CN110711183A - Compound metformin hydrochloride osmotic pump controlled release capsule and preparation method thereof - Google Patents

Compound metformin hydrochloride osmotic pump controlled release capsule and preparation method thereof Download PDF

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CN110711183A
CN110711183A CN201810810400.7A CN201810810400A CN110711183A CN 110711183 A CN110711183 A CN 110711183A CN 201810810400 A CN201810810400 A CN 201810810400A CN 110711183 A CN110711183 A CN 110711183A
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capsule
osmotic pump
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metformin hydrochloride
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胡容峰
陆文捷
高松
陈艳君
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Anhui University of Traditional Chinese Medicine AHUTCM
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Abstract

The invention relates to a compound metformin hydrochloride osmotic pump controlled release capsule and a preparation method thereof, and mainly solves the problem of controlled release of an insoluble drug gliclazide and a water-soluble drug metformin hydrochloride. The osmotic pump controlled release capsule is a compound gliclazide metformin hydrochloride three-layer osmotic pump controlled release capsule, a capsule core consists of a boosting layer in the middle and an upper drug-containing layer and a lower drug-containing layer, the capsule core is arranged in an osmotic pump controlled release capsule shell, and the top end and the lower end of the osmotic pump controlled release capsule shell are respectively provided with a drug release pore. When water enters the boosting layer, the boosting layer expands to promote the two medicines to be released from the two medicine chambers respectively. The system can realize the simultaneous zero-order release of the gliclazide and the metformin hydrochloride, obtain stable blood concentration, reduce the administration times, reduce the side effect, improve the compliance of patients and obtain better treatment effect.

Description

Compound metformin hydrochloride osmotic pump controlled release capsule and preparation method thereof
Technical Field
The invention relates to the technical field of pharmaceutical preparations, in particular to a compound metformin hydrochloride osmotic pump controlled-release capsule and a preparation method thereof.
Background
Diabetes has the characteristics of systemic metabolic diseases, is a chronic endocrine disease, various disabling or fatal acute and chronic complications caused by diabetes at present become third-class killers threatening the life health of human beings after cardiovascular diseases and malignant tumors, and the diabetes also seriously affects the life quality of patients, thereby bringing increasingly heavy economic and medical burdens to the patients and the whole society. With the continuous improvement of the living standard of people in China, the incidence rate of diabetes mellitus will continue to rise, the diabetes mellitus is a progressive disease, under the condition that the existing medical level can not radically cure the diabetes mellitus, the diabetes mellitus patients need to use antidiabetic regulating medicines, and because some patients do not ideally control blood sugar by taking a certain kind of hypoglycemic medicines alone, two or even three hypoglycemic medicines are more and more generally combined in clinic in recent years.
Metformin hydrochloride is a typical representative of biguanide drugs and is one of the most widely used hypoglycemic drugs in clinical application at present; gliclazide is a second-generation sulfonylurea long-acting oral hypoglycemic agent. The action mechanisms of the gliclazide and the metformin hydrochloride compound preparation are complementary. Gliclazide mainly corrects insulin secretion defects, improves sensitivity of surrounding tissues, and prevents synthesis of glycogen to achieve the purpose of reducing blood glucose. The metformin achieves the aim of resisting hyperglycemia by improving the sensitivity of liver and surrounding tissues to insulin and further improving the intake and utilization of insulin, and the combined application of the gliclazide and the metformin can enhance the hypoglycemic effect, reduce respective toxic and side effects to a certain extent, and reduce the dosage of each medicament and the incidence rate of gliclazide secondary failure. The metformin hydrochloride and gliclazide compound preparation needs to be taken 2-3 times a day, and the patients are inconvenient to take if the number of times of taking the preparation every day is too large, such as forgetting to take the preparation and missing the preparation, and the curative effect is influenced. Therefore, the sustained-release preparation is developed, so that the effect of the medicine is durable, the medicine taking frequency is reduced, and the medicine taking compliance of a patient can be improved.
