CN102525981A - Propranolol hydrochloride tablets and preparation method thereof - Google Patents

Abstract

The invention relates to a preparation method for propranolol hydrochloride tablets. The method comprises the following steps of: 1) preparing a carrier for solid dispersoid, namely weighing 200 grams of polyethylene glycol (PEG) 6000, dissolving the PEG 6000 in 95 percent (ml/ml) ethanol to obtain an auxiliary material solution, dissolving 100 grams of propranolol hydrochloride in 95 percent (ml/ml) ethanol to obtain a main medicine solution, mixing the auxiliary material solution and the main medicine solution uniformly to obtain a mixed solution, and drying the mixed solution at temperature of between 35 and 55 DEG C under the vacuum with the vacuum degree of less than 10 Pa for 12 to 24 hours; 2) preparing tablets, namely crushing the materials obtained in the step 1), and sieving to obtain solid dispersoid powder; adding a formula dose of dextrin into the solid dispersoid powder, and putting the mixture into a granulator, performing dry mixing for 5 to 10 minutes, adding 40 to 50 percent ethanol serving as an adhesive, and granulating; sieving the materials with a 20-to-30-mesh sieve, granulating in the wet state, and transferring to a fluidized drying machine for drying until the moisture is 5 to 8 percent; and sieving the dried granules with a 20-to-30-mesh sieve, granulating, and mixing the obtained granules and a lubricating agent in a formula uniformly for tabletting.

Description

A kind of propranolol hydrochloride sheet and preparation method thereof

Technical field

The invention belongs to technical field of medicine, be specifically related to a kind of propranolol hydrochloride piece preparation method.

Background technology

Propranolol hydrochloride is a beta-receptor blockader, the beta receptor of blocking-up cardiac muscle, and decreased heart rate suppresses cardiac contractile force and conduction, circulation volume minimizing, myocardial oxygen consumption reduction.The clinical arrhythmia of treatment due to the multiple reason that be mainly used in also can be used for angina pectoris hypertension pheochromocytoma (preparing before the operation) etc.

Though measuring according to the method for Chinese Pharmacopoeia appendix XE, the uniformity of dosage units of common propranolol hydrochloride sheet meets the pharmacopeia regulation; But the absolute value A of the labelled amount of stipulating among the appendix XE and the difference of average is often bigger; A+1.80S approaches 15, explains that the uniformity of dosage units of common propranolol hydrochloride tablet is not very good.Influence the homogeneity of product.

Measure dissolution according to the method for Chinese Pharmacopoeia appendix XC first method, common propranolol hydrochloride sheet stripping quantity though meet the regulation of pharmacopeia " limit be labelled amount 75% ", but still can further improve dissolution generally about 80%.

Summary of the invention

The present invention will solve common propranolol hydrochloride sheet uniformity of dosage units and all unfavorable technical problem of dissolution; Adopt PEG6000 as preparing carriers propranolol hydrochloride solid dispersion; Then be prepared into the agent of solid dispersion matrix; Gained propranolol hydrochloride tablet content good evenness, dissolution can arrive more than 90% of labelled amount, improve drug bioavailability, ensure drug quality.

A kind of propranolol hydrochloride sheet, write out a prescription as follows:

The supplementary material title	Per 10,000 consumptions
		Propranolol hydrochloride	?100g
Dextrin	?430g
		PEG6000	?200g
95% (ml/ml) ethanol	?600-800ml
		40～50% (ml/ml) ethanol	In right amount
Lubricant	?7.5g

Said lubricant is selected from magnesium stearate, micropowder silica gel or Pulvis Talci.

