CN111743871B - Phenobenzmine hydrochloride tablet and preparation method thereof - Google Patents

Phenobenzmine hydrochloride tablet and preparation method thereof Download PDF

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CN111743871B
CN111743871B CN202010674871.7A CN202010674871A CN111743871B CN 111743871 B CN111743871 B CN 111743871B CN 202010674871 A CN202010674871 A CN 202010674871A CN 111743871 B CN111743871 B CN 111743871B
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dextrin
phenoxybenzamine hydrochloride
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pregelatinized starch
phenoxybenzamine
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CN111743871A (en
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吴严
毛新付
陈琦
黄鸳鸯
徐文斌
李青霞
樊静
王凌志
高威
古东霞
冯荣彬
刘继方
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Topfond Pharma Co ltd
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
    • A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/13—Amines
    • A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
    • A61K31/138—Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2095—Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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    • A—HUMAN NECESSITIES
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    • A—HUMAN NECESSITIES
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/06—Antiarrhythmics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
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Abstract

The invention discloses a phenoxybenzamine hydrochloride tablet which comprises the following components: phenoxybenzamine hydrochloride, dextrin, pregelatinized starch, a disintegrant, a filler, a binder, a lubricant and a glidant. The viscosity of the dextrin is 4.5-8.5 mpa.s; the specific surface area of the pregelatinized starch is less than or equal to 350m2Per kg; the disintegrant is carboxymethyl starch sodium. Adding disintegrating agent such as carboxymethyl starch sodium, dextrin with viscosity of 4.5-8.5mpa.s, and specific surface area of 350m or less2The pregelatinized starch/kg can ensure that the obtained phenoxybenzamine hydrochloride tablet has improved dissolution rate and dissolution rate uniformity, small difference in groups and good stability.

Description

Phenobenzmine hydrochloride tablet and preparation method thereof
Technical Field
The invention relates to the technical field of preparation of medicinal preparations, in particular to a phenoxybenzamine hydrochloride tablet and a preparation method thereof.
Background
The chemical name of phenoxybenzamine hydrochloride is: n- (1-methyl-2-phenoxyethyl) -N- (2-chloroethyl) benzylamine hydrochloride, the structural formula of which is as follows:
Figure BDA0002583678980000011
phenoxybenzamine hydrochloride can change vasoconstriction reaction generated by exciting alpha-receptor, reduce the resistance of peripheral blood vessels and relieve the capacity of the blood vessels in constriction state, thereby increasing the blood vessel capacity by 20-30%; has the functions of increasing myocardial contraction, increasing heart rate, lowering blood pressure, reducing peripheral vascular resistance, increasing cardiac output, reducing oxygen consumption and the like; also has antihistaminic effect, and can increase urine volume of shock patients and make skin red and warm. The indications of phenoxybenzamine hydrochloride are as follows: (1) treatment and preoperative preparation of pheochromocytoma; (2) peripheral vasospastic disorders; (3) urinary retention due to prostatic hyperplasia.
The current commercial products are the phenoxybenzamine hydrochloride tablets, and the current phenoxybenzamine hydrochloride tablet products have the problems of low dissolution rate and large batch-to-batch and batch-to-batch difference through practice. Therefore, a method is needed to solve the current technical problems.
The information disclosed in this background section is only for enhancement of understanding of the general background of the invention and should not be taken as an acknowledgement or any form of suggestion that this information forms the prior art already known to a person skilled in the art.
Disclosure of Invention
The invention aims to provide a phenoxybenzamine hydrochloride tablet which has improved dissolution rate and dissolution rate uniformity, small intra-group difference and good stability.
In order to achieve the above object, the present invention provides a phenoxybenzamine hydrochloride tablet, which comprises the following components: phenoxybenzamine hydrochloride, dextrin, pregelatinized starch, a disintegrant, a filler, a binder, a lubricant and a glidant.
In a preferred embodiment, the weight parts of the components are as follows: 5-25 parts of phenoxybenzamine hydrochloride, 2-15 parts of dextrin, 30-70 parts of pregelatinized starch, 2-10 parts of disintegrating agent, 10-40 parts of filler, 3-25 parts of adhesive, 1-4 parts of lubricant and 1-8 parts of glidant; preferably, the weight parts of the components are as follows: 10-20 parts of phenoxybenzamine hydrochloride, 4-10 parts of dextrin, 35-50 parts of pregelatinized starch, 3-8 parts of disintegrating agent, 15-30 parts of filling agent, 5-15 parts of adhesive, 1-3 parts of lubricant and 1-5 parts of glidant; most preferably, the weight parts of the components are as follows: 12-15 parts of phenoxybenzamine hydrochloride, 4.5-6 parts of dextrin, 40-45 parts of pregelatinized starch, 4-6 parts of a disintegrating agent, 20-25 parts of a filling agent, 7-12 parts of an adhesive, 1-2 parts of a lubricant and 2-3 parts of a glidant.
In a preferred embodiment, the dextrin has a viscosity of 4.5 to 8.5 mpa.s; preferably, the viscosity of said dextrin is 5.5-7.0 mpa.s; most preferably, the dextrin has a viscosity of 6.2 mpa.s.
The inventor finds that the relationship between the dextrin viscosity and the dissolution rate of the product is relatively large, namely the higher the dextrin viscosity is, the larger the intrinsic binding force of the prepared granules is, the better the particle compressibility is, and the lower the dissolution rate of the tablet core is, on the contrary, the lower the dextrin viscosity is, the smaller the intrinsic binding force of the prepared granules is, the poorer the particle compressibility is, and the higher the dissolution rate of the tablet core is. Therefore, in order to ensure that the compressibility of phenoxybenzamine hydrochloride particles and the dissolution rate of a product meet the requirements in the preparation process of phenoxybenzamine hydrochloride tablets, dextrin with the viscosity of 4.5-8.5mpa.s and preferably in the range of 5.5-7.0mpa.s is selected to be used as a binder and a filler, so that the drug forming is facilitated, and the drug powder is aggregated into particles.
In a preferred embodiment, the specific surface area of the pregelatinized starch is 350m or less2Per kg; preferably, the specific surface area of the pregelatinized starch is less than or equal to 200m2Per kg; most preferably, the pregelatinized starch has a specific surface area of 160.3m2/kg。
The inventors found that the specific surface area of pregelatinized starch had a large effect on oral solid formulations. If the particle size of the pregelatinized starch is reducedThe specific surface area of the pregelatinized starch is increased, so that the components of the preparation can be mixed and dispersed uniformly, and the dissolution rate of the preparation is improved; if the particle size of the pregelatinized starch is increased and the specific surface area of the pregelatinized starch is reduced, granulation can be facilitated and tabletting compliance can be increased. The inventor synthesizes the dissolution rate result of the product and the compliance of the tabletting process, and finally determines that the specific surface area is less than or equal to 350m2The pregelatinized starch/kg is used as filler, which is beneficial to forming the medicine and improving the compressibility of the granule.
In a preferred embodiment, the disintegrant is one or more of carboxymethyl starch sodium, crospovidone, croscarmellose sodium and low substituted hydroxypropyl cellulose; preferably, the disintegrant is sodium starch glycolate.
The sodium carboxymethyl starch is used as a disintegrating agent, which can absorb water rapidly and achieve rapid and remarkable swelling, thereby playing a role in disintegrating, promoting the release of the medicament and meeting the requirement of dissolution within a specified time; in addition, the carboxymethyl starch sodium is cheap and widely used. Thus, the inventors selected sodium starch glycolate as the disintegrant.
In a preferred embodiment, the filler is one or more selected from the group consisting of starch, microcrystalline cellulose, lactose, mannitol, and dextrin; preferably, the filler is microcrystalline cellulose.