The osmotic pump type controlled release preparation is taken as a typical representative of a sustained and controlled release preparation, and a preparation technology which takes osmotic pressure as drug release power and takes zero-order release power as a characteristic becomes a hot spot of research and development at home and abroad at present. However, the osmotic pump tablet with one chamber or a plurality of chambers has the defects of high requirement on equipment, complex preparation process, a plurality of medicament limiting factors and the like, and compared with the osmotic pump controlled release capsule, the osmotic pump controlled release capsule has obvious advantages: (1) the preparation process is relatively simple. Preparing the osmotic pump capsule shell by selecting a proper capsule material and a proper process, namely preparing the osmotic pump controlled release capsule shell by adopting a certain film-forming material and a pore-forming agent and adding a plasticizer through a glue dipping process, preparing corresponding drug release holes through mechanical or laser drilling, and sealing soluble materials on the drug release holes to prepare the capsule shell of the osmotic pump capsule; when the medicine in the capsule is filled, the medicine is mixed with a certain penetration enhancer according to the preparation principle of the capsule, and the mixture is granulated or directly mixed and filled into a capsule shell, and the capsule shell is sealed to obtain the osmotic pump capsule. The medicine and the capsule shell in the osmotic pump preparation can be separately prepared, and tabletting and coating workers are not needed in the preparation process (2). The capsule preparation process is simple, tabletting is not required, the process operation is simplified, and the production efficiency is improved. The three-layer osmotic pump preparation comprises a push layer and two drug-containing layers, and has a structure that the push layer is arranged in the middle and the drug layers are arranged on two sides. Each medicine layer is provided with a medicine release hole which is connected with the outside, and after the medicine is taken, the water in the body enters the pushing layer, and then the pushing layer expands, so that the medicine is released through the medicine release holes on the medicine layers on the two sides. Due to the unique structure, the release of the medicaments with different dissolution characteristics or different action mechanisms is favorably and synchronously controlled, and the preparation method is suitable for preparing compound preparations. At present, the domestic research on the compound metformin hydrochloride and gliclazide controlled release preparation is not reported in documents, so that the invention designs the gliclazide and the metformin hydrochloride into the compound three-layer osmotic pump controlled capsule on the basis of the research on the osmotic pump capsule shell.
Disclosure of Invention
The invention aims to provide a compound metformin hydrochloride osmotic pump controlled release capsule which is taken once a day and a preparation method thereof. The controlled release preparation is an osmotic pump controlled release capsule of compound gliclazide metformin hydrochloride, which mainly comprises an osmotic pump capsule shell and a capsule core, wherein the capsule core consists of a boosting layer in the middle and an upper drug layer and a lower drug layer, and the upper drug layer and the lower drug layer are respectively provided with a drug release pore. The invention relates to an osmotic pump controlled release capsule shell and a preparation method thereof. The osmotic pump controlled release capsule shell consists of a capsule cap and a capsule body, and the capsule shell is provided with drug release holes. The invention mainly solves the problem of controlled release of the insoluble drug gliclazide and the water-soluble drug metformin hydrochloride, and adopts the osmotic pump technology to design two drugs into a three-layer osmotic pump controlled release capsule, wherein a capsule core consists of a boosting layer in the middle and upper and lower drug layers, and the upper and lower drug layers are respectively provided with a drug release pore. When water enters the boosting layer, the boosting layer expands to promote the two medicines to be released from the two medicine chambers respectively. The system can simultaneously realize zero-order release of gliclazide and metformin hydrochloride, reduce peak valley phenomenon of blood concentration and toxic and side effects, reduce administration times and improve safety and effectiveness of the medicament; improve the compliance of patients and obtain better treatment effect.