A kind of method for preparing of propranolol hydrochloride sheet:

1), the preparation of solid dispersion carrier: take by weighing PEG6000200g and add 300-400ml 95% (ml/ml) ethanol and dissolve fully to PEG6000, adjuvant solution; The 100g propranolol hydrochloride is dissolved in 300-400ml 95% (ml/ml) ethanol winner drug solns; Adjuvant solution and principal agent solution mix homogeneously are got mixed solution; With mixed solution vacuum drying 12-24 hour, vacuum was less than 10Pa, and temperature 35-55 ℃, the control moisture is less than 1%;

2), preparation tablets: the 100-120 mesh standard sieve is pulverized, crossed to step 1) gained material get the solid dispersion powder; Gained solid dispersion powder, dextrin 430g are put into granulator, do and mix 5-10min, ethanol is moistening in right amount to add 40～50% (ml/ml), and setting the shears frequency is 20-30Hz, shear granulation 5-10min; Material is crossed and is moved to boiling drier behind the wet granulate of 20-30 mesh sieve and be dried to moisture 5-8%; Dried granule is crossed 20-30 mesh sieve granulate, and with the mix lubricant 5-10min in granule that obtains and the prescription, tabletting gets 10,000.

Technique effect of the present invention:

1, gained propranolol hydrochloride sheet adopts PEG6000 as the solid dispersion carrier, and main component is distributed in the carrier with molecularity, and uniformity of dosage units is greatly improved, and guarantees the product homogeneity; Owing to select the dextrin filler for use, dextrin has adsorption to principal agent, process solid dispersion after, can eliminate dextrin to the effect of crude drug Molecular Adsorption, improve the stripping of medicine.

2, process the slice, thin piece that makes again behind the solid dispersion, quality homogeneous between criticizing between sheet and the sheet and criticizing.Dissolution rate is fast, helps to improve bioavailability of drugs.

3, unilateral smooth, the brighter and cleaner brilliant white of tablet than traditional handicraft makes increases patient compliance.

4, compressibility is good, only needs less pressure just can extrude hardness and friability and meets the tablet that pharmacopeia requires.

Description of drawings

The propranolol hydrochloride sheet of Fig. 1 applying solid dispersion technology preparation of the present invention and the propranolol hydrochloride sheet dissolution rate of common process preparation are relatively;

The propranolol hydrochloride sheet of

expression common process preparation among the figure, the propranolol hydrochloride sheet of

expression applying solid dispersion technology preparation.

The specific embodiment

Embodiment 1 propranolol hydrochloride piece preparation method

1), the preparation of solid dispersion carrier: take by weighing PEG6000 200g and add 300mL95% (ml/ml) ethanol and dissolve fully to PEG6000, adjuvant solution; The 100g propranolol hydrochloride is dissolved in 300ml 95% (ml/ml) ethanol winner drug solns; Adjuvant solution and principal agent solution mix homogeneously are got mixed solution; With mixed solution vacuum drying 12 hours, vacuum was less than 10Pa, 35 ℃ of temperature, and the control moisture is less than 1%;

2), preparation tablets: 100 mesh standard sieves are pulverized, crossed to step 1) gained material get the solid dispersion powder; Gained solid dispersion powder, dextrin 430g are put into granulator, do and mix 5min, adding 40% an amount of ethanol is moistening, and setting the shears frequency is 20Hz, shear granulation 5min; Material is crossed and is moved to boiling drier behind the wet granulate of 20 mesh sieves to be dried to moisture be 5%; Dried granule is crossed 20 mesh sieve granulate, and with the mix lubricant 5min in granule that obtains and the prescription, tabletting gets 10,000.Compressibility is good, only needs less pressure just can extrude hardness and friability and meets the tablet (seeing the following form 1) that pharmacopeia requires.

Table 1 compression force and hardness and friability relation

Compression force (KN)	Hardness (Kg)	Friability
			4.1	5.5	0.5％
6.3	8.7	0.4％
			9.8	12.2	0.1％

Embodiment 2 propranolol hydrochloride piece preparation methods

1), the preparation of solid dispersion carrier: take by weighing PEG6000200g and add 400ml 95% (ml/ml) ethanol and dissolve fully to PEG6000, adjuvant solution; The 100g propranolol hydrochloride is dissolved in 400ml 95% (ml/ml) ethanol winner drug solns; Adjuvant solution and principal agent solution mix homogeneously are got mixed solution; With mixed solution vacuum drying 24 hours, vacuum was less than 10Pa, 55 ℃ of temperature, and the control moisture is less than 1%;

2), preparation tablets: 120 mesh standard sieves are pulverized, crossed to step 1) gained material get the solid dispersion powder; Gained solid dispersion powder, dextrin 430g are put into granulator, do to mix 10min, it is moistening to add an amount of 50% ethanol, and setting the shears frequency is 30Hz, shear granulation 10min; Material is crossed and is moved to boiling drier behind the wet granulate of 30 mesh sieves and be dried to moisture 8%; Dried granule is crossed 30 mesh sieve granulate, and with the mix lubricant 10min in granule that obtains and the prescription, tabletting gets 10,000.Compressibility is good, only needs less pressure just can extrude hardness and friability and meets the tablet (seeing the following form 2) that pharmacopeia requires.

Table 2 compression force and hardness and friability relation

The inspection of embodiment 3 tablet qualities

1, outward appearance

Unilateral bright and clean, the Bai Liang of embodiment 1,2 gained propranolol hydrochloride sheets.

2, uniformity of dosage units

Embodiment 1,2 gained propranolol hydrochloride sheets are respectively got 10, according to 2010 editions two appendix XE inspections of Chinese Pharmacopoeia uniformity of dosage units.Measuring every is 100 relative amount with labelled amount, the average of getting 10 relative amounts.Embodiment 1, routine 2:A+1.84S are less than 5, and the uniformity of dosage units of gained propranolol hydrochloride sheet is good.

3, dissolution

Embodiment 1,2 gained propranolol hydrochloride sheets are respectively got 6, and according to 2010 editions two appendix XC inspections of Chinese Pharmacopoeia dissolution, the stripping quantity that embodiment is 1,2 calculates all more than 90% according to labelled amount.(seeing accompanying drawing 1)

With above-mentioned foundation desirable embodiment of the present invention is enlightenment, and through above-mentioned description, the related work personnel can carry out various change and modification fully in the scope that does not depart from this invention technological thought.The technical scope of this invention is not limited to the content on the description, must confirm its technical scope according to the claim scope.

Claims (2)

1. propranolol hydrochloride sheet, prescription be as follows:

The supplementary material title Per 10,000 consumptions Propranolol hydrochloride ?100g Dextrin ?430g PEG6000 ?200g 95% (ml/ml) ethanol ?600-800ml 40～50% (ml/ml) ethanol In right amount Lubricant ?7.5g

2. the method for preparing of the said propranolol hydrochloride sheet of claim 1:

1), the preparation of solid dispersion carrier: take by weighing PEG6000 200g and add 400ml 95% (ml/ml) ethanol and dissolve fully to PEG6000, adjuvant solution; The 100g propranolol hydrochloride is dissolved in 200ml 95% (ml/ml) ethanol winner drug solns; Adjuvant solution and principal agent solution mix homogeneously are got mixed solution; With mixed solution vacuum drying 12-24 hour, vacuum was less than 10Pa, and temperature 35-55 ℃, the control moisture is less than 1%.

2), preparation tablets: the 100-120 mesh standard sieve is pulverized, crossed to step 1) gained material get the solid dispersion powder; Gained solid dispersion powder, dextrin 430g are put into granulator, do and mix 5-10min, ethanol is moistening in right amount to add 40～50% (ml/ml), and setting the shears frequency is 20-30Hz, shear granulation 5-10min; Material is crossed and is moved to boiling drier behind the wet granulate of 20-30 mesh sieve and be dried to moisture 5-8%; Dried granule is crossed 20-30 mesh sieve granulate, and with the mix lubricant 5-10min in granule that obtains and the prescription, tabletting gets 10,000.

Images