CN105232490A - Metformin hydrochloride sustained release tablet and preparation method thereof - Google Patents

Abstract

The invention discloses a metformin hydrochloride sustained release tablet. The tablet is prepared from, by weight, metformin hydrochloride, lauryl sodium sulfate, polyethylene glycol 400, hydroxypropyl methylcellulose, povidone, talcum powder, cellulose acetate, polyethylene glycol 6000, triethyl citrate, titanium dioxide and magnesium stearate. The invention discloses a preparation method of the metformin hydrochloride sustained release tablet at the same time. The method includes the steps of screening and mixing raw materials, conducting granulating and tabletting on the materials, conducting primary packaging, drying, drilling, secondary packaging, drying, subpackaging and packaging, and putting products into storage. The tablet has the advantages of being simple in technological process and good in sustained release effect.

Description

A kind of diabecron sustained-release tablet and preparation method thereof

Technical field

The present invention relates to chemical medicine field, particularly relate to a kind of diabecron sustained-release tablet and preparation method thereof.

Background technology

Diabetes be in a kind of body insulin relatively or definitely not enough or target cell insulin sensitivity is reduced, or a kind of chronic disease of carbohydrate, fat and protein metabolism disorder that insulin itself exists structural defect and causes.Its main feature is hyperglycemia, glycosuria.Clinical signs is polydipsia, polyphagia, polyuria and lose weight (i.e. three-many-one-little), some tissues or organ generation morphosis can be made to change and dysfunction, concurrent ketoacidosis, extremity gangrene, polyneuritis, blind and renal failure etc.Long-standing hyperglycemia during diabetes, causes various tissue, particularly eye, kidney, heart, blood vessel, neural chronic lesion, dysfunction.Primary disease sickness rate increases day by day, the commonly encountered diseases that become international, frequently-occurring disease.

The Drug therapy of diabetes mainly contains following several:

(1) sulfonylurea drugs: 2 type DM patients are through diet control, and motion, after reducing the treatments such as body weight, curative effect is still unsatisfied with all available sulfonylurea drugs of person.Because blood sugar lowering mechanism mainly stimulates insulin secretion, so better to there being certain islet function person curative effect.To some age of onset comparatively gently, the diabetics that the bodily form is not fat also has certain curative effect in early days.But when sulfonylurea drugs uses to overweight people, diet control be paid special attention to, body weight is declined gradually, with biguanides or the coupling of alpha-glucosidase inhibitor antidiabetic drug better.Following situations belongs to contraindication: one is that serious Liver and kidney function is incomplete; Two is severe infections, during wound and major operation, uses insulinize instead temporarily; Three be Diabetic ketosis, ketoacidosis during, use insulinize instead temporarily; Four is pregnant diabetic women, gestation hyperglycemia has teratogenesis shape to act on to fetus, premature labor, stillbirth incidence rate are high, therefore answer strict glycemic control, should fasting glucose be controlled at 105 milligrams/deciliter (5.8 mM/ls) below, 2 hours blood glucoses control at 120 milligrams/deciliter (6.7 mM/ls) below after the meal, but control blood glucose should not use oral antidiabetic drug; Five are irritated to sulfonylurea drugs or occur obvious adverse reaction.

(2) biguanides: hypoglycemic main mechanism increases peripheral tissues to the utilization of glucose, increases the anerobic glycolysis of glucose, reduces gastrointestinal tract to the absorption of glucose, reduce body weight.1. indication obese type type 2 diabetes mellitus, the alone Diet Therapy effect person of being unsatisfied with; Type 2 diabetes mellitus alone sulfonylurea drugs effect is bad, can add biguanides; Type 1 diabetes insulinize unstable condition, can reduce insulin dose with biguanides; When type 2 diabetes mellitus secondary failure uses insulinize instead, can add with biguanides, can insulin dosage be reduced.2. the serious liver of contraindication, kidney, the heart, lung disease, wasting diseases, malnutrition, ischemic disease; Diabetic ketosis, ketoacidosis; Biguanides stress be suspended during situation with severe infections, operation, wound etc., use insulinize instead; Trimester of pregnancy.3. untoward reaction one is gastrointestinal reaction.The most common, show as Nausea and vomiting, appetite decline, stomachache, diarrhoea, incidence rate can reach 20%.For avoiding these untoward reaction, should take medicine in meal or after the meal.Two is headache, dizzy, metallic taste.Three is lactic acidosis, and be more common in long-term, extensive application insoral, go down with Liver and kidney function, ischemic disease, when actute infection, gastroenteropathy, metformin causes acidosic chance less.

(3) α glucosidase inhibitor: 1 type and type 2 diabetes mellitus all can use, can with sulphanylureas, biguanides or insulin coupling.1. voglibose is at once oral before the meal.2. acarbose is at once oral before the meal.Main adverse reaction has: stomachache, intestinal tympanites, diarrhoea, passage of gas by anus increase.

(4) euglycemic agent: have enhancing insulin action, improve carbohydrate metabolism.Can be alone, also can use sulphanylureas, biguanides or insulin coupling.Hepatopathy or cardiac insufficiency person person is had to apply.

(5) meglitinide Insulin secretagogues 1. repaglinide be quick Drugs Promoting Insulin Secretion, at once oral before the meal, take during each dinner, disobedience of not having meal.2. Nateglinide effect is similar to repaglinide.

Metformin hydrochloride be a kind of can the oral and biguanides of being used widely, it is the unique oral biguanides hyperglycemia medicine that current World Developed Countries is still using, the tolerance of type-II diabetes patient to sugar can be improved, reduce basis and Post-prandial plasma glucose concentration, mechanism of action is different from other antidiabetic medicines.Metformin hydrochloride reduces glycogen and generates, and small intestinal is reduced the absorption of sugar, by increase periphery, the picked-up of sugar and utilization is improved to the opposing of insulin.In normal person and type-II diabetes patient, do not produce hypoglycemic reaction, also do not produce hyperinsulinemia.The metformin hydrochloride used clinically is at present conventional tablet and capsule etc., and common dose is 1.5g every day, divides and takes for three times.Therefore, must be spaced apart regularly by medicine time, there is clothes for patients inconvenience, easily forget clothes, miss, the shortcomings such as blood concentration fluctuation is large in guarantee blood drug level maintaining treatment level.

Because metformin hydrochloride is the good medicine of a kind of water solublity, and dosage is larger, therefore, make slow releasing tablet and have great difficulty, slow-release material hydroxypropyl emthylcellulose, sodium carboxymethyl cellulose etc. that current employing is common, slow-release material use amount is excessive, cause sheet great, slow release index does not reach quality regulation in American Pharmacopeia USP32 standard yet, particularly needs control steadily to discharge with certain speed in 24 hours, maintaining stable blood drug level, to make it to reach good therapeutic effect be comparatively difficulty.

Chinese patent CN101380311B discloses a kind of diabecron sustained-release tablet, by percentage by weight be the metformin hydrochloride of 68%, the pharmaceutic adjuvant of the slow-release material of 18-22% and surplus makes, wherein said slow-release material selects hypromellose K100 and the combination of Glyceryl Behenate proportioning, and hypromellose K100 with the weight ratio with Glyceryl Behenate is: 1:0.1-0.5.The operation of this invented technology is extremely inconvenient, and said preparation is also difficult to reach the object controlling medicine and steadily discharge with certain speed.

Chinese patent CN102440975B discloses a kind of diabecron sustained-release tablet, it is characterized in that, is made up for every 10000: metformin hydrochloride 5000g of the crude drug of following weight and adjuvant; Hypromellose 1750g; Sodium carboxymethyl cellulose 1750g; Stearic acid 180g; Magnesium stearate 200g; 75% appropriate amount of ethanol.This invention slow release effect is poor, poor to patient outcomes.

Summary of the invention

High in order to solve metformin hydrochloride tablet formulation cost, complex process, the problem of slow release effect difference, we have proposed a kind of diabecron sustained-release tablet and preparation method thereof, adopts the present invention can reach technological process simple, the object of had good sustained release effect.

The present invention is achieved by the following technical solutions:

For achieving the above object, the invention provides a kind of diabecron sustained-release tablet, be made up of the crude drug of following weight and adjuvant for every 10000:

Metformin hydrochloride: 500g, main constituent.

Sodium lauryl sulphate: 5g, as emulsifying agent, granulates the emulsifying of main constituent metformin hydrochloride.

