CN105534929A - Trelagliptin pharmaceutical composition - Google Patents
Trelagliptin pharmaceutical composition Download PDFInfo
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- CN105534929A CN105534929A CN201510949308.5A CN201510949308A CN105534929A CN 105534929 A CN105534929 A CN 105534929A CN 201510949308 A CN201510949308 A CN 201510949308A CN 105534929 A CN105534929 A CN 105534929A
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- CN
- China
- Prior art keywords
- lieting
- bent
- compositions according
- resin
- drug
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/513—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
Abstract
The present invention relates to an oral solid preparation pharmaceutical composition using Trelagliptin as an active ingredient. First, Trelagliptin and a polacrilin potassium resin material are prepared into a pharmaceutical resin compound; and then a pharmaceutically acceptable accessory is added into the compound to prepare tablets. The prepared sample has good stability, and dissolution is not affected. The invention uses a spray drying method to prepare the pharmaceutical resin compound, and then uses the wet granulation technique to manufacture tablets. The process is simple, and easy for industrial production.
Description
Technical field
The invention belongs to field of pharmaceutical preparations, be specifically related to a kind of stable bent Ge Lieting compositions and method for preparing tablet thereof thereof.
Background technology
Bent Ge Lieting (Trelagliptin), chemistry is by name: 2-[[6-[(3R)-3-amino-piperidino]-3,4-dihydro-3-methyl-2,4-dioxy-1 (2H)-pyrimidine radicals] methyl] the fluoro-benzonitrile of-4-, structure is shown below:
Bent Ge Lieting is a kind of DPP IV (DPP-4) inhibitor taken weekly once, suppresses DPP-4, control blood sugar level by selectivity, persistence.DPP-4 is a kind of enzyme, can cause the inactivation of incretin (glucagon-like-peptide-1 (GLP-1) and glucose-dependent-insulinotropic polypeptide (GIP)), and these two kinds of incretin plays an important role in blood glucose regulation.Suppress DPP-4, blood sugar level dependency insulin secretion can be increased, thus control blood sugar level.Military field pharmacy on March 7 in 2014 is based on the efficacy and saferry data of several III clinical trial phases carried out in Japanese patients with NIDDM, and submit the new drug application of bent Ge Lieting succinate to Japanese health workfare portion, in March, 2015 gets the Green Light.
The curative effect of bent Ge Lieting all obtains confirmation in all tests, has good safety and toleration simultaneously.Bent Ge Lieting Per-Hop behavior once just effectively can control blood sugar level, can improve the compliance of patient.The novel type Ⅱdiabetes mellitus medicine of DPP-4 inhibitor to be first class by improving body self-ability control blood sugar level, can be used as single medicine, also can with other oral antidiabetic drug coupling.Its mechanism of action is unique, has not produce hypoglycemia, do not cause body weight to increase, and the unique advantage such as side effect is little, and cause the incidence rate of gastrointestinal side effect also very low, therefore this product has clinical value and the market value of excellence.
Patent CN201310056368.5 points out that bent Ge Lieting has many kinds of solids form, and different solid form all has considerable influence for formulation samples stripping and related substance.In the present invention, bent Ge Lieting and polacrilin potassium are prepared drug-resin complex jointly, effectively can solve the problem that medicine is easy to degrade, and the stripping of obtained preparation is unaffected.
Summary of the invention
The present invention is a kind of oral solid formulation being active component with bent Ge Lieting, first bent Ge Lieting and polacrilin potassium resin material are prepared drug-resin complex by this oral solid formulation, add pharmaceutically acceptable adjuvant again and prepare tablet, obtained sample stability is good, and stripping is unaffected.
Chinese medicine resin complexes of the present invention consist of bent Ge Lieting: the mass ratio of polacrilin potassium is 1:1-2, and bent Ge Lieting and polacrilin potassium are dispersed in water, then spray drying method prepares drug-resin complex.
The accepted adjuvant that in the present invention, bent Ge Lieting compositions is selected comprises filler, binding agent, disintegrating agent, lubricant etc.
In the present invention, bent Ge Lieting compositions filler is selected from one or more in Lactis Anhydrous, lactose monohydrate, mannitol, starch, microcrystalline Cellulose.
In the present invention, bent Ge Lieting adhesive of composition is selected from one or more in low viscosity hypromellose, polyvidone, copolyvidone, hydroxypropyl cellulose, gelatin, methylcellulose, starch, polyvinyl alcohol.
In the present invention, bent Ge Lieting compositions disintegrating agent is selected from one or more in carboxymethylstach sodium, low-substituted hydroxypropyl cellulose, cross-linking sodium carboxymethyl cellulose, cross-linked carboxymethyl cellulose calcium, polyvinylpolypyrrolidone.
In the present invention, bent Ge Lieting compositions lubricant is selected from one or more in magnesium stearate, stearic acid, silicon dioxide, Pulvis Talci, sodium stearyl fumarate, hydrogenated vegetable oil.
Present invention also offers the preparation method of bent Ge Lieting sheet, process is as follows:
A. bent Ge Lieting and polacrilin potassium resin are scattered in 4-5 times amount pure water according to prescription ratio, and stirring is spent the night.Adopted by dispersion liquid spray drying device to carry out drying, baking temperature is not higher than 120 DEG C, and spray velocity regulates according to drying efficiency;
B. by drug-resin complex, filler, disintegrating agent mixing, add that suitable amount of adhesive solution carries out granulating, dry, granulate;
C. convert yield, additional lubricant or disintegrating agent, always mix;
D. tabletting is carried out to total mixed granule.
Detailed description of the invention
Below by several specific embodiment, the present invention is further described, but the present invention is not by embodiment is limited.
1 dissolution determination
In the present invention, dissolution determination adopts Chinese Pharmacopoeia version in 2010 two annex dissolution methods (annex XC) the second method (paddle method) device, and with 0.1MHCl (900ml) for dissolution medium, rotating speed is 50rpm, and temperature is 37 DEG C.In stipulated time sampling 5ml (supplementing equivalent medium) simultaneously, filter, getting subsequent filtrate is need testing solution, and separately get bent Ge Lieting reference substance configuration contrast liquid, external standard method calculates the cumulative defaultlogic of different time medicine.
Embodiment 1-4
Prescription forms:
| Name of material (mg) | Effect | Embodiment 1 | Embodiment 2 | Embodiment 3 | Embodiment 4 |
| Bent Ge Lieting | Principal agent | 50 | 50 | 100 | 100 |
| Polacrilin potassium | Enclose resin | 0 | 50 | 0 | 100 |
| Mannitol | Filler | 68 | 18 | 136 | 36 |
| Microcrystalline Cellulose | Filler | 20 | 20 | 40 | 40 |
| Cross-linking sodium carboxymethyl cellulose | Disintegrating agent | 6 | 6 | 12 | 12 |
| Hydroxypropyl cellulose | Binding agent | 4.5 | 4.5 | 9 | 9 |
| Sodium stearyl fumarate | Lubricant | 1.5 | 1.5 | 3 | 3 |
Preparation technology:
A. the bent Ge Lieting of embodiment 2,4 and polacrilin potassium resin are scattered in 4-5 times amount pure water according to prescription ratio, and stirring is spent the night.Adopted by dispersion liquid spray drying device to carry out drying, baking temperature is not higher than 120 DEG C, and spray velocity regulates according to drying efficiency;
B. by drug-resin complex, filler, disintegrating agent mix homogeneously, add appropriate hydroxypropyl cellulose solution soft material, 20 orders are granulated, and 50 DEG C are dried to moisture and are less than 3%, 24 order granulate;
C. convert yield, additional lubricant, be always mixed even;
D. tabletting is carried out to total mixed granule.
The direct premix soft material of embodiment 1,3.Slice, thin piece size heavily regulates according to sheet, and tablet hardness controls at about 50N.
Carry out dissolution determination according to above-mentioned dissolution determination method to embodiment 1-4 formulation samples, result is as follows:
| Time (min) | Embodiment 1 | Embodiment 2 | Embodiment 3 | Embodiment 4 |
| 5 | 42.36 | 30.52 | 48.95 | 40.97 |
| 10 | 57.09 | 50.32 | 62.86 | 56.76 |
| 20 | 73.89 | 70.33 | 80.09 | 75.45 |
| 30 | 89.63 | 87.56 | 93.43 | 90.74 |
| 45 | 98.52 | 97.93 | 99.07 | 97.43 |
| 60 | 99.01 | 99.72 | 99.71 | 100.08 |
As can be seen from embodiment 1-4 stripping measurement result, in 30min, drug-eluting all reaches more than 85%.The amplification of tablet formulation geometric ratio has no significant effect drug-eluting, and drug-resin complex stripping and free drug stripping are without significant difference in addition, produces obviously impact to stripping after medicine is wrapped.
2 Stability Determinations
Embodiment 5-6
Prescription forms:
| Name of material (mg) | Effect | Embodiment 1 | Embodiment 2 | Embodiment 5 | Embodiment 6 |
| Bent Ge Lieting | Principal agent | 50 | 50 | 50 | 50 |
| Polacrilin potassium | Enclose resin | 0 | 50 | 100 | 150 |
| Mannitol | Filler | 68 | 18 | 18 | 18 |
| Microcrystalline Cellulose | Filler | 20 | 20 | 20 | 20 |
| Cross-linking sodium carboxymethyl cellulose | Disintegrating agent | 6 | 6 | 6 | 6 |
| Hydroxypropyl cellulose | Binding agent | 4.5 | 4.5 | 4.5 | 4.5 |
| Sodium stearyl fumarate | Lubricant | 1.5 | 1.5 | 1.5 | 1.5 |
Embodiment 5-6 preparation technology is with embodiment 2,4.
