CN1568948A - Venlafaxine hydrochloride drop pills and preparation method thereof - Google Patents
Venlafaxine hydrochloride drop pills and preparation method thereof Download PDFInfo
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- CN1568948A CN1568948A CN 200410044438 CN200410044438A CN1568948A CN 1568948 A CN1568948 A CN 1568948A CN 200410044438 CN200410044438 CN 200410044438 CN 200410044438 A CN200410044438 A CN 200410044438A CN 1568948 A CN1568948 A CN 1568948A
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- CN
- China
- Prior art keywords
- venlafaxine hcl
- preparation
- coolant
- hcl
- venlafaxine
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- 239000006187 pill Substances 0.000 title claims abstract description 17
- 238000002360 preparation method Methods 0.000 title claims description 13
- 229960002416 venlafaxine hydrochloride Drugs 0.000 title abstract 2
- QYRYFNHXARDNFZ-UHFFFAOYSA-N venlafaxine hydrochloride Chemical compound [H+].[Cl-].C1=CC(OC)=CC=C1C(CN(C)C)C1(O)CCCCC1 QYRYFNHXARDNFZ-UHFFFAOYSA-N 0.000 title abstract 2
- 229960004688 venlafaxine Drugs 0.000 claims description 32
- PNVNVHUZROJLTJ-UHFFFAOYSA-N venlafaxine Chemical compound C1=CC(OC)=CC=C1C(CN(C)C)C1(O)CCCCC1 PNVNVHUZROJLTJ-UHFFFAOYSA-N 0.000 claims description 32
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 claims description 12
- 239000002826 coolant Substances 0.000 claims description 12
- 238000001035 drying Methods 0.000 claims description 8
- 229940093429 polyethylene glycol 6000 Drugs 0.000 claims description 8
- 239000000843 powder Substances 0.000 claims description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 8
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 claims description 6
- 229940008099 dimethicone Drugs 0.000 claims description 6
- 235000013870 dimethyl polysiloxane Nutrition 0.000 claims description 6
- 239000004205 dimethyl polysiloxane Substances 0.000 claims description 6
- TZBAVQKIEKDGFH-UHFFFAOYSA-N n-[2-(diethylamino)ethyl]-1-benzothiophene-2-carboxamide;hydrochloride Chemical compound [Cl-].C1=CC=C2SC(C(=O)NCC[NH+](CC)CC)=CC2=C1 TZBAVQKIEKDGFH-UHFFFAOYSA-N 0.000 claims description 6
- 229960000502 poloxamer Drugs 0.000 claims description 6
- 229920001983 poloxamer Polymers 0.000 claims description 6
- 229920000435 poly(dimethylsiloxane) Polymers 0.000 claims description 6
- 239000000758 substrate Substances 0.000 claims description 6
- 238000002156 mixing Methods 0.000 claims description 5
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 4
- 239000011159 matrix material Substances 0.000 claims description 4
- IQXJCCZJOIKIAD-UHFFFAOYSA-N 1-(2-methoxyethoxy)hexadecane Chemical compound CCCCCCCCCCCCCCCCOCCOC IQXJCCZJOIKIAD-UHFFFAOYSA-N 0.000 claims description 2
- 239000001828 Gelatine Substances 0.000 claims description 2
- 241000238631 Hexapoda Species 0.000 claims description 2
- 235000021355 Stearic acid Nutrition 0.000 claims description 2
- 239000002253 acid Substances 0.000 claims description 2
- 230000001476 alcoholic effect Effects 0.000 claims description 2
- 229950009789 cetomacrogol 1000 Drugs 0.000 claims description 2
- HPXRVTGHNJAIIH-UHFFFAOYSA-N cyclohexanol Chemical compound OC1CCCCC1 HPXRVTGHNJAIIH-UHFFFAOYSA-N 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- 229920000159 gelatin Polymers 0.000 claims description 2
- 235000019322 gelatine Nutrition 0.000 claims description 2
- YQEMORVAKMFKLG-UHFFFAOYSA-N glycerine monostearate Natural products CCCCCCCCCCCCCCCCCC(=O)OC(CO)CO YQEMORVAKMFKLG-UHFFFAOYSA-N 0.000 claims description 2
- 235000011187 glycerol Nutrition 0.000 claims description 2
- 229960005150 glycerol Drugs 0.000 claims description 2
- SVUQHVRAGMNPLW-UHFFFAOYSA-N glycerol monostearate Natural products CCCCCCCCCCCCCCCCC(=O)OCC(O)CO SVUQHVRAGMNPLW-UHFFFAOYSA-N 0.000 claims description 2
- 229940057995 liquid paraffin Drugs 0.000 claims description 2
- -1 liquid paraffin Substances 0.000 claims description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 claims description 2
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 claims description 2
- 229940093430 polyethylene glycol 1500 Drugs 0.000 claims description 2
