CN102525981B - 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 tablets and preparation method thereof

Technical field

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

Background technology

Propranolol hydrochloride is beta-receptor blockader, blocks myocardium beta receptor, and decreased heart rate suppresses cardiac contractile force and conduction, circulation volume minimizing, myocardial oxygen consumption reduction.The clinical arrhythmia that is mainly used in treating due to many reasons, also can be used for angina pectoris hypertension pheochromocytoma (pre-operative preparation) etc.

Although the uniformity of dosage units of common propranolol hydrochloride tablets is measured and is met pharmacopeia regulation according to the method for Chinese Pharmacopoeia appendix XE, but the absolute value A of the labelled amount stipulating in appendix XE and the difference of average is often larger, A+1.80S, close to 15, illustrates that the uniformity of dosage units of common propranolol hydrochloride tablet is not very good.Affect the homogeneity of product.

Measure dissolution according to the method for Chinese Pharmacopoeia appendix XC first method, common propranolol hydrochloride tablets stripping quantity is generally in 80% left and right, though meet the regulation of pharmacopeia " 75% that limit is labelled amount ", but still can further improve dissolution.

Summary of the invention

The present invention will solve all undesirable technical problems of common propranolol hydrochloride tablets uniformity of dosage units and dissolution, adopt PEG6000 to prepare propranolol hydrochloride solid dispersion as carrier, then be prepared into the agent of solid dispersion matrix, gained propranolol hydrochloride tablets agent content good evenness, dissolution can arrive the more than 90% of labelled amount, improve drug bioavailability, ensure drug quality.

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

Supplementary material title	Every 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

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

A kind of preparation method of propranolol hydrochloride tablets:

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

2), tablet preparation: by step 1) gained crushing material, cross 100-120 mesh standard sieve and obtain solid dispersion powder; Gained solid dispersion powder, dextrin 430g are put into granulator, be dry mixed 5-10min, add the appropriate ethanol of 40～50% (ml/ml) moistening, setting shears frequency is 20-30Hz, shear granulation 5-10min; Material is crossed and is moved to boiling drier after 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 by the mix lubricant 5-10min in the granule obtaining and prescription, tabletting, obtains 10,000.

Technique effect of the present invention:

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

2, make the slice, thin piece making again after solid dispersion, quality homogeneous between batches between sheet and sheet.Dissolution rate is fast, contributes to improve bioavailability of drugs.

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

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

Accompanying drawing explanation

Propranolol hydrochloride tablets dissolution rate comparison prepared by propranolol hydrochloride tablets prepared by Fig. 1 applying solid dispersion technology of the present invention and common process;

In figure

represent propranolol hydrochloride tablets prepared by common process,

represent propranolol hydrochloride tablets prepared by applying solid dispersion technology.

The specific embodiment

Embodiment 1 propranolol hydrochloride tablets preparation method

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

2), tablet preparation: by step 1) gained crushing material, cross 100 mesh standard sieves and obtain solid dispersion powder; Gained solid dispersion powder, dextrin 430g are put into granulator, be dry mixed 5min, add 40% appropriate ethanol moistening, setting shears frequency is 20Hz, shear granulation 5min; Material is crossed and is moved to boiling drier after the wet granulate of 20 mesh sieves to be dried to moisture be 5%; Dried granule is crossed 20 mesh sieve granulate, and by the mix lubricant 5min in the granule obtaining and prescription, tabletting, obtains 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 tablets preparation methoies

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

2), tablet preparation: by step 1) gained crushing material, cross 120 mesh standard sieves and obtain solid dispersion powder; Gained solid dispersion powder, dextrin 430g are put into granulator, be dry mixed 10min, add appropriate 50% ethanol moistening, setting shears frequency is 30Hz, shear granulation 10min; Material is crossed and is moved to boiling drier after the wet granulate of 30 mesh sieves and be dried to moisture 8%; Dried granule is crossed 30 mesh sieve granulate, and by the mix lubricant 10min in the granule obtaining and prescription, tabletting, obtains 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

Embodiment 3 tablet quality inspections

1, outward appearance

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

2, uniformity of dosage units

Embodiment 1,2 gained propranolol hydrochloride tablets are respectively got 10, and according to Chinese Pharmacopoeia, 2010 editions two appendix XE check uniformity of dosage units.Measure the every relative amount take labelled amount as 100, 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 tablets is good.

3, dissolution

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

Take above-mentioned foundation desirable embodiment of the present invention as enlightenment, by above-mentioned description, relevant staff can, not departing from the scope of this invention technological thought, carry out various change and modification completely.The technical scope of this invention is not limited to the content in description, must determine its technical scope according to claim scope.

Claims (2)

1. a propranolol hydrochloride tablets, write out a prescription as follows:

supplementary material title every 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 preparation method of propranolol hydrochloride tablets described in claim 1:

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

2), tablet preparation: by step 1) gained crushing material, cross 100-120 mesh standard sieve and obtain solid dispersion powder; Gained solid dispersion powder, dextrin 430g are put into granulator, be dry mixed 5-10min, add the appropriate ethanol of 40～50% (ml/ml) moistening, setting shears frequency is 20-30Hz, shear granulation 5-10min; Material is crossed and is moved to boiling drier after 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 by the mix lubricant 5-10min in the granule obtaining and prescription, tabletting, obtains 10,000.

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