In a preferred embodiment, the binder is one or more selected from the group consisting of dextrin pulp, hypromellose, povidone, hyprolose, and ethylcellulose; preferably, the binder is a dextrin paste; most preferably, the adhesive is dextrin pulp with the mass percentage concentration of 20 percent;
and/or, the lubricant is selected from one or more of sodium stearyl fumarate, magnesium stearate, stearic acid, talcum powder and superfine silica powder; preferably, the lubricant is magnesium stearate;
and/or the glidant is selected from one or more of talcum powder, superfine silica gel powder and silicon dioxide; preferably, the glidant is silicon dioxide.
Another object of the present invention is to provide a method for preparing the phenoxybenzamine hydrochloride tablet, which comprises the steps of:
(1) crushing and sieving phenoxybenzamine hydrochloride, and directly weighing other components for later use;
(2) uniformly mixing phenoxybenzamine hydrochloride, dextrin, pregelatinized starch and a filler, spraying an adhesive, performing further granulation, drying, and then granulating to obtain granules;
(3) uniformly mixing the granules obtained in the step (2) with a lubricant, a glidant and a disintegrant to obtain final granules; and
(4) and (4) tabletting the granules obtained in the step (3) to obtain the phenoxybenzamine hydrochloride tablets.
In a preferred embodiment, in the step (1), the phenoxybenzamine hydrochloride is crushed and sieved by a sieve of 80-120 meshes; preferably, the phenoxybenzamine hydrochloride is crushed and sieved by a 100-mesh sieve.
In a preferred embodiment, in the step (2), the drying is performed by using a fluidized bed drying granulator, and the drying temperature is 45-65 ℃, and the preferred temperature is 55 ℃; the mesh size of the grading sieve is 1.5mm during grading, the grading frequency is 5-15Hz, and the preferred grading frequency is 10 Hz.
Compared with the prior art, the invention has the following beneficial effects:
(1) the dextrin with the viscosity of 4.5-8.5mpa.s, preferably 5.5-7.0mpa.s is used as the adhesive and the filler, so that the internal binding force of the particles prepared in the preparation process of the phenoxybenzamine hydrochloride tablet is increased, the particle compressibility is good, the dissolution rate of the tablet core is reduced, the compressibility of the phenoxybenzamine hydrochloride particles and the dissolution rate of the product in the preparation process of the phenoxybenzamine hydrochloride tablet are ensured to meet the requirements, the drug forming is facilitated, and the drug powder is aggregated into particles.
(2) The invention adopts the specific surface area of less than or equal to 350m2The pregelatinized starch/kg is used as a filler, so that the components of the preparation can be mixed and uniformly dispersed, the dissolution rate of the preparation is improved, the granulation is facilitated, and the tabletting compliance is increased. The inventor finally determines that the specific surface area is less than or equal to 350m by combining the dissolution rate result of the product and the compliance of the tabletting process2Perkg of pregelatinized starchAs a filler, the powder is beneficial to forming the medicine and improves the compressibility of the granules.
(3) In addition, the drying process of the invention greatly improves the dissolution rate and stability of the phenoxybenzamine hydrochloride tablets.
In conclusion, the phenoxybenzamine hydrochloride is a poorly soluble substance, and the inventors have found through experiments that when the composition does not contain a disintegrant such as carboxymethyl starch sodium, and/or the viscosity of the selected dextrin is not in the range of 4.5 to 8.5mpa.s, and/or the specific surface area of the selected pregelatinized starch is more than 350m2Kg, the disintegration time of the obtained phenoxybenzamine hydrochloride tablet is greatly prolonged, compared with the method that a disintegrating agent such as carboxymethyl starch sodium, dextrin with the viscosity of 4.5-8.5mpa.s and dextrin with the specific surface area less than or equal to 350m are added simultaneously2The disintegration time of the/kg pregelatinized starch is extended by at least 3 times. In addition, the components are added with disintegrant such as carboxymethyl starch sodium, dextrin with viscosity of 4.5-8.5mpa.s, and specific surface area of 350m or less2The pregelatinized starch/kg has a viscosity of 4.5-8.5mpa.s and/or a specific surface area of more than 350m2Compared with the situation of/kg, the reduced rate of the dissolution rate is lower, the dissolution rate is more uniform, the difference between the maximum value and the minimum value is 3.3 percent, the difference in groups is small, and the stability of the phenoxybenzamine hydrochloride tablet is good.