PEG400: 2g, the Polyethylene Glycol that relative molecular weight is lower can be used as solvent, cosolvent, O/W type emulsifying agent and stabilizing agent, agent, Emulsion, injection etc. are hanged for making cement, also water-soluble ointment base and suppository base is used as, for medicine not diffluent in water, this product can make the carrier of solid dispersion, to reach solid dispersal object

Hypromellose: 12g, slow release, the effect of polymerization.

Polyvidone: 40g, polyvidone a kind of water misciblely has efficient fusible synthetic polymer, mainly as the binding agent of solid preparation wet granulation, its special performance makes to become and important excipient in the application of various oral liquid, suspensoid and locality drug development.

Pulvis Talci: 5g, for medicine, food service industry additive, have nontoxic, tasteless, whiteness is high, capacitive is good, glossiness is strong, taste is soft, the strong feature of smoothness.

Cellulose acetate: 30g, for the enteric coating, acetate fiber filter membrane etc. of pharmacy product.

Polyethylene glycol 6000: 3g, the viscosity that the solid waxy Polyethylene Glycol that relative molecular weight is high is usually used in increasing low-molecular-weight liquid PEG with become solidity, and repay other drug outward.

Triethyl citrate: 2g, is mainly used as the plasticizer of adhesive and sealant.

Titanium dioxide: 10g.

Magnesium stearate: 5g.

The present invention provides a kind of preparation method of diabecron sustained-release tablet simultaneously, comprises the following steps:

(1) raw material sieves mixing: metformin hydrochloride and sodium lauryl sulphate are crossed 60 mesh sieves, mix and blend.

(2) granulate: add in mixed raw material by polyvidone aqueous solution by fluid bed, cross 60 mesh sieves, granulate, measures each constituent content.

(3) tabletting: the label medicated layer adopting bi-layer tablet press to prepare above-mentioned, label boosting layer granule suppress double-deck label, and tablet hardness is 6-14kg/mm, and Stress control is at 80-90N.

(4) first time coating: take cellulose acetate, Polyethylene Glycol, triethyl citrate acetone soln, be placed in coating pan, label is preheated to 30-50 DEG C, hydrojet coating, adjustment air feed makes sheet bed tempertaure remain on 35-40 DEG C, and coating terminates rear coating pan continuation rotation and namely obtains coated tablet in 5-10 minute.

(5) dry punching: add hypromellose, Polyethylene Glycol, Pulvis Talci, titanium dioxide aqueous suspension and magnesium stearate, proceed in HighefficientFluidbeddrier, inlet temperature 50 DEG C is set, leaving air temp 30 DEG C, drying time 8-15 minute; Break into the aperture of 0.4-0.8mm on the surface of coated tablet with laser-beam drilling machine.

(6) second time coating: in coating pan, label is preheated to 30-50 DEG C, hydrojet coating, adjustment air feed makes sheet bed tempertaure remain on 35-40 DEG C, and coating terminates rear coating pan continuation rotation and namely obtains coated tablet in 5-10 minute; Finished product is tested.

(7) dry: under 60 DEG C of conditions, drying is cured for more than 2 hours.

(8) subpackage, packaging, warehouse-in, after point granule bag mercerized towel wiped clean installed, can carry out capsule packaging, flow package is: box-vanning-joint sealing in dress capsule-dress.

Preferably, ambient temperature when above-mentioned steps (1) to (3) is carried out is 18-26 DEG C, humidity 50-70%.

Compared with prior art, beneficial effect of the present invention is:

1, technological process is simple, had good sustained release effect.

Accompanying drawing explanation

Fig. 1: the preparation method sketch of diabecron sustained-release tablet.

Detailed description of the invention

Below in conjunction with embodiment, further illustrate content of the present invention.Should be appreciated that enforcement of the present invention is not limited to the following examples, any pro forma accommodation make the present invention or change all fall into scope; And the method in following embodiment, if no special instructions, be the conventional method of this area.

Embodiment 1:

A kind of diabecron sustained-release tablet, production stage is as follows:

(1) raw material takes: be made up of the crude drug of following weight and adjuvant for every 10000:

Metformin hydrochloride: 500g;

Sodium lauryl sulphate: 5g;

PEG400: 2g;

Hypromellose: 12g;

Polyvidone: 40g;

Pulvis Talci: 5g;

Cellulose acetate: 30g;

Polyethylene glycol 6000: 3g;

Triethyl citrate: 2g;

Titanium dioxide: 10g;

Magnesium stearate: 5g.