The osmotic pump controlled release capsule of compound metformin hydrochloride is characterized in that: the osmotic pump controlled release capsule preparation is a compound three-layer osmotic pump controlled release capsule preparation, a capsule core consists of a boosting layer in the middle and an upper drug-containing layer and a lower drug-containing layer, the capsule core is filled in an osmotic pump controlled release capsule shell, the filling sequence comprises a drug-containing layer I, a boosting layer and a drug-containing layer II, and the top end and the lower end of the osmotic pump controlled release capsule shell are respectively provided with a drug release pore.
Osmotic pump controlled release capsule shell, its characterized in that: consists of a capsule cap and a capsule body, the top end of the capsule shell is provided with a drug release hole, and the diameter range of the drug release hole is as follows: 0.1 to 1.5 mm. And (4) pulling out the shell by a glue dipping process, cutting and finishing to obtain the osmotic pump capsule shell. The capsule wall material liquid consists of film forming material, pore creating agent, plasticizer, etc. The osmotic pump controlled release capsule shell comprises the following components in percentage by weight: 2-15% of film forming material, 0.5-50% of pore-forming agent and 0-30% of plasticizer.
Osmotic pump controlled release capsule shell, its characterized in that: the film forming material is selected from one or a mixture of more of cellulose acetate, ethyl cellulose, methyl cellulose, cellulose acetate phthalate hydroxypropyl methylcellulose phthalate and polyacrylic resin; the pore-forming agent is one or more plasticizers selected from PEG series, polyvidone, copovidone and hydroxypropyl cellulose, and is one or more selected from glycerol, propylene glycol, triethyl citrate, dimethyl phthalate, diethyl phthalate, dioctyl phthalate, dimethoxy ethyl phthalate, glycerol triacetate and polyethylene glycol. The solvent is one or more of propanol, isopropanol, propylene glycol, methanol, ethanol, and water.
Osmotic pump controlled release capsule shell, its characterized in that: the top of the capsule shell is provided with a drug release hole, a laser or a mechanical drill is adopted for punching, and the diameter range of the drug release hole is as follows: 0.1 to 1.5mm, preferably 0.6 to 1.0 mm. The drug release pore can be sealed by adopting a certain material to prevent the drug from leaking, and the sealing material is as follows: gelatin, acacia, hypromellose, alginate, polyvinylpyrrolidone, carbopol, croscarmellose sodium, and sodium carboxymethyl starch, preferably mixture of acetone and water.
The osmotic pump controlled release capsule of compound metformin hydrochloride is characterized in that: the metformin hydrochloride drug-containing layer can be selected from polyvinylpyrrolidone (PVP-K90), hydroxypropyl methylcellulose (HPMC)K100M) One or more than one of sodium carboxymethylcellulose (CMC-Na) is used as a drug release regulator to regulate the release of the sodium carboxymethylcellulose (CMC-Na), and PVP-K90 is preferably used as the drug release regulator in the prescription; polyoxyethylene (wsr-301, wsr-coagulant and wsr-303) with the molecular weight of 10-90 ten thousand is selected in the boosting layer in the capsule core, and finally, the PEO wsr-303 is preferably selected as a suspending agent; in the gliclazide drug-containing layer, PEO (PEO wsr-N10, PEO wsr-N80, PEO wsr-N205 and PEO wsr-N1105) with the molecular weight of 10-90 ten thousand can be selected as a suspending agent, and finally, the PEO wsr-N80 is preferably selected as the suspending agent.
The osmotic pump controlled release capsule of compound metformin hydrochloride is characterized in that: gliclazide layer prescription: 20 parts of gliclazide, 40-80 parts of polyoxyethylene (wsr-N80), 20-40 parts of Ludipress, 5-15 parts of sodium dodecyl sulfate and a proper amount of magnesium stearate; prescription of a boosting layer: 20-50 parts of sodium chloride, 40-80 parts of polyoxyethylene (wsr-303), 2-8 parts of hydroxypropyl methylcellulose and a metformin hydrochloride layer formula: 125 parts of metformin hydrochloride, 20-30 parts of PVP-K9030-50 parts of Ludipress and a proper amount of magnesium stearate.