Detailed Description
The following detailed description of specific embodiments of the invention is provided, but it should be understood that the scope of the invention is not limited to the specific embodiments.
Throughout the specification and claims, unless explicitly stated otherwise, the word "comprise", or variations such as "comprises" or "comprising", will be understood to imply the inclusion of a stated element or component but not the exclusion of any other element or component.
Example 1
A phenoxybenzamine hydrochloride tablet, which comprises the following components:
Figure BDA0002583678980000051
Figure BDA0002583678980000061
wherein the dextrin has viscosity of 6.2MPa.s, and the pregelatinized starch has specific surface area of 160.3m2/kg。
The preparation method of the phenoxybenzamine hydrochloride tablet comprises the following steps: (1) crushing phenoxybenzamine hydrochloride, sieving the crushed phenoxybenzamine hydrochloride with a 100-mesh sieve, and directly weighing other components for later use; dispersing dextrin (dextrin in dextrin pulp) in a small amount of cold water, adding boiling water, and continuously stirring to obtain 20% dextrin pulp for later use; (2) uniformly mixing phenoxybenzamine hydrochloride, microcrystalline cellulose, dextrin and pregelatinized starch, spraying dextrin slurry with the mass percentage concentration of 20% for one-step granulation, and granulating the prepared wet granules in a fluidized bed drying granulator until the temperature is 55 ℃, wherein the mesh size of the granulating sieve is 1.5mm, and the granulating frequency is 10 Hz; (3) uniformly mixing the granules with magnesium stearate, silicon dioxide and carboxymethyl starch sodium to obtain final granules; (4) the resulting granules were compressed into tablets using a tablet press machine to obtain the final phenoxybenzamine hydrochloride tablets, wherein the die used was a 5.5mm shallow concave punch die.
Example 2
A phenoxybenzamine hydrochloride tablet, which comprises the following components:
name of material Dosage (% by weight) Function(s)
Phenoxybenzamine hydrochloride 10 Active ingredient
Microcrystalline cellulose 16 Filler
Dextrin 8 Filler
20% dextrin syrup 5 (paste quantity) Adhesive agent
Pregelatinized starch 35 Filler and disintegrant
Magnesium stearate 1 Lubricant agent
Silicon dioxide 3 Glidants
Sodium starch glycolate 3 Disintegrating agent
Wherein the dextrin has viscosity of 7.0MPa.s, and the pregelatinized starch has specific surface area of 180m2/kg。
The preparation method of the phenoxybenzamine hydrochloride tablet comprises the following steps: (1) crushing phenoxybenzamine hydrochloride, sieving the crushed phenoxybenzamine hydrochloride with a 100-mesh sieve, and directly weighing other components for later use; dispersing dextrin (dextrin in dextrin pulp) in a small amount of cold water, adding boiling water, and continuously stirring to obtain 20% dextrin pulp for later use; (2) uniformly mixing phenoxybenzamine hydrochloride, microcrystalline cellulose, dextrin and pregelatinized starch, spraying dextrin slurry with the mass percentage concentration of 20% for one-step granulation, and carrying out granulation on the prepared wet granules when the wet granules are dried to 45 ℃ in a fluidized bed drying granulator, wherein the aperture of a granulating screen is 1.5mm, and the granulating frequency is 7 Hz; (3) uniformly mixing the granules with magnesium stearate, silicon dioxide and carboxymethyl starch sodium to obtain final granules; (4) the resulting granules were compressed into tablets using a tablet press machine to obtain the final phenoxybenzamine hydrochloride tablets, wherein the die used was a 5.5mm shallow concave punch die.