(2) raw material sieves mixing: metformin hydrochloride and sodium lauryl sulphate are crossed 60 mesh sieves, mix and blend.

(3) granulate: add in mixed raw material by polyvidone aqueous solution by fluid bed, cross 60 mesh sieves, granulate, measures each constituent content.

(4) tabletting: the label medicated layer adopting bi-layer tablet press to prepare above-mentioned, label boosting layer granule suppress double-deck label, and tablet hardness is 6-14kg/mm, and Stress control is at 80-90N.

(5) first time coating: take cellulose acetate, Polyethylene Glycol, triethyl citrate acetone soln, be placed in coating pan, label is preheated to 30-50 DEG C, hydrojet coating, adjustment air feed makes sheet bed tempertaure remain on 35-40 DEG C, and coating terminates rear coating pan continuation rotation and namely obtains coated tablet in 5-10 minute.

(6) dry punching: add hypromellose, Polyethylene Glycol, Pulvis Talci, titanium dioxide aqueous suspension and magnesium stearate, proceed in HighefficientFluidbeddrier, inlet temperature 50 DEG C is set, leaving air temp 30 DEG C, drying time 8-15 minute; Break into the aperture of 0.4-0.8mm on the surface of coated tablet with laser-beam drilling machine.

(7) second time coating: in coating pan, label is preheated to 30-50 DEG C, hydrojet coating, adjustment air feed makes sheet bed tempertaure remain on 35-40 DEG C, and coating terminates rear coating pan continuation rotation and namely obtains coated tablet in 5-10 minute; Finished product is tested.

(8) dry: under 60 DEG C of conditions, drying is cured for more than 2 hours.

(9) subpackage, packaging, warehouse-in, after point granule bag mercerized towel wiped clean installed, can carry out capsule packaging, flow package is: box-vanning-joint sealing in dress capsule-dress.

Claims (3)

1. a diabecron sustained-release tablet, is characterized in that, is made up for every 10000 of the crude drug of following weight and adjuvant:

2. a preparation method for diabecron sustained-release tablet, is characterized in that, comprises the following steps:

(1) raw material sieves mixing: metformin hydrochloride and sodium lauryl sulphate are crossed 60 mesh sieves, mix and blend;

(2) granulate: add in mixed raw material by polyvidone aqueous solution by fluid bed, cross 60 mesh sieves, granulate, measures each constituent content;

(3) tabletting: the label medicated layer adopting bi-layer tablet press to prepare above-mentioned, label boosting layer granule suppress double-deck label, and tablet hardness is 6-14kg/mm, and Stress control is at 80-90N;

(4) first time coating: take cellulose acetate, Polyethylene Glycol, triethyl citrate acetone soln, be placed in coating pan, label is preheated to 30-50 DEG C, hydrojet coating, adjustment air feed makes sheet bed tempertaure remain on 35-40 DEG C, and coating terminates rear coating pan continuation rotation and namely obtains coated tablet in 5-10 minute;

(5) dry punching: add hypromellose, Polyethylene Glycol, Pulvis Talci, titanium dioxide aqueous suspension and magnesium stearate, proceed in HighefficientFluidbeddrier, inlet temperature 50 DEG C is set, leaving air temp 30 DEG C, drying time 8-15 minute; Break into the aperture of 0.4-0.8mm on the surface of coated tablet with laser-beam drilling machine;

(6) second time coating: in coating pan, label is preheated to 30-50 DEG C, hydrojet coating, adjustment air feed makes sheet bed tempertaure remain on 35-40 DEG C, and coating terminates rear coating pan continuation rotation and namely obtains coated tablet in 5-10 minute; Finished product is tested;

(7) dry: under 60 DEG C of conditions, drying is cured for more than 2 hours;

(8) subpackage, packaging, warehouse-in, after point granule bag mercerized towel wiped clean installed, can carry out capsule packaging, flow package is: box-vanning-joint sealing in dress capsule-dress.

3. a kind of diabecron sustained-release tablet preparation method according to claim 2, is characterized in that, ambient temperature when described step (1) to (3) is carried out is 18-26 DEG C, humidity 50-70%.