Solid pharmaceutical preparation of a kind of novel metformin hydrochloride and preparation method thereofTechnical field
The present invention relates to field of pharmaceutical preparations, specifically refer to solid pharmaceutical preparation of a kind of novel metformin hydrochloride and preparation method thereof.
Background technology
Metformin hydrochloride is a kind of safe and effective, is subject to the medicine of market treatment diabetes certainly.First-selected type 2 diabetes mellitus of failing to respond to any medical treatment for diet-treated only and physical training, particularly fat type 2 diabetes mellitus; For 1 type or type 2 diabetes mellitus, this medicine can share with insulin, can strengthen the hypoglycemic activity of insulin, thus reduces insulin dosage, prevents hypoglycemia from occurring; This medicine also can share with sulphanylureas oral antidiabetic drug, tool synergism.
Metformin hydrochloride is mainly by oral, and then absorb in the intestines and stomach of patient, therefore its dosage form includes ordinary preparation, slow releasing preparation, enteric coated preparation etc.But existing dosage form exists significant limitation in absorption of human body, or be that oral ordinary preparation and slow releasing agent are absorbed human stomach, or be that enteric coated preparation is absorbed in human body intestinal canal.The dosage form disintegrates excessive velocities of existing medicine, because the absorbability of human body is limited, adding can only a site absorption medicine in stomach or intestinal, medicine must be caused to be fully absorbed, and therapeutic effect will be had a greatly reduced quality, in order to reach treatment concentration, then need to increase the dose taken, or shorten the cycle of taking medicine, directly increase untoward reaction odds, and the order of severity.
Existing metformin hydrochloride research direction is all the release by delaying metformin hydrochloride, use various slow releasing agent, realize the slow releasing of metformin hydrochloride in human body, thus improve its bioavailability, but because metformin hydrochloride only has stomach and the intestinal absorption of human body, and these two organs are relatively active in human body, therefore while having delayed drug release, also have high amount of drug to lose, same being difficult to improves its bioavailability.
Summary of the invention
The object of the present invention is to provide a kind of first at human stomach's release portion medicine, enter the novel metformin hydrochloride solid pharmaceutical dosage formulation that human body intestinal canal discharges most of medicine again, this novel metformin hydrochloride solid pharmaceutical dosage formulation can improve the bioavailability of metformin hydrochloride, and reduces untoward reaction odds.
Another object of the present invention is the preparation method providing a kind of above-mentioned novel metformin hydrochloride medicinal composition.
The present invention is achieved through the following technical solutions: a kind of solid pharmaceutical preparation of novel metformin hydrochloride, comprise the coating material of label and coated label, label is made up of principal agent and adjuvant, wherein principal agent is metformin hydrochloride, adjuvant comprises filler, disintegrating agent, binding agent, lubricant, it is characterized in that: represent with parts by weight, the principal agent metformin hydrochloride of label 300 ~ 800 parts, adjuvant 100 ~ 500 parts, coating material 100 ~ 300 parts, described coating material comprises stomach dissolution type polymethacrylates 5 ~ 60 parts, enteric solubility polymethacrylates 80 ~ 240 parts.
The solid pharmaceutical preparation of the novel metformin hydrochloride that the technical program provides, by the coating material be made up of 5 ~ 60 parts of stomach dissolution type polymethacrylates, 80 ~ 240 parts of enteric solubility polymethacrylates, realizes the process of film control drug release.Make metformin hydrochloride first at human stomach's release portion medicine, the medicine of release accounts for 10% ~ 20% of overall drug, then enters human body intestinal canal and discharge most of medicine.
Because metformin hydrochloride is mainly higher at the absorption rate of intestinal, therefore the metformin in the technical program mainly discharges most of medicine in human body intestinal canal, thus improve the bioavailability of metformin hydrochloride, and reduce untoward reaction odds.
In order to realize the present invention better, further, in described adjuvant, filler is calcium hydrogen phosphate, disintegrating agent is sodium carboxymethyl cellulose and low-substituted hydroxypropyl cellulose, binding agent is at least one in PVP K90 and PVP K30, and lubricant is at least one in micropowder silica gel and magnesium stearate.
In order to realize the present invention better, further, described coating material also comprises plasticizer 2 ~ 5 parts, antiplastering aid 2 ~ 5 parts, and described plasticizer is triethyl citrate, and antiplastering aid is Pulvis Talci.
In order to realize the present invention better, further, the molecular mass of described stomach dissolution type polymethacrylates is 30000 ~ 47000g/mol.
In order to realize the present invention better, further, the molecular mass of described enteric solubility polymethacrylates is 123000 ~ 800000g/mol.
A preparation method for the solid pharmaceutical preparation of novel metformin hydrochloride, comprises the following steps:
(1) principal agent metformin hydrochloride is mixed homogeneously with the filler in adjuvant, disintegrating agent, make soft material with the aqueous solution of binding agent in adjuvant;
(2) with 10 ~ 24 mesh sieve corning, be then placed in the environment of 45 ~ 65 DEG C, drying is carried out to soft material;
(3) when being dried to the moisture in soft material 3% ~ 5% time, adding the lubricant in adjuvant, making its mix homogeneously, be then pressed into label;
(4) coating material is mixed in water, makes aqueous dispersions and coating is carried out to label, make label wrap up coating membrane, and increase weight 5% ~ 20%, be i.e. the solid pharmaceutical preparation of this novel metformin hydrochloride obtained.
