CN1568948A - Venlafaxine hydrochloride drop pills and preparation method thereof - Google Patents

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

VENLAFAXINE HCL drop pill and preparation method thereof

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.