CN1546037A - Diazepam dripping pills and its preparation process - Google Patents

Abstract

The invention relates to a Diazepam drop pill prepared by utilizing ultramicro disintegration and drop pill manufacturing process, 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

Diazepam drop pill and preparation method thereof

Technical field

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

Background technology

Diazepam is the Benzodiazepines antianxiety drugs, has anxiety, calmness, hypnosis, convulsion, epilepsy and central myorelaxant effects.Its angst resistance effect selectivity is very strong, is 5 times of chlordiazepoxide, and this may optionally act on the cerebral limbic system with it, promotes the release of r-aminobutyric acid (GA-BA) or promotes that the synapse propagation function is relevant with the combination of maincenter benzodiazepine receptors.But sleep inducing when heavy dose of, compare with the barbiturates hypnotic, it have the therapeutic index height, to breathe influence little, to several nothings influences of fast wave sleep (REM), liver drug enzyme is not had influence, does not also cause characteristics such as anesthesia when heavy dose of, be present the most frequently used clinically hypnotic.Have antiepileptic action preferably in addition, extremely effective to status epilepticus, can make 70%～80% epilepsy controlled during intravenous injection, but petit mal epilepsy and children's's clonicity are taken place not as nitrazepam.The effect of central muscular flaccidity is stronger than chlordiazepoxide, be its 5 times, and anticonvulsant action is very strong, is 10 times of chlordiazepoxide.Oral absorption is fast, reaches the blood peak concentration in about 1 hour, and the intramuscular injection post-absorption is irregular, and intravenous injection enters maincenter rapidly and comes into force and slow, but distributes fast again, so the persistent period is short.Blood plasma t _1/2Be 20～50 hours, belong to long-acting medicine.Through liver metabolism is oxazepam, still has biological activity, so continuous application can be accumulated.Can see through placental barrier enters in the fetus body.Mainly discharge, also can drain from milk from kidney.

Clinical practice is in treatment: 1. anxiety neurosis and various neurosis.2. insomnia: splendid to anxiety aypnia curative effect especially.3. epilepsy: can share with other antuepileptic, treatment epilepsy grand mal or petit mal are answered intravenous injection during the Taking Control of Epilepsy persistent state.4. the convulsions that causes of a variety of causes: as eclamposia, tetanus, children's's hyperpyrexia convulsions etc.5. muscle spasm due to cerebrovascular accident or spinal cord injury sexual centre myotonia or lumbar muscle strain, the endoscopy etc.

The diazepam odorless, mildly bitter flavor, almost insoluble in water, its disintegration of tablet time is long, and dissolution and dissolution rate are low, absorption difference, bioavailability is low, and the supplementary product consumption ratio is big, and child, old people, bed patient and dysphagia patients are taken inconvenience, compliance is poor, has influenced the performance of diazepam therapeutical effect.

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

Summary of the invention

The diazepam 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 tablet, 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 diazepam 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 diazepam is 1-methyl-5-phenyl-7-chloro-1 among the present invention, 3-dihydro-2H-1, and 4-benzodiazepine-2-ketone, structural formula is Molecular formula is C ₁₆H ₁₃CLN ₂O, molecular weight are 284.74.

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), 800ml is a solvent with hydrochloric acid solution (9 → 1000), and rotating speed is that per minute 100 changes, operation in accordance with the law, in the time of 10,20,30,40 minutes, get the about 10ml of solution, filter, filtrate is immediately according to spectrophotography (two appendix IVA of Chinese Pharmacopoeia version in 2000), wavelength place at 242nm ± 2nm measures trap, presses C ₁₆H ₁₃CLN ₂Absorptance (the E of O _1cm ^1%) be 1018 calculating stripping quantities.

Two, commercially available diazepam tablets testing result

1. disintegration time: 60 minutes

2. dissolution rate:

Time (minute) 10 20 30 40

Dissolution (%) 21.3 35.4 68.9 80.2

Three, example 1 sample detection result

1. the molten diffusing time: 3 minutes

2. dissolution rate:

Time (minute) 10 20 30 40

Dissolution (%) 45.4 79.6 92.3 98.7

Four, example 2 sample detection results

1. the molten diffusing time: 3 minutes

2. dissolution rate:

Time (minute) 10 20 30 40

Dissolution (%) 50.4 82.5 93.7 99.0

Five, example 3 sample detection results

1. the molten diffusing time: 3 minutes

2. dissolution rate:

Time (minute) 10 20 30 40

Dissolution (%) 43.5 78.3 90.4 96.7

Six, example 4 sample detection results

1. the molten diffusing time: 5 minutes

2. dissolution rate:

Time (minute) 10 20 30 40

Dissolution (%) 39.2 72.4 86.5 98.9

Seven, example 5 sample detection results

1. the molten diffusing time: 8 minutes

2. dissolution rate:

Time (minute) 10 20 30 40

Dissolution (%) 36.7 65.7 92.3 96.5

Eight, example 6 sample detection results

1. the molten diffusing time: 8 minutes

2. dissolution rate

Time (minute) 10 20 30 40

Dissolution (%) 40.3 76.4 92.7 100.6

The specific embodiment

One, example 1

Prescription:

Diazepam 5g

Polyethylene glycol 6000 15g

Make 1000

Method for making: the diazepam 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:

Diazepam 5g

Macrogol 4000 15g

Make 1000

Method for making: the diazepam 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:

Diazepam 5g

Polyethylene glycol 6000 5g

Macrogol 4000 10g

Make 1000

Method for making: the diazepam 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:

Diazepam 5g

Glyceryl monostearate 15g

Make 1000

Method for making: the diazepam 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:

Diazepam 5g

Polyethylene glycol 6000 10g

Poloxamer 5g

Make 1000

Method for making: the diazepam 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:

Diazepam 5g

Glyceryl monostearate 15g

Poloxamer 1g

Make 1000

Method for making: get the mixing fine powders that diazepam 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. diazepam drop pill and preparation method thereof is characterized in that: the diazepam 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 diazepam of claim 1 is 1-methyl-5-phenyl-7-chloro-1,3-dihydro-2H-1, and 4-benzodiazepine-2-ketone, molecular formula is C ₁₆H ₁₃CLN ₂O, molecular weight are 284.74, 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.