- RYYKJJJTJZKILX-UHFFFAOYSA-M sodium octadecanoate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC([O-])=O RYYKJJJTJZKILX-UHFFFAOYSA-M 0.000 claims description 2
- 229940080350 sodium stearate Drugs 0.000 claims description 2
- 239000008117 stearic acid Substances 0.000 claims description 2
- 239000000126 substance Substances 0.000 claims description 2
- 235000015112 vegetable and seed oil Nutrition 0.000 claims description 2
- 239000008158 vegetable oil Substances 0.000 claims description 2
- 239000001993 wax Substances 0.000 claims description 2
- 238000000034 method Methods 0.000 abstract description 12
- 238000004519 manufacturing process Methods 0.000 abstract description 4
- 208000019505 Deglutition disease Diseases 0.000 abstract description 3
- 239000003814 drug Substances 0.000 abstract description 2
- 239000002671 adjuvant Substances 0.000 abstract 1
- 230000000694 effects Effects 0.000 abstract 1
- 238000004090 dissolution Methods 0.000 description 19
- 238000001514 detection method Methods 0.000 description 6
- 239000002775 capsule Substances 0.000 description 4
- 229940075507 glyceryl monostearate Drugs 0.000 description 4
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 238000010521 absorption reaction Methods 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 239000002207 metabolite Substances 0.000 description 3
- 238000004891 communication Methods 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 239000013558 reference substance Substances 0.000 description 2
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 1
- 206010062237 Renal impairment Diseases 0.000 description 1
- 230000001430 anti-depressive effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 235000019636 bitter flavor Nutrition 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 238000011978 dissolution method Methods 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 229960002748 norepinephrine Drugs 0.000 description 1
- SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 231100000857 poor renal function Toxicity 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 210000000225 synapse Anatomy 0.000 description 1
Landscapes
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention discloses am venlafaxine hydrochloride drop pill prepared through ultramicro disintegration and drop pills manufacturing technique, which has the advantages of improving collapse and dissolving speed, dissolving out speed and degree, quick effect, increased medicament stability, reduced adjuvant consumption, lowered production costs, and easiness in carrying and use. It has good compliance, thus is especially suitable for children, the elderly, bedridden patients and dysphagia patients.
Description
Technical field
The present invention relates to a kind of pharmaceutical product and preparation method thereof, specifically VENLAFAXINE HCL drop pill and preparation method thereof.
Background technology
VENLAFAXINE HCL is mainly by suppressing the reuptake of central nervous system to 5-hydroxy tryptamine and noradrenaline, make between synapse in these two kinds of monoamine neurotransmitter concentration increase the performance antidepressant effect.
The VENLAFAXINE HCL oral absorption is rapid, during single dose administration, only has 12.6% to enter circulation, and food does not have influence to the absorption of VENLAFAXINE HCL and metabolite thereof.t
1/2Average out to 4 hours, apparent volume of distribution are 6L/kg, and main metabolic is at liver, and former medicine and metabolite major part thereof are by renal excretion.Impaired renal function makes venlafaxine and its metabolite approximately reduce by 55%, and the elimination half-life obviously prolongs.List marketing at present VENLAFAXINE HCL capsule, the clinical depression that is used for only arranged.
The VENLAFAXINE HCL mildly bitter flavor, very easily dissolving in water, but its capsule disintegration time is long, dissolution and dissolution rate are low, absorption difference, and bioavailability is low, the supplementary product consumption ratio is big, child, old people, bed patient and dysphagia patients are taken inconvenience, and compliance is poor, have influenced the performance of VENLAFAXINE HCL therapeutical effect.
The present invention makes the VENLAFAXINE HCL drop pill by using ultramicro communication technique and dropping pill formulation Technology exactly, thereby overcomes the capsular above defective of VENLAFAXINE HCL, and the therapeutical effect of VENLAFAXINE HCL is given full play to.
Summary of the invention
The VENLAFAXINE HCL drop pill of making by using ultramicro communication technique and dropping pill formulation Technology not only have disintegrate molten loose fast, dissolution and dissolution rate improve, steady quality, the pill volume is little, easy to carry and use, onset is rapid, compliance is good, be particularly suitable for the characteristics that child, old people, bed patient and dysphagia patients are taken, but also has working condition and production equipment is simple, production cost is low, compares the advantage that supplementary product consumption reduces with capsule, has demonstrated fully the new drug research exploitation spirit that people-oriented.
For achieving the above object, the present invention by the following technical solutions: the VENLAFAXINE HCL fine powder of 1 weight portion through micronizing is added in 1～10 weight portion molten matrix, fully mixing, dropping preparation method is condensed into ball in coolant, remove coolant, drying, promptly.
The chemical name of VENLAFAXINE HCL is (±)-1-[2-(dimethylamino)-1-(4-anisyl) ethyl among the present invention] the Hexalin hydrochlorate, molecular formula is C
17H
27NO
2Hcl, molecular weight are 313.87, and structural formula is
Substrate among the present invention includes but not limited to polyethylene glycol 6000, Macrogol 4000, polyethylene glycol 1500, cetomacrogol 1000, sodium stearate, glycerin gelatine, poloxamer, stearic acid, glycerol monostearate acid, insect wax etc.
Coolant among the present invention includes but not limited to dimethicone, liquid paraffin, vegetable oil, water, alcoholic solution etc.
Below through detecting to beneficial effect of the present invention as directed
One, detects index and method
1. disintegrate (molten loosing) time limit: check according to inspection technique disintegration (two appendix XA of Chinese Pharmacopoeia version in 2000).
2. dissolution rate: sample thief according to dissolution method (two appendix XC first methods of Chinese Pharmacopoeia version in 2000), is a solvent with water 900ml, and rotating speed is that per minute 75 changes, operation in accordance with the law.In the time of 10,20,30,40 minutes, get solution 5ml, filter, subsequent filtrate is as need testing solution.Other is taken at 105 ℃ of about 11mg of VENLAFAXINE HCL reference substance that are dried to constant weight, accurate claims surely, puts in the 100ml measuring bottle, is dissolved in water and is diluted to scale, shakes up, and it is an amount of that precision is measured this solution, and dilute with water is made reference substance solution.According to spectrophotography (two appendix IVA of Chinese Pharmacopoeia version in 2000), measure trap at the wavelength place of 225nm, calculate stripping quantity.
Two, commercially available VENLAFAXINE HCL capsule testing result
1. disintegration time: 54 minutes
2. dissolution rate:
Time (minute) 10 20 30 40
Dissolution (%) 25.3 48.9 71.2 83.6
Three, example 1 sample detection result
1. the molten diffusing time: 3 minutes
2. dissolution rate:
Time (minute) 10 20 30 40
Dissolution (%) 58.4 92.3 99.7 101.4
Four, example 2 sample detection results
1. the molten diffusing time: 3 minutes
2. dissolution rate:
Time (minute) 10 20 30 40
Dissolution (%) 61.4 96.8 99.3 98.2
Five, example 3 sample detection results
1. the molten diffusing time: 3 minutes
2. dissolution rate:
Time (minute) 10 20 30 40
Dissolution (%) 51.4 92.3 98.4 99.1
Six, example 4 sample detection results
1. the molten diffusing time: 4 minutes
2. dissolution rate:
Time (minute) 10 20 30 40
Dissolution (%) 41.4 86.9 98.7 100.3
Seven, example 5 sample detection results
1. the molten diffusing time: 7 minutes
2. dissolution rate:
Time (minute) 10 20 30 40
Dissolution (%) 42.4 89.5 98.6 97.2
Eight, example 6 sample detection results
1. the molten diffusing time: 6 minutes
2. dissolution rate
Time (minute) 10 20 30 40
Dissolution (%) 45.6 86.7 95.3 96.2
The specific embodiment
One, example 1
Prescription:
VENLAFAXINE HCL 5g
Polyethylene glycol 6000 15g
Make 1000
Method for making: the VENLAFAXINE HCL fine powder that the micronizing of learning from else's experience is crossed 200 mesh sieves is added in the fused polyethylene glycol 6000 substrate, stirs evenly, and with the dimethicone coolant, the dropping preparation method pill, drying, promptly.