Obtained for embodiment 1,2,5,6 slice, thin piece is placed in culture dish, and in high temperature 60 DEG C ± 2 DEG C, high humidity 92.5%, place 10 days, measure each embodiment sample related substance (%) under the condition of illumination 4500 ± 500lx, investigate sample stability, result is as follows:
| Embodiment 1 | Embodiment 2 | Embodiment 5 | Embodiment 6 | |
| 0 day | 0.05 | 0.04 | 0.05 | 0.05 |
| High temperature 10 days | 1.25 | 0.35 | 0.24 | 0.22 |
| High humidity 10 days | 0.29 | 0.13 | 0.10 | 0.09 3 --> |
| Illumination 10 days | 0.10 | 0.07 | 0.04 | 0.05 |
From above-mentioned experimental result, resin complexes, to stable medicine, prevents related substance from producing and has important function.Embodiment 1 Chinese medicine dissociates, and impurity increases obviously under the high temperature conditions, and medicine is by after resin enclose, and stability increases, and impurity increasess slowly, and resin ratio increases, and is increased by enclose medicine, and stability increases.But, after resin pharmaceutical ratio is increased to 2:1, continue to increase amount of resin little on related substance impact, mainly because resin-carried medicine has reached saturated.
Claims (7)
1. with the oral solid formulation pharmaceutical composition that bent Ge Lieting is active component, it is characterized in that bent Ge Lieting and polacrilin potassium resin material adopt nebulization to prepare drug-resin complex, then add pharmaceutically acceptable adjuvant and prepare tablet.
2. bent Ge Lieting compositions according to claim 1, is characterized in that, described drug-resin complex consist of bent Ge Lieting: the mass ratio of polacrilin potassium is 1:1-2.
3. bent Ge Lieting compositions according to claim 1, it is characterized in that, described accepted adjuvant comprises filler, binding agent, disintegrating agent, lubricant etc.
4. bent Ge Lieting compositions according to claim 3, it is characterized in that, described filler is selected from one or more in Lactis Anhydrous, lactose monohydrate, mannitol, starch, microcrystalline Cellulose.
5. bent Ge Lieting compositions according to claim 3, it is characterized in that, described binding agent is selected from one or more in low viscosity hypromellose, polyvidone, copolyvidone, hydroxypropyl cellulose, gelatin, methylcellulose, starch, polyvinyl alcohol.
6. bent Ge Lieting compositions according to claim 3, is characterized in that, described disintegrating agent is selected from one or more in carboxymethylstach sodium, low-substituted hydroxypropyl cellulose, cross-linking sodium carboxymethyl cellulose, cross-linked carboxymethyl cellulose calcium, polyvinylpolypyrrolidone.
7. bent Ge Lieting compositions according to claim 3, it is characterized in that, described lubricant is selected from one or more in magnesium stearate, stearic acid, silicon dioxide, Pulvis Talci, sodium stearyl fumarate, hydrogenated vegetable oil.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510949308.5A CN105534929A (en) | 2015-12-18 | 2015-12-18 | Trelagliptin pharmaceutical composition |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510949308.5A CN105534929A (en) | 2015-12-18 | 2015-12-18 | Trelagliptin pharmaceutical composition |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN105534929A true CN105534929A (en) | 2016-05-04 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510949308.5A Pending CN105534929A (en) | 2015-12-18 | 2015-12-18 | Trelagliptin pharmaceutical composition |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113975241A (en) * | 2021-11-01 | 2022-01-28 | 宁波高新区美诺华医药创新研究院有限公司 | Preparation process of trelagliptin succinate tablets |
| CN116139092A (en) * | 2023-04-17 | 2023-05-23 | 山东新时代药业有限公司 | Viagliptin tablet and preparation method thereof |
-
2015
- 2015-12-18 CN CN201510949308.5A patent/CN105534929A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113975241A (en) * | 2021-11-01 | 2022-01-28 | 宁波高新区美诺华医药创新研究院有限公司 | Preparation process of trelagliptin succinate tablets |
| CN116139092A (en) * | 2023-04-17 | 2023-05-23 | 山东新时代药业有限公司 | Viagliptin tablet and preparation method thereof |
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| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20160504 |
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| WD01 | Invention patent application deemed withdrawn after publication |