CN106074428A - