K30) alcoholic solution system soft material, 18 orders are granulated; 40 ℃ of dryings 2 ~ 4 hours, 16 mesh sieve granulate; Add magnesium stearate, mixing is made sheet with the capsule shape punching press.
Claims (9)
1, a kind of metformin hydrochloride intragastric floating sustained-release tablet is characterized in that being made up of by following weight ratio following component: metformin hydrochloride: 55%～65%; Matrix type material: 25%～35%; Gas generating agent: 4%～8%; Lubricant: 0.5%～2%; Binding agent: 0.5%～4%.
2, metformin hydrochloride intragastric floating sustained-release tablet according to claim 1 is characterized in that the matrix type material is two or more in hypromellose, ethyl cellulose, sodium carboxymethyl cellulose, octadecanol, hexadecanol and the stearic acid.
3, metformin hydrochloride intragastric floating sustained-release tablet according to claim 1 and 2 is characterized in that the matrix type material is hypromellose and octadecanol, and the weight ratio of hypromellose and octadecanol is 0.5～5: 1.
4, metformin hydrochloride intragastric floating sustained-release tablet according to claim 3, the weight ratio that it is characterized in that hypromellose and octadecanol is 0.75～2: 1.
5, metformin hydrochloride intragastric floating sustained-release tablet according to claim 1 is characterized in that gas generating agent is a kind of in basic magnesium carbonate or the sodium bicarbonate.
6, metformin hydrochloride intragastric floating sustained-release tablet according to claim 5 is characterized in that gas generating agent is a sodium bicarbonate.
7, metformin hydrochloride intragastric floating sustained-release tablet according to claim 1 is characterized in that lubricant is one or more in magnesium stearate, Pulvis Talci, the micropowder silica gel.
8, metformin hydrochloride intragastric floating sustained-release tablet according to claim 1 is characterized in that binding agent is the water or the alcoholic solution of polyvinylpyrrolidone, hypromellose.
9, a kind of preparation is characterized in that comprising the following steps: as the method for the described metformin hydrochloride intragastric floating sustained-release tablet preparation of claim 1～8
1) it is standby that principal agent and adjuvant are all crossed 80 mesh sieves.
2) with octadecanol (or hexadecanol, stearic acid) melting, add metformin hydrochloride, stir, put coldly, pulverize, cross 80 mesh sieves;
3) with 2) with all the other matrix type materials, gas generating agent mixing, add binding agent system soft material, the granulation of 18 orders;
4) 40 ℃ of dryings are 2～4 hours, granulate;
5) add lubricant, compacting in flakes behind the mixing.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200810019838XA CN101536989B (en) | 2008-03-18 | 2008-03-18 | Metformin hydrochloride intragastric floating sustained-release tablet and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200810019838XA CN101536989B (en) | 2008-03-18 | 2008-03-18 | Metformin hydrochloride intragastric floating sustained-release tablet and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101536989A true CN101536989A (en) | 2009-09-23 |
| CN101536989B CN101536989B (en) | 2012-04-25 |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107898767A (en) * | 2018-01-03 | 2018-04-13 | 临沂大学 | A kind of dog diabecron sustained-release chewable tablets and preparation method thereof |
| CN108969501A (en) * | 2018-08-20 | 2018-12-11 | 奕利制药有限公司 | A kind of Metformin hydrochloride intragastric floating tablets and preparation method thereof |
| CN111450069A (en) * | 2020-04-02 | 2020-07-28 | 南京致中生物科技有限公司 | Metformin hydrochloride oral sustained-release tablet and preparation method thereof |
| CN112999182A (en) * | 2020-08-19 | 2021-06-22 | 重庆康刻尔制药股份有限公司 | Metformin hydrochloride dual sustained and controlled release composition and preparation method and application thereof |
| CN114404376A (en) * | 2022-03-16 | 2022-04-29 | 成都恒瑞制药有限公司 | Metformin hydrochloride sustained-release tablet and preparation method thereof |
-
2008
- 2008-03-18 CN CN200810019838XA patent/CN101536989B/en active Active
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107898767A (en) * | 2018-01-03 | 2018-04-13 | 临沂大学 | A kind of dog diabecron sustained-release chewable tablets and preparation method thereof |
| CN107898767B (en) * | 2018-01-03 | 2021-07-20 | 临沂大学 | Metformin hydrochloride sustained-release chewable tablet for dogs and preparation method thereof |
| CN108969501A (en) * | 2018-08-20 | 2018-12-11 | 奕利制药有限公司 | A kind of Metformin hydrochloride intragastric floating tablets and preparation method thereof |
| CN111450069A (en) * | 2020-04-02 | 2020-07-28 | 南京致中生物科技有限公司 | Metformin hydrochloride oral sustained-release tablet and preparation method thereof |
| CN112999182A (en) * | 2020-08-19 | 2021-06-22 | 重庆康刻尔制药股份有限公司 | Metformin hydrochloride dual sustained and controlled release composition and preparation method and application thereof |
| CN114404376A (en) * | 2022-03-16 | 2022-04-29 | 成都恒瑞制药有限公司 | Metformin hydrochloride sustained-release tablet and preparation method thereof |
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| Publication number | Publication date |
|---|---|
| CN101536989B (en) | 2012-04-25 |
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