The osmotic pump controlled release capsule of compound metformin hydrochloride is characterized in that: gliclazide layer prescription: 20 parts of gliclazide, 60 parts of polyoxyethylene (wsr-N80), 30 parts of Ludipress, 10 parts of sodium dodecyl sulfate and a proper amount of magnesium stearate; prescription of a boosting layer: 35 parts of sodium chloride, 60 parts of polyoxyethylene (wsr-303), 2 parts of hydroxypropyl methylcellulose, and a metformin hydrochloride layer formula: 125 parts of metformin hydrochloride, PVP-K9025 parts, 40 parts of Ludipress and a proper amount of magnesium stearate.
The osmotic pump controlled release capsule of compound metformin hydrochloride is characterized in that: weighing the components according to the prescription amount, uniformly mixing, respectively preparing a gliclazide layer, a boosting layer and a metformin hydrochloride layer, directly tabletting the powder, filling the powder into an osmotic pump controlled release capsule, tightly covering a capsule cap outside the capsule body, simultaneously sealing the capsule cap with capsule material liquid, and drying at room temperature.
Description of the drawings:
FIG. 1 is a schematic view of a compound metformin hydrochloride gliclazide osmotic pump controlled release capsule of the invention
FIG. 2 is the release curve of the compound metformin hydrochloride gliclazide osmotic pump controlled release gel of example 1
FIG. 3 the drug-time profile of commercially available tablets and self-made osmotic pump capsules (A metformin hydrochloride B gliclazide)
The specific implementation mode is as follows:
example 1
Preparation of compound gliclazide metformin three-layer osmotic pump controlled release capsule
1. Capsule core prescription:
gliclazide layer prescription:
Figure BSA0000167604030000041
prescription of a boosting layer:
35mg of sodium chloride
Polyoxyethylene (wsr-303)60 mg
Hydroxypropyl methylcellulose 2mg
Metformin hydrochloride layer prescription:
Figure BSA0000167604030000042
prescription of capsule material liquid:
Figure BSA0000167604030000043
2. the preparation process comprises the following steps:
preparation of the osmotic capsule shell:
(1) preparing capsule liquid, wherein polyethylene glycols are water-soluble materials, and certain water is added to dissolve the polyethylene glycols during preparation; standing to remove bubbles.
(2) And (3) dipping glue by using a glue dipping process, and when the glue is dipped for certain times, pulling out the shell, cutting and finishing to obtain the capsule shell of the positioning osmotic pump.
Preparation of compound gliclazide metformin hydrochloride osmotic pump capsule
(1) Accurately weighing the main drug powder and the auxiliary material powder which are sieved by a sieve of 80 meshes according to the prescription amount respectively, and uniformly mixing;
(2) the content powder of the prescription amount is respectively tabletted and filled into a permeable capsule shell according to a metformin hydrochloride drug-containing layer, a boosting layer and a gliclazide drug-containing layer, a capsule body and a capsule cap are buckled and sealed by a capsule material liquid, and finally, two ends of the capsule are punched.
3. Establishment of HPLC analysis method for sample in plasma
3.1 establishment of HPLC analysis method for gliclazide in plasma
3.1.1 chromatographic conditions
A chromatographic column: welch Materials XB C18Chromatography columns (Welch, 250 mm. times.4.6 mm, 5 μm); flow ofMoving phase: methanol-0.02 moL/L potassium dihydrogen phosphate (pH adjusted to 3.5 with phosphoric acid) 61: 39 (v/v); flow rate: 1.0 ml/min; detection wavelength: 227 nm; column temperature: 30 ℃; taking glipizide as an internal standard; the amount of sample was 20. mu.L.
