CN1568947A - Bromhexine Hydrochloride drop pills and preparation method thereof - Google Patents

Abstract

The invention discloses a bromhexine 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, oral or swallow administration, it has good compliance, thus is especially suitable for children, the elderly, bedridden patients and dysphagia patients.

Description

Bromhexine hydrochloride drop pill and preparation method thereof

Technical field

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

Background technology

Bromhexine hydrochloride has stronger dissolving to glue the expectorant effect, can make the plain cracking of polysaccharide fiber of apoplexy due to phlegm, and the desaturation sputum suppresses the synthetic glycoprotein of goblet cell and mucus body of gland sputum acid is reduced, and lowers expectorant viscosity, is convenient to discharge.

Bromhexine hydrochloride is fast and complete from gastrointestinal absorption, 1 hour blood drug level peaking after the oral absorption.The metabolite of the overwhelming majority is discharged with urine, and feces is only discharged minimum part.The oral formulations of list marketing at present only has tablet, clinically is used for the treatment of as expectorant that expectorant such as chronic bronchitis, asthma are sticking to be difficult for expectoration and to cause patient out of breath.

The bromhexine hydrochloride odorless, tasteless, soluble,very slightly 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 bromhexine hydrochloride therapeutical effect.

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

Summary of the invention

The bromhexine hydrochloride 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 bromhexine hydrochloride 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 bromhexine hydrochloride is N-methyl-N-cyclohexyl-2-amino-3.5-dibromobenzene methylamine hydrochloride among the present invention, and structural formula is, HCl, molecular formula is C ₁₄H ₂₀Br ₂N ₂.Hcl, molecular weight is 412.60.

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), 900ml 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 solution 10ml, filter, get subsequent filtrate, according to spectrophotography (two appendix IVA of Chinese Pharmacopoeia version in 2000), measure trap at the wavelength place of 249nm, press C ₁₄H ₂₀Br ₂N ₂Absorptance (the E of Hcl _1cm ^1%) be 270 calculating stripping quantities.

Two, commercially available bromhexine hydrochloride sheet testing result

1. disintegration time: 63 minutes

2. dissolution rate:

Time (minute) 10 20 30 40

Dissolution (%) 21.4 38.7 53.2 76.5

Three, example 1 sample detection result

1. the molten diffusing time: 2 minutes

2. dissolution rate:

Time (minute) 10 20 30 40

Dissolution (%) 55.7 86.4 99.8 98.9

Four, example 2 sample detection results

1. the molten diffusing time: 3 minutes

2. dissolution rate:

Time (minute) 10 20 30 40

Dissolution (%) 51.2 89.5 96.7 98.3

Five, example 3 sample detection results

1. the molten diffusing time: 3 minutes

2. dissolution rate:

Time (minute) 10 20 30 40

Dissolution (%) 49.4 87.5 98.6 100.3

Six, example 4 sample detection results

1. the molten diffusing time: 4 minutes

2. dissolution rate:

Time (minute) 10 20 30 40

Dissolution (%) 39.8 79.6 95.3 98.7

Seven, example 5 sample detection results

1. the molten diffusing time: 5 minutes

2. dissolution rate:

Time (minute) 10 20 30 40

Dissolution (%) 43.5 81.4 93.2 96.0

Eight, example 6 sample detection results

1. the molten diffusing time: 6 minutes

2. dissolution rate

Time (minute) 10 20 30 40

Dissolution (%) 43.3 86.5 95.4 98.7

The specific embodiment

One, example 1

Prescription:

Bromhexine hydrochloride 8g

Polyethylene glycol 6000 12g

Make 1000

Method for making: the bromhexine hydrochloride 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:

Bromhexine hydrochloride 8g

Macrogol 4000 12g

Make 1000

Method for making: the bromhexine hydrochloride 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:

Bromhexine hydrochloride 8g

Polyethylene glycol 6000 10g

Macrogol 4000 4g

Make 1000

Method for making: the bromhexine hydrochloride 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:

Bromhexine hydrochloride 8g

Glyceryl monostearate 15g

Make 1000

Method for making: the bromhexine hydrochloride 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:

Bromhexine hydrochloride 8g

Polyethylene glycol 6000 10g

Poloxamer 3g

Make 1000

Method for making: the bromhexine hydrochloride 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:

Bromhexine hydrochloride 8g

Glyceryl monostearate 15g

Poloxamer 2g

Make 1000

Method for making: get the mixing fine powders that bromhexine hydrochloride 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. bromhexine hydrochloride drop pill and preparation method thereof is characterized in that: the bromhexine hydrochloride 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 bromhexine hydrochloride of claim 1 is N-first-N-cyclohexyl-2-amino-3.5-dibromobenzene methylamine hydrochloride, and structural formula is Molecular formula is C ₁₄H ₂₀Br ₂N ₂Hcl, molecular weight are 412.60.

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.