CN1543961A - Oxazepam dripping pills and preparation thereof - Google Patents

Abstract

The invention discloses an Oxazepam drop pill prepared through ultramicro disintegration and drop pills manufacturing technique, which has the advantages of improving collapse and dissolving speed, high dissolving rate, quick effect, increased medicament stability, oral or swallow administration, and good compliance.

Description

Oxazepam drop pill and preparation method thereof

Technical field

The present invention relates to a kind of pharmaceutical product and preparation method thereof, specifically oxazepam drop pill and preparation method thereof.

Background technology

Oxazepam is the activity in vivo metabolite of chlordiazepoxide, diazepam.Structure is similar to chlordiazepoxide and diazepam with pharmacological action.

The oral post-absorption of oxazepam is slower.The protein binding rate height, through liver metabolism, the non-activity metabolite.T _1/2Be generally 5～12 hours, genus is as short as medium drug effect.The effect beginning in 45～90 minutes of oral back, 2～4 hours blood drug level peakings, a couple of days blood drug level reach stable state.Through renal excretion, the body accumulation amount is minimum.List marketing at present tablet only arranged, clinically be mainly used in anxiety, anxiety, excitement, also can be used for hypnosis, anxiety with dysthymic adjuvant drug, and can alleviate the acute alcohol withdrawal symptom.

Oxazepam is odorless almost, almost insoluble in water, its disintegration of tablet 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 oxazepam therapeutical effect.

The present invention makes the oxazepam drop pill by using ultramicro communication technique and dropping pill formulation Technology exactly, thereby overcomes the above defective of oxazepam sheet, and the therapeutical effect of oxazepam is given full play to.

Summary of the invention

The oxazepam 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, both can swallow also can buccal, 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 have working condition and production equipment is simple, production cost is low, compare the advantage that supplementary product consumption reduces with tablet, 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 oxazepam fine powder of 1 weight portion through micronizing is added in 1～10 weight portion molten matrix, abundant mixing, dropping preparation method is condensed into ball in coolant, remove coolant, drying, promptly.

The chemical name of oxazepam among the present invention (Oxazepam) is 5-phenyl-3-hydroxyl-7-chloro-1,3-dihydro-2H-1, and 4-benzodiazepine-2-ketone, molecular formula is C ₁₅H ₁₁ClN ₂O ₂, molecular weight is 286.72, 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 second methods of Chinese Pharmacopoeia version in 2000), 1000ml is a solvent with hydrochloric acid solution (9 → 1000), rotating speed is that per minute 50 changes, and operation in accordance with the law is in the time of 10,20,30,40 minutes, it is an amount of to get solution, filters; Other gets oxazepam reference substance 15mg, puts in the 100ml measuring bottle, adds ethanol 10ml and makes dissolving, is diluted to scale with hydrochloric acid solution (9 → 1000), shakes up, and precision is measured 5ml, puts in the 50ml measuring bottle, is diluted to scale with hydrochloric acid solution (9 → 1000), shakes up.Get above-mentioned two kinds of solution,, measure trap respectively, calculate stripping quantity at the wavelength place of 283nm according to spectrophotography (two appendix IV of Chinese Pharmacopoeia version in 2000 A).

Two, commercially available oxazepam sheet testing result

1. disintegration time: 64 minutes

2. dissolution rate:

Time (minute) 10 20 30 40

Dissolution (%) 18.9 31.2 41.5 53.6

Three, example 1 sample detection result

1. the molten diffusing time: 6 minutes

2. dissolution rate:

Time (minute) 10 20 30 40

Dissolution (%) 43.5 72.3 89.7 98.4

Four, example 2 sample detection results

1. the molten diffusing time: 4 minutes

2. dissolution rate:

Time (minute) 10 20 30 40

Dissolution (%) 46.6 78.9 92.4 99.6

Five, example 3 sample detection results

1. the molten diffusing time: 3 minutes

2. dissolution rate:

Time (minute) 10 20 30 40

Dissolution (%) 41.4 76.3 93.6 97.8

Six, example 4 sample detection results

1. the molten diffusing time: 7 minutes

2. dissolution rate:

Time (minute) 10 20 30 40

Dissolution (%) 38.9 68.4 85.2 93.6

Seven, example 5 sample detection results

1. the molten diffusing time: 6 minutes

2. dissolution rate:

Time (minute) 10 20 30 40

Dissolution (%) 42.7 78.4 85.3 94.6

Eight, example 6 sample detection results

1. the molten diffusing time: 10 minutes

2. dissolution rate

Time (minute) 10 20 30 40

Dissolution (%) 46.7 79.2 93.4 99.1

The specific embodiment

One, example 1

Prescription:

Oxazepam 5g

Polyethylene glycol 6000 15g

Make 1000

Method for making: the oxazepam 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:

Oxazepam 5g

Macrogol 4000 15g

Make 1000

Method for making: the oxazepam 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:

Oxazepam 5g

Polyethylene glycol 6000 5g

Macrogol 4000 10g

Make 1000

Method for making: the oxazepam 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:

Oxazepam 5g

Glyceryl monostearate 15g

Make 1000

Method for making: the oxazepam 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:

Oxazepam 5g

Polyethylene glycol 6000 10g

Poloxamer 5g

Make 1000

Method for making: the oxazepam 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:

Oxazepam 5g

Glyceryl monostearate 15g

Poloxamer 1g

Make 1000

Method for making: get the mixing fine powders that oxazepam 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. oxazepam drop pill and preparation method thereof is characterized in that: the oxazepam fine powder of 1 weight portion through micronizing is added in 1～10 weight portion molten matrix, and abundant mixing, dropping preparation method is condensed into ball in coolant, remove coolant, drying, promptly.

2. the chemical name of the described oxazepam Oxazepam of claim 1 is 5-phenyl-3-hydroxyl-7-chloro-1,3-dihydro-2H-1, and 4-benzodiazepine-2-ketone, molecular formula is C ₁₅H ₁₁ClN ₂O ₂, molecular weight is 286.72, 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.