3.1.2 methods of plasma sample processing
Precisely transferring 100 mu L of plasma sample melted at room temperature, placing the plasma sample in an EP tube, adding 300 mu L of acetonitrile, uniformly mixing, adding 100 mu L of internal standard solution and 100 mu L of gliclazide solution with different concentrations, vortexing for 1min, centrifuging for 10min at 12000 r, centrifuging twice, and taking supernatant. Blow-drying under 37 deg.C air flow, adding 200 μ L mobile phase into the residue, dissolving, mixing by vortex, filtering with 0.22 μm filter membrane, and sampling for analysis.
3.1.3 investigation of method specificity
And (3) taking blank plasma, blank plasma containing gliclazide and internal standard liquid, and plasma samples collected after administration, performing sample injection analysis under the chromatographic condition of '3.1', recording chromatograms and comparing.
3.2 establishment of HPLC analysis method for metformin hydrochloride in plasma
3.2.1 chromatographic conditions
A chromatographic column: welch Materials XB C18 column (Welch, 250 mm. times.4.6 mm, 5 μm); mobile phase: acetonitrile alcohol-0.02 mol/L potassium dihydrogen phosphate (containing 2mmol/L sodium dodecyl sulfate adjusted to pH 3.0 with phosphoric acid) 24: 76 (v/v); flow rate: 1.0 ml/min; detection wavelength: 234 nm; column temperature: 35 ℃; taking atenolol as an internal standard; the amount of sample was 20. mu.L.
3.2.2 methods of plasma sample processing
Precisely transferring 100 μ L of plasma sample melted at room temperature, placing in EP tube, adding acetonitrile 300 μ L, mixing, adding 50 μ L of internal standard working solution and 50 μ L of metformin hydrochloride solution with different concentrations, vortexing for 1min, centrifuging at 12000 r for 10min, centrifuging twice, collecting supernatant, filtering with 0.22 μm filter membrane, sampling, and analyzing[78].
3.2.3 investigation of method specificity
Taking blank plasma, blank plasma containing metformin hydrochloride with certain concentration and internal standard solution, plasma samples collected after administration and the like under the condition of 'item 3.2.2', carrying out sample injection analysis under the chromatographic conditions, recording chromatograms and comparing.
In vivo pharmacokinetics study of Beagle dogs
4.1 dosing regimens and sample Collection
The Beagle dogs 6 were randomly divided into groups a and B using a two-cycle, double crossover experimental design, fasted for 12h prior to the experiment and had free access to water. The self-made osmotic pump capsule and the commercially available ordinary tablet are directly inserted into the oral epiglottis as a complete tablet, so that the Beagle dog swallows automatically and is fed with a small amount of clear water, and water is freely drunk during the experiment. In the 1 st period, the group A takes metformin hydrochloride gliclazide tablets, and the group B takes a self-made osmotic pump capsule preparation; after administration, the tablets are common tablets for 0, 0.25, 0.5, 1, 2, 2.5, 3, 4, 6, 8, 10, 12 and 24 hours; the capsule is prepared from capsule for 0, 1, 2, 2.5, 3, 4, 6, 8, 10, 12, and 24 hr[79]Taking 4ml of forelimb venous blood, placing in a heparinized anticoagulation EP tube, centrifuging at 3000r/min for 10min, and storing in a refrigerator at-20 ℃. The cleaning period is 1 week, the test preparation and the reference preparation are administered alternately, and the second blood sampling procedure is the same as the first blood sampling procedure.
4.2 measurement of blood concentration and time curve
Blood samples are collected at various time points after a Beagle dog orally takes a commercially available metformin hydrochloride gliclazide tablet and a self-made metformin hydrochloride gliclazide osmotic pump capsule, the blood samples are treated according to the methods under the items 3.1.2 and 3.2.2, the blood concentrations of metformin hydrochloride and gliclazide are respectively measured by chromatographic pieces under the items 3.1.1 and 3.2.1, and a pharmaceutical process curve chart is drawn, and the result is shown in figure 3.
4.3 calculation of pharmacokinetic parameters and statistical data analysis
Pharmacokinetic software DAS2.0 is adopted to calculate main pharmacokinetic parameters. The results are shown in tables 4 to 5.
TABLE 1 metformin hydrochloride pharmacokinetic parameters and bioavailability
Tab.1 The pharmacokinetic parameters and bioavailability of metforminhydrochloride
Figure BSA0000167604030000071
TABLE 2 gliclazide pharmacokinetic parameters and bioavailability
Tab.2 The pharmacokinetic parameters and bioavailability ofgliclazide
Figure BSA0000167604030000072
The experimental result shows that the blood concentration of the metformin hydrochloride and the gliclazide in the self-made osmotic pump preparation is more stable than that of the commercially available common tablet, and CmaxLower than the conventional formulation, TmaxIncrease, half-life extension, MRT extension, i.e., in vivo retention time extension, and action time extension.
4.4 relative bioavailability
AUC with commercially available plain tablets0→∞For reference control, the relative bioavailability of metformin hydrochloride gliclazide transdermal pump capsules was calculated using the following formula.
Compared with the commercially available common tablets, the self-prepared metformin hydrochloride gliclazide osmotic pump capsule has the relative bioavailability of 156.38% of metformin hydrochloride and 131.14% of gliclazide, and shows that the bioavailability of the self-prepared metformin hydrochloride gliclazide osmotic pump capsule is remarkably improved.
Examples 2 to 9
Formulations 2-9 were made in the following table, with the exception of the varying components listed in the table, as with formulation 1.
Compositions and amounts of formulas 1-9
Figure BSA0000167604030000081
The preparation process comprises the following steps: same as example 1
Preparation of the osmotic capsule shell: same as example 1
The preparation of the compound gliclazide metformin hydrochloride osmotic pump capsule comprises the following steps: the same as in example 1.

Claims (9)

1. The osmotic pump controlled release capsule of compound metformin hydrochloride is characterized in that: the osmotic pump controlled release capsule preparation is a compound three-layer osmotic pump controlled release capsule preparation, a capsule core consists of a boosting layer in the middle and an upper drug-containing layer and a lower drug-containing layer, the capsule core is filled in an osmotic pump controlled release capsule shell, the filling sequence comprises a drug-containing layer I, a boosting layer and a drug-containing layer II, and the top end and the lower end of the osmotic pump controlled release capsule shell are respectively provided with a drug release pore.
2. The osmotic pump controlled release capsule shell according to claim 1, wherein: consists of a capsule cap and a capsule body, the top end of the capsule shell is provided with a drug release hole, and the diameter range of the drug release hole is as follows: 0.1 to 1.5 mm. And (4) pulling out the shell by a glue dipping process, cutting and finishing to obtain the osmotic pump capsule shell. The capsule wall material liquid consists of film forming material, pore creating agent, plasticizer, etc. The osmotic pump controlled release capsule shell comprises the following components in percentage by weight: 2-15% of film forming material, 0.5-50% of pore-forming agent and 0-30% of plasticizer.
3. The osmotic pump controlled release capsule shell according to claims 1-2, wherein: the film forming material is selected from one or a mixture of more of cellulose acetate, ethyl cellulose, methyl cellulose, cellulose acetate phthalate hydroxypropyl methylcellulose phthalate and polyacrylic resin; the pore-forming agent is one or more plasticizers selected from PEG series, polyvidone, copovidone and hydroxypropyl cellulose, and is one or more selected from glycerol, propylene glycol, triethyl citrate, dimethyl phthalate, diethyl phthalate, dioctyl phthalate, dimethoxy ethyl phthalate, glycerol triacetate and polyethylene glycol. The solvent is one or more of propanol, isopropanol, propylene glycol, methanol, ethanol, and water.
4. The osmotic pump controlled release capsule shell according to claim 1, wherein: the top of the capsule shell is provided with a drug release hole, a laser or a mechanical drill is adopted for punching, and the diameter range of the drug release hole is as follows: 0.1 to 1.5mm, preferably 0.6 to 1.0 mm. The drug release pore can be sealed by adopting a certain material to prevent the drug from leaking, and the sealing material is as follows: gelatin, acacia, hypromellose, alginate, polyvinylpyrrolidone, carbopol, croscarmellose sodium, and sodium carboxymethyl starch, preferably mixture of acetone and water.
5. The osmotic pump controlled release capsule of compound metformin hydrochloride according to claim 1, wherein: the metformin hydrochloride drug-containing layer can be selected from polyvinylpyrrolidone (PVP-K90), hydroxypropyl methylcellulose (HPMC)K100M) And one or more of sodium carboxymethylcellulose (CMC-Na) as drug release regulator for regulating release, preferably PVP-K90 as drug release regulator in prescription.
6. The osmotic pump controlled release capsule of compound metformin hydrochloride according to claim 1, wherein: polyoxyethylene (wsr-301, wsr-coagulant, wsr-303) with the molecular weight of 200-700 ten thousand is selected in the boosting layer in the capsule core, and finally, the PEO wsr-303 is preferably selected as a suspending agent; in the gliclazide drug-containing layer, PEO (PEO wsr-N10, PEO wsr-N80, PEO wsr-N205 and PEO wsr-N1105) with the molecular weight of 10-90 ten thousand can be selected as a suspending agent, and finally, the PEO wsr-N80 is preferably selected as the suspending agent.
7. The osmotic pump controlled release capsule of compound metformin hydrochloride according to claim 1, wherein: gliclazide layer prescription: 20 parts of gliclazide, 40-80 parts of polyoxyethylene (wsr-N80), 20-40 parts of Ludipress, 5-15 parts of sodium dodecyl sulfate and a proper amount of magnesium stearate; prescription of a boosting layer: 20-50 parts of sodium chloride, 40-80 parts of polyoxyethylene (wsr-303), 2-8 parts of hydroxypropyl methylcellulose and a metformin hydrochloride layer formula: 125 parts of metformin hydrochloride, 20-30 parts of PVP-K9030-50 parts of Ludipress and a proper amount of magnesium stearate.
8. The osmotic pump controlled release capsule of compound metformin hydrochloride according to claim 1, wherein: gliclazide layer prescription: 20 parts of gliclazide, 60 parts of polyoxyethylene (wsr-N80), 30 parts of Ludipress, 10 parts of sodium dodecyl sulfate and a proper amount of magnesium stearate; prescription of a boosting layer: 35 parts of sodium chloride, 60 parts of polyoxyethylene (wsr-303), 2 parts of hydroxypropyl methylcellulose, and a metformin hydrochloride layer formula: 125 parts of metformin hydrochloride, PVP-K9025 parts, 40 parts of Ludipress and a proper amount of magnesium stearate.
9. The osmotic pump controlled release capsule of compound metformin hydrochloride according to claim 1, wherein: weighing the components according to the prescription amount, uniformly mixing, respectively preparing a gliclazide layer, a boosting layer and a metformin hydrochloride layer, directly tabletting the powder, filling the powder into an osmotic pump controlled release capsule, tightly covering a capsule cap outside the capsule body, simultaneously sealing the capsule cap with capsule material liquid, and drying at room temperature.
CN201810810400.7A 2018-07-13 2018-07-13 Compound metformin hydrochloride osmotic pump controlled release capsule and preparation method thereof Pending CN110711183A (en)

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* Cited by examiner, † Cited by third party
Title
陈艳君: "复方盐酸二甲双胍—格列齐特渗透泵胶囊的研究", 《中国优秀硕士学位论文全文数据库 医药卫生科技辑》, no. 3, 15 March 2017 (2017-03-15), pages 23 - 24 *

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