Two, example 2
Prescription:
VENLAFAXINE HCL 5g
Macrogol 4000 15g
Make 1000
Method for making: the VENLAFAXINE HCL fine powder that the micronizing of learning from else's experience is crossed 200 mesh sieves is added in the fused Macrogol 4000 substrate, stirs evenly, and with the dimethicone coolant, the dropping preparation method pill, drying, promptly.
Three, example 3
Prescription:
VENLAFAXINE HCL 5g
Polyethylene glycol 6000 10g
Macrogol 4000 5g
Make 1000
Method for making: the VENLAFAXINE HCL fine powder that the micronizing of learning from else's experience is crossed 200 mesh sieves is added in fused Macrogol 4000 and the polyethylene glycol 6000 mixed-matrix, stirs evenly, and with the dimethicone coolant, the dropping preparation method pill, drying, promptly.
Four, example 4
Prescription:
VENLAFAXINE HCL 5g
Glyceryl monostearate 15g
Make 1000
Method for making: the VENLAFAXINE HCL fine powder that the micronizing of learning from else's experience is crossed 200 mesh sieves is added in the fused glyceryl monostearate substrate, and mixing is a coolant with the frozen water, the dropping preparation method pill, and drying, promptly.
Five, example 5
Prescription:
VENLAFAXINE HCL 5g
Polyethylene glycol 6000 10g
Poloxamer 5g
Make 1000
Method for making: the VENLAFAXINE HCL fine powder that the micronizing of learning from else's experience is crossed 200 mesh sieves is added in fused polyethylene glycol 6000 and the poloxamer mixed-matrix, stirs evenly, and with the dimethicone coolant, the dropping preparation method pill, drying, promptly.
Six, example 6
Prescription:
VENLAFAXINE HCL 5g
Glyceryl monostearate 15g
Poloxamer 1g
Make 1000
Method for making: get the mixing fine powders that VENLAFAXINE HCL and poloxamer cross 200 mesh sieves through micronizing and be added in the fused glyceryl monostearate substrate, mixing is a coolant with the frozen water, the dropping preparation method pill, and drying, promptly.
Claims (4)
1. VENLAFAXINE HCL drop pill and preparation method thereof is characterized in that: the VENLAFAXINE HCL fine powder of 1 weight portion through micronizing is added in 1～10 weight portion molten matrix, fully mixing, dropping preparation method is condensed into ball in coolant, remove coolant, drying, promptly.
2. the chemical name of the described VENLAFAXINE HCL of claim 1 is (±)-1-[2-(dimethylamino)-1-(4-anisyl) ethyl] the Hexalin hydrochlorate, molecular formula is C
17H
27NO
2Hcl, molecular weight are 313.87, and structural formula is
3. the described substrate of claim 1 includes but not limited to polyethylene glycol 6000, Macrogol 4000, polyethylene glycol 1500, cetomacrogol 1000, sodium stearate, glycerin gelatine, poloxamer, stearic acid, glycerol monostearate acid, insect wax etc.
4. the described coolant of claim 1 includes but not limited to dimethicone, liquid paraffin, vegetable oil, water, alcoholic solution etc.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410044438 CN1568948A (en) | 2004-05-13 | 2004-05-13 | Venlafaxine hydrochloride drop pills and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410044438 CN1568948A (en) | 2004-05-13 | 2004-05-13 | Venlafaxine hydrochloride drop pills and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1568948A true CN1568948A (en) | 2005-01-26 |
Family
ID=34481888
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200410044438 Pending CN1568948A (en) | 2004-05-13 | 2004-05-13 | Venlafaxine hydrochloride drop pills and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1568948A (en) |
-
2004
- 2004-05-13 CN CN 200410044438 patent/CN1568948A/en active Pending
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |