CN1602849A - Propranolol hydrochloride drop pills and its preparation method - Google Patents

Abstract

The invention uses super micro shattering and propranolol drop pills producing the technology to produce fenfluramine drop pills, reaching the purposes such as increasing speed, and dissolution of disintegration, increasing the medicine stability, reducing the dose of auxiliary materials and decreasing cost, with rapid effect and convenient use. It can be buccal as well as deglutition, has remarkable conformity, and is especially suitable for children, older man, sicker in bed or with difficulty of swallowing.

Description

Propranolol hydrochloride drop pill and preparation method thereof

Technical field

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

Background technology

Propranolol hydrochloride is that non-selective competition suppresses the epinephrine beta-blocker, the β on the blocking-up heart ₁, β ₂Receptor, antagonism sympathetic activation and catecholamine effect, the contractility and the contraction speed of reduction heart, suppressing vascular smooth muscle simultaneously shrinks, reduce myocardial oxygen consumption, the oxygen relation between supply and demand of ischemic myocardium is restored balance on low-level, can be used for treating angina pectoris.

Propranolol hydrochloride can suppress the adrenergic excitement of heartpacer current potential, is used for the treatment of arrhythmia, also can pass through maincenter, adrenergic neuron blockade, suppresses effects such as feritin release and heart output reduction, is used for the treatment of hypertension.

But the effect of propranolol hydrochloride competitive antagonism isoproterenol and norepinephrine, blocking-up β ₂Receptor reduces plasma renin activity.Can cause bronchospasm.Suppress insulin secretion, make blood sugar increasing, cover the hypoglycemia symptom, postpone hypoglycemic recovery.

Propranolol hydrochloride has tangible antiplatelet aggregative activity, with its membrane stabilizing action and inhibition platelet membrane Ca ²⁺Transport relevant.

The oral back of propranolol hydrochloride gastrointestinal absorption is more complete, and widely at intrahepatic metabolism, bioavailability is about 30%, reaches the blood drug level peak value in 1～1.5 hour after the administration, and eliminating the half-life is 2～3 hours, and plasma protein binding rate is 90%～95%.There is notable difference in individual blood drug level, and apparent volume of distribution is 3.9 ± 6L/kg.Through renal excretion, be mainly metabolite, fraction (＜1%) is female medicine.Can not discharge through dialysis.

The oral formulations of list marketing at present is a tablet, clinical in secondary prevention, reduce the myocardial infarction mortality rate, share treatment hypertension, treatment exertional angina pectoris separately or with other antihypertensive, control supraventricular tachy-arrhythmia, ventricular arrhythmia, particularly relevant or arrhythmia that Folium Digitalis Purpureae causes with catecholamine.The room that can be used for the Folium Digitalis Purpureae unsatisfactory curative effect is pounced on, the control of atrial fibrillation Ventricular Rate, also can be used for the intractable premature beat, improve patient's symptom, lower hypertrophic cardiomyopathy efferent tract pressure reduction, alleviate symptoms such as angina pectoris, cardiopalmus and faintness, cooperate the α receptor blocking agent to be used for the pheochromocytoma patient and control tachycardia, be used to control the rapid heart rate of hyperthyroidism, also can be used for treating thyroid storm.

Propranolol hydrochloride is distinguished the flavor of little sweet back bitter, in water, dissolve, but 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 propranolol hydrochloride therapeutical effect.

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

Summary of the invention

The propranolol 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, 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 propranolol 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.

The chemical name of propranolol hydrochloride is 1-isopropylamino-3-(1-naphthoxy)-2-propylate hydrochlorate among the present invention, and structural formula is

Molecular formula is C ₁₆H ₂₁NO ₂Hcl, molecular weight are 295.81.

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), 1000ml is a solvent with hydrochloric acid (1 → 100), 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 IV of Chinese Pharmacopoeia version in 2000 A), measure trap at the wavelength place of 290nm, press C ₁₆H ₂₁NO ₂Absorptance (the E of HCl _1cm ^1%) be 207 calculating stripping quantities.

Two, commercially available propranolol hydrochloride sheet testing result

1. disintegration time: 32 minutes

2. dissolution rate:

Time (minute) 10 20 30 40

Dissolution (%) 49.5 83.6 95.3 96.4

Three, example 1 sample detection result

1. the molten diffusing time: 2 minutes

2. dissolution rate:

Time (minute) 10 20 30 40

Dissolution (%) 68.7 98.9 99.2 99.0

Four, example 2 sample detection results

1. the molten diffusing time: 2 minutes

2. dissolution rate:

Time (minute) 10 20 30 40

Dissolution (%) 73.4 98.6 97.3 98.4

Five, example 3 sample detection results

1. the molten diffusing time: 2 minutes

2. dissolution rate:

Time (minute) 10 20 30 40

Dissolution (%) 62.3 99.7 100.0 100.7

Six, example 4 sample detection results

1. the molten diffusing time: 3 minutes

2. dissolution rate:

Time (minute) 10 20 30 40

Dissolution (%) 78.4 100.5 98.6 99.7

Seven, example 5 sample detection results

1. the molten diffusing time: 4 minutes

2. dissolution rate:

Time (minute) 10 20 30 40

Dissolution (%) 63.4 96.5 99.8 99.2

Eight, example 6 sample detection results

1. the molten diffusing time: 5 minutes

2. dissolution rate

Time (minute) 10 20 30 40

Dissolution (%) 67.8 98.2 99.0 97.3

The specific embodiment

One, example 1

Prescription:

Propranolol hydrochloride 5g

Polyethylene glycol 6000 15g

Make 1000

Method for making: the propranolol 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:

Propranolol hydrochloride 5g

Macrogol 4000 15g

Make 1000

Method for making: the propranolol 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:

Propranolol hydrochloride 5g

Polyethylene glycol 6000 5g

Macrogol 4000 10g

Make 1000

Method for making: the propranolol 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:

Propranolol hydrochloride 5g

Glyceryl monostearate 15g

Make 1000

Method for making: the propranolol 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:

Propranolol hydrochloride 5g

Polyethylene glycol 6000 10g

Poloxamer 5g

Make 1000

Method for making: the propranolol 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:

Propranolol hydrochloride 5g

Glyceryl monostearate 15g

Poloxamer 1g

Make 1000

Method for making: get the mixing fine powders that propranolol 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. propranolol hydrochloride drop pill and preparation method thereof is characterized in that: the propranolol 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 propranolol hydrochloride of claim 1 is 1-isopropylamino-3-(1-naphthoxy)-2-propylate hydrochlorate, and structural formula is , molecular formula is C ₁₆H ₂₁NO ₂Hcl, molecular weight are 295.81.

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.