In described step (1), principal agent metformin hydrochloride is mixed homogeneously with the filler in adjuvant, disintegrating agent, further, be that principal agent metformin hydrochloride is mixed homogeneously with the calcium hydrogen phosphate in adjuvant, sodium carboxymethyl cellulose and low-substituted hydroxypropyl cellulose; Making soft material with the aqueous solution of binding agent in adjuvant, further, is make soft material with the aqueous solution of the PVP K90 in adjuvant and at least one in PVP K30.
In described step (3), adding the lubricant in adjuvant, further, is add the micropowder silica gel in adjuvant and at least one in magnesium stearate.
In order to realize method of the present invention better, further, in described step (3), the shape of label is circular or oval.
In order to realize method of the present invention better, further, in described step (4), the thickness of coating membrane is 40 ~ 50 μm.
The present invention compared with prior art, has the following advantages and beneficial effect:
Instant invention overcomes existing metformin hydrochloride preparation can only in the limitation of gastric or the single absorption of intestinal, make first to discharge medicine human stomach, enter the novel metformin hydrochloride solid pharmaceutical preparation of human body intestinal canal release medicine again, this novel solid pharmaceutical preparation can improve the bioavailability of metformin hydrochloride, and reduce untoward reaction odds, make the release that medicine is kept in balance within a certain period of time, realize medicine to be absorbed continually and steadily, the stable of long period and effective blood drug level can be maintained, realize the optimum therapeuticing effect of medicine, give full play to Drug therapy effect.
Accompanying drawing explanation
Fig. 1 is the solid pharmaceutical preparation described in the present invention and commercial preparation drug release characteristics curve.
Detailed description of the invention
Below in conjunction with embodiment, the present invention is described in further detail, but embodiments of the present invention are not limited thereto, without departing from the idea case in the present invention described above, according to ordinary skill knowledge and customary means, make various replacement and change, all should comprise within the scope of the invention.
Embodiment 1:
The preparation method of the solid pharmaceutical preparation of a kind of novel metformin hydrochloride of the present embodiment adopts the preparation of pharmaceuticals industry known method, and the concrete consumption of each component sees table 1:
Table one
Concrete preparation method, preparation, after metformin hydrochloride, calcium hydrogen phosphate, sodium carboxymethyl cellulose, low-substituted hydroxypropyl cellulose mix homogeneously, adds in the aqueous solution of PVP K90, stirs and makes soft material.
Soft material becomes wet granular by 18 sieve series, by wet granular in the environment of 50 ~ 60 DEG C, after the moisture 3% ~ 5% that it is dried to wet granular, adds micropowder silica gel mix homogeneously, and by 0.2g/ sheet tabletted, this is plain sheet to be coated.
Gastric solubleness polymethacrylates, enteric polymethacrylates, citric acid three fat, Pulvis Talci are added to the water dispersed with stirring simultaneously and are mixed with coating solution, the plain sheet coating solution prepared coating in ordinary coating pot, concrete coating parameter is:
Sheet bed tempertaure: 25 ~ 35 DEG C; Leaving air temp: 33 ~ 40 DEG C; Hydrojet speed: 3 ~ 6g/min/kg, i.e. 0.6 ~ 1.2g/min; Coating weight gain: 20%.
Embodiment 2:
The preparation method of the solid pharmaceutical preparation of a kind of novel metformin hydrochloride of the present embodiment adopts the preparation of pharmaceuticals industry known method, and the concrete consumption of each component sees table 2:
Table two
Concrete preparation method is with embodiment 1, and concrete coating parameter is:
Sheet bed tempertaure: 25 ~ 35 DEG C; Leaving air temp: 33 ~ 40 DEG C; Hydrojet speed: 3 ~ 6g/min/kg, i.e. 2.4 ~ 5g/min; Coating weight gain: 15%.
Embodiment 3:
The preparation method of the solid pharmaceutical preparation of a kind of novel metformin hydrochloride of the present embodiment adopts the preparation of pharmaceuticals industry known method, and the concrete consumption of each component sees table 3:
Table three
The same above-described embodiment of concrete preparation method, concrete coating parameter is:
Sheet bed tempertaure: 25 ~ 35 DEG C; Leaving air temp: 33 ~ 40 DEG C, hydrojet speed: 3 ~ 6g/min/kg, i.e. 3.75 ~ 7.5g/min, coating weight gain: 10%.
Embodiment 4:
The solid pharmaceutical preparation getting novel metformin hydrochloride prepared by above-mentioned three embodiments compares with commercial preparation drug release characteristics.
Measure 0.1mol/l hydrochloric acid solution 750ml as stomach dissolution medium, medium temperature is constant in 37 ± 0.5 DEG C, start stirring arm by 100 revs/min and stir 120 minutes, respectively at 15min, 30min, 60min, 90min, 120min, 150min, 180min sampling and measuring stripping quantity, assay method is undertaken by method under Chinese Pharmacopoeia 2010 years version metformin hydrochloride enteric-coated capsules assay items; Regulate dissolution medium PH to 6.8 with 2mol/l sodium hydroxide solution after 120min, continue to continue to stir by stirring 100 revs/min, and respectively at 150min, 180min minute sampling and measuring, result be as table 4:
Table four
As shown in Figure 1, embodiment 1 ~ 3 Chinese medicine is regular release, no matter be at stomach dissolution type dissolution medium, or enteric solubility release medium Chinese medicine is all in regular stripping, and commercially available glucophage is owing to being gastric soluble tablet, it is also all disintegrate strippings in 30 minutes in dissolution medium, in enteric solubility release medium, do not have drug-eluting.
Although illustrate and describe embodiments of the invention, those having ordinary skill in the art will appreciate that: do not departing under principle of the present invention and aim and can carry out multiple change, amendment, replacement and modification to these embodiments, scope of the present invention is by claim and equivalents thereof.