Example 3
A phenoxybenzamine hydrochloride tablet, which comprises the following components:
name of material Dosage (% by weight) Function(s)
Phenoxybenzamine hydrochloride 20 Active ingredient
Microcrystalline cellulose 28 Filler
Dextrin 10 Filler
20% dextrin syrup 15 (paste quantity) Adhesive agent
Pregelatinized starch 50 Filler and disintegrant
Magnesium stearate 2 Lubricant agent
Silicon dioxide 3 Glidants
Sodium starch glycolate 6 Disintegrating agent
Wherein the dextrin has viscosity of 5.5MPa.s, and the pregelatinized starch has specific surface area of 130m2/kg。
The preparation method of the phenoxybenzamine hydrochloride tablet comprises the following steps: (1) crushing phenoxybenzamine hydrochloride, sieving the crushed phenoxybenzamine hydrochloride with a 100-mesh sieve, and directly weighing other components for later use; dispersing dextrin (dextrin in dextrin pulp) in a small amount of cold water, adding boiling water, and continuously stirring to obtain 20% dextrin pulp for later use; (2) uniformly mixing phenoxybenzamine hydrochloride, microcrystalline cellulose, dextrin and pregelatinized starch, spraying dextrin slurry with the mass percentage concentration of 20% for one-step granulation, and carrying out granulation on the prepared wet granules when the wet granules are dried to 65 ℃ in a fluidized bed drying granulator, wherein the aperture of a granulating screen is 1.5mm, and the granulating frequency is 15 Hz; (3) uniformly mixing the granules with magnesium stearate, silicon dioxide and carboxymethyl starch sodium to obtain final granules; (4) the resulting granules were compressed into tablets using a tablet press machine to obtain the final phenoxybenzamine hydrochloride tablets, wherein the die used was a 5.5mm shallow concave punch die.
Example 4
A phenoxybenzamine hydrochloride tablet, which comprises the following components:
name of material Dosage (% by weight) Function(s)
Phenoxybenzamine hydrochloride 12 Active ingredient
Microcrystalline cellulose 24 Filler
Dextrin 6 Filler
20% dextrin syrup 12 (paste quantity) Adhesive agent
Pregelatinized starch 45 Filler and disintegrant
Magnesium stearate 1.3 Lubricant agent
Silicon dioxide 2.3 Glidants
Sodium starch glycolate 5.5 Disintegrating agent
Wherein the dextrin has viscosity of 6.5MPa.s, and the pregelatinized starch has specific surface area of 200m2/kg。
The preparation method of the phenoxybenzamine hydrochloride tablet comprises the following steps: (1) crushing phenoxybenzamine hydrochloride, sieving the crushed phenoxybenzamine hydrochloride with a 100-mesh sieve, and directly weighing other components for later use; dispersing dextrin (dextrin in dextrin pulp) in a small amount of cold water, adding boiling water, and continuously stirring to obtain 20% dextrin pulp for later use; (2) uniformly mixing phenoxybenzamine hydrochloride, microcrystalline cellulose, dextrin and pregelatinized starch, spraying dextrin slurry with the mass percentage concentration of 20% for one-step granulation, and carrying out granulation on the prepared wet granules when the wet granules are dried to 50 ℃ in a fluidized bed drying granulator, wherein the aperture of a granulating screen is 1.5mm, and the granulating frequency is 12 Hz; (3) uniformly mixing the granules with magnesium stearate, silicon dioxide and carboxymethyl starch sodium to obtain final granules; (4) the resulting granules were compressed into tablets using a tablet press machine to obtain the final phenoxybenzamine hydrochloride tablets, wherein the die used was a 5.5mm shallow concave punch die.
Comparative example 1
A phenoxybenzamine hydrochloride tablet, which comprises the following components:
name of material Dosage (% by weight) Function(s)
Phenoxybenzamine hydrochloride 13.4 Active ingredient
Microcrystalline cellulose 21.4 Filler
Dextrin 5.1 Filler
20% dextrin syrup 9.9 (paste quantity) Adhesive agent
Pregelatinized starch 42.0 Filler and disintegrant
Magnesium stearate 1.2 Lubricant agent
Silicon dioxide 2.1 Glidants
Sodium starch glycolate 5.0 Disintegrating agent
Comparative example 1 the components and amounts and the procedure were the same as in example 1, except that the viscosity of dextrin and the specific surface area of pregelatinized starch were different from those of example 1. The dextrin used in comparative example 1 had a viscosity of 23.3MPa.s and the pregelatinized starch had a specific surface area of 436.3m2/kg。
Comparative example 2
Comparative example 2 the components and amounts and the procedure were the same as in example 1 except that the viscosity of dextrin was different from that of example 1, but the specific surface area of pregelatinized starch was almost the same as that of example 1. The dextrin used in comparative example 2 had a viscosity of 24.0MPa.s and the pregelatinized starch had a specific surface area of 178.8m2/kg。
Comparative example 3
Comparative example 3 the components and amounts and the procedure were the same as in example 1, except that the specific surface area of the pregelatinized starch was different from that of example 1, but the viscosity of the dextrin was almost the same as that of example 1. The dextrin used in comparative example 2 had a viscosity of 6.5MPa.s and the pregelatinized starch had a specific surface area of 436.3m2/kg。
Comparative example 4
A phenoxybenzamine hydrochloride tablet, which comprises the following components:
name of material Dosage (% by weight) Function(s)
Phenoxybenzamine hydrochloride 13.4 Active ingredient
Microcrystalline cellulose 21.4 Filler
Dextrin 5.1 Filler
20% dextrin syrup 9.9 (paste quantity) Adhesive agent
Pregelatinized starch 42.0 Filler and disintegrant
Magnesium stearate 1.2 Lubricant agent
Silicon dioxide 2.1 Glidants
Comparative example 4 the components and amounts and the procedure were the same as in example 1, and the viscosity of the dextrin and the specific surface area of the pregelatinized starch were also the same as in example 1, i.e., the viscosity of the dextrin was 6.2MPa.s and the specific surface area of the pregelatinized starch was 160.3m2In terms of/kg. However, in contrast, comparative example 4 contained no disintegrant sodium carboxymethyl starch.
Comparative example 5
Comparative example 5 the components and amounts were the same as in example 1, and the viscosity and pregelatinized starch of dextrinThe specific surface area of the powder was also the same as in example 1, i.e. the viscosity of the dextrin was 6.2MPa.s and the specific surface area of the pregelatinized starch was 160.3m2In terms of/kg. In contrast to the procedure (2), comparative example 5 was dried in an oven at 55 degrees, and example 1 was prepared by drying the resulting wet granulation in a fluid bed dryer granulator.
Results of the experiment
(1) Examination of appearance, disintegration time, and weight variation
Sample (I) Appearance of the product Disintegration time limit Difference in weight
Example 1 The surface of the sheet is smooth and complete and shows white 2 minutes and 40 seconds Meets the requirement of +/-6.5 percent
Comparative example 1 The surface of the sheet is smooth and complete and shows white 8 minutes and 10 seconds Meets the requirement of +/-6.5 percent
Comparative example 2 The surface of the sheet is smooth and complete and shows white 6 minutes and 2 seconds Meets the requirement of +/-6.5 percent
Comparative example 3 The surface of the sheet is smooth and complete and shows white 6 minutes and 4 seconds Meets the requirement of +/-6.5 percent
Comparative example 4 The surface of the sheet is smooth and complete and shows white 7 minutes and 30 seconds Meets the requirement of +/-6.5 percent
Comparative example 5 Pocked on the surface of the sheet 12 minutes and 5 seconds Out of. + -. 6.5% requirement
As can be seen from the above table:
in comparative example 1, the viscosity of dextrin and the specific surface area of pregelatinized starch are both greater than those of example 1, and the disintegration time of the obtained phenoxybenzamine hydrochloride tablet is 8 minutes and 10 seconds, which is greatly prolonged compared with 2 minutes and 40 seconds in example 1; in comparative example 2, the viscosity of dextrin alone was higher than that of example 1, and in comparative example 3, the specific surface area of pregelatinized starch alone was higher than that of example 1, but the disintegration time of the phenoxybenzamine hydrochloride tablets was more than 6 minutes, which was also greatly prolonged as compared with 2 minutes and 40 seconds in example 1. Therefore, the viscosity of dextrin and the specific surface area of pregelatinized starch both have obvious influence on the disintegration time of the phenoxybenzamine hydrochloride tablet, and the selection of the viscosity of dextrin and the specific surface area of pregelatinized starch in a proper range is greatly helpful for reducing the disintegration time of the phenoxybenzamine hydrochloride tablet.
Comparative example 4 does not contain the disintegrant carboxymethyl starch sodium, but the disintegration time of the resulting phenoxybenzamine hydrochloride tablet reaches 7 minutes 30 seconds, which is far more than the disintegration time of 2 minutes 40 seconds in example 1. Therefore, the disintegrating agent of carboxymethyl starch sodium has great influence on reducing the disintegration time of the phenoxybenzamine hydrochloride tablet.
Comparative example 5 the drying apparatus in operation (2) was changed from a fluidized bed drying granulator to an oven, and the obtained phenoxybenzamine hydrochloride tablets had not only a longer disintegration time but also pocked and non-smooth surfaces, and had inferior appearance and weight differences to those of example 1.
(2) Examination of dissolution and content
The detection methods of dissolution and content are both in the second part of the 2015 edition of Chinese pharmacopoeia. According to the regulations of the Chinese pharmacopoeia, the examples and each comparative example have 6 data, and the specific test results are as follows:
sample (I) Dissolution rate Content (wt.)
Example 1 96.5%, 96.9%, 94.2%, 95.4%, 94.3%, 93.6%, average 95.2% 101.2％
Comparative example 1 69.0%, 71.6%, 85.0%, 73.7%, 69.8%, an average of 73.2% 100.6％
Comparative example 2 81.6%, 91.0%, 88.5%, 88.0%, 80.0%, 73.5%, average 83.8% 99.7％
Comparative example 3 84.0%, 71.1%, 93.4%, 81.3%, 77.4%, 83.5%, average 81.8% 100.5％
Comparative example 4 80.1%, 75.7%, 74.8%, 81.4%, 75.0%, 73.9%, average 76.8% 100.1％
Comparative example 5 71.4%, 64.6%, 66.8%, 73.4%, 68.4%, 64.8%, average 68.2% 99.9％
As can be seen from the above table: all indexes of the product in the embodiment 1 are superior to those of the products in the comparative examples 1-5, the dissolution rate of the product in the embodiment 1 is more uniform, the difference between the maximum value and the minimum value is 3.3%, the dissolution rates of the products in the comparative examples 1-5 are lower and have larger difference, and the difference between the maximum value and the minimum value is about 10% -20%. This indicates that the viscosity of dextrin, the specific surface area of pregelatinized starch and the disintegrant have a significant effect on the improvement of the dissolution rate and the dissolution rate uniformity of the phenoxybenzamine hydrochloride tablets.
(3) Comparative stability test
According to the Chinese pharmacopoeia, 6 data are recorded in the examples and each comparative example. The test conditions are as follows: temperature: (30 ± 2) ° c, relative humidity: (75 ± 5)%, time: and 12 months.
Figure BDA0002583678980000121
Figure BDA0002583678980000131
As can be seen from the above table: the dissolution rate of the comparative examples 1 to 5 is reduced by far more than that of the example 1, and the difference in the groups of the comparative examples 1 to 5 is larger than that of the example 1, so that the stability of the phenoxybenzamine hydrochloride tablets obtained in the example 1 is good; comparative example 5 compared to example 1, shows that the preparative drying process of the present invention provides a great improvement in the dissolution rate of phenoxybenzamine hydrochloride tablets.
It should be noted that: the legal limit of the content is 90-110%, and the tablet core content is close to 100% as much as possible when a manufacturing enterprise performs tabletting under general conditions. However, in the actual production process, due to the comprehensive factors such as the control precision and the inspection error of the tablet press, the content in the table is over 100%, but the situation still meets the legal limit and the internal control limit of the enterprise.
The foregoing descriptions of specific exemplary embodiments of the present invention have been presented for purposes of illustration and description. It is not intended to limit the invention to the precise form disclosed, and obviously many modifications and variations are possible in light of the above teaching. The exemplary embodiments were chosen and described in order to explain certain principles of the invention and its practical application to enable one skilled in the art to make and use various exemplary embodiments of the invention and various alternatives and modifications as are suited to the particular use contemplated. It is intended that the scope of the invention be defined by the claims and their equivalents.

Claims (10)

1. The phenoxybenzamine hydrochloride tablet is characterized by comprising the following components: phenoxybenzamine hydrochloride, dextrin, pregelatinized starch, a disintegrant, a filler, a binder, a lubricant, and a glidant;
the viscosity of the dextrin is 4.5-8.5mpa.s, and the specific surface area of the pregelatinized starch is less than or equal to 350m2Per kg, the disintegrant is sodium starch glycolate;
the phenoxybenzamine hydrochloride tablet is dried by adopting a fluidized bed drying granulator, and the drying temperature is 45-65 ℃; the mesh size of the whole grain sieve is 1.5mm when the whole grain is finished, and the whole grain frequency is 5-15 Hz.
2. The phenoxybenzamine hydrochloride tablet according to claim 1, wherein the weight parts of the components are: 12-15 parts of phenoxybenzamine hydrochloride, 4.5-6 parts of dextrin, 40-45 parts of pregelatinized starch, 4-6 parts of a disintegrating agent, 20-25 parts of a filling agent, 7-12 parts of an adhesive, 1-2 parts of a lubricant and 2-3 parts of a glidant.
3. The phenoxybenzamine hydrochloride tablet of claim 1, wherein the dextrin has a viscosity of 6.2 mpa.s.
4. The phenoxybenzamine hydrochloride tablet of claim 1, wherein the pregelatinized starch has a specific surface area of 160.3m2/kg。
5. The phenoxybenzamine hydrochloride tablet of claim 1, wherein the filler is microcrystalline cellulose.
6. The phenoxybenzamine hydrochloride tablet of claim 1, wherein the binder is selected from one or more of dextrin pulp, hypromellose, povidone, hydroxypropylcellulose, ethylcellulose;
and/or the lubricant is selected from one or more of sodium stearyl fumarate, magnesium stearate, stearic acid, talcum powder and superfine silica powder;
and/or the glidant is selected from one or more of talcum powder, superfine silica gel powder and silicon dioxide.
7. The phenoxybenzamine hydrochloride tablet of claim 6, wherein the binder is a dextrin syrup having a concentration of 20% by mass;
and/or, the lubricant is magnesium stearate;
and/or, the glidant is silicon dioxide.
8. The method of preparing phenoxybenzamine hydrochloride tablets of claim 1, wherein the method comprises the steps of:
(1) crushing and sieving phenoxybenzamine hydrochloride, and directly weighing other components for later use;
(2) uniformly mixing phenoxybenzamine hydrochloride, dextrin, pregelatinized starch and a filler, spraying an adhesive, performing further granulation, drying, and then granulating to obtain granules;
(3) uniformly mixing the granules obtained in the step (2) with a lubricant, a glidant and a disintegrant to obtain final granules; and
(4) and (4) tabletting the granules obtained in the step (3) to obtain the phenoxybenzamine hydrochloride tablet.
9. The method according to claim 8, wherein in the step (1), the phenoxybenzamine hydrochloride is pulverized and passed through a 100-mesh sieve.
10. The method according to claim 8, wherein in the step (2), the drying is performed by using a fluidized bed drying granulator, and the temperature during the drying is 55 ℃; when the whole grains are finished, the mesh diameter of the whole grain sieve is 1.5mm, and the whole grain frequency is 10 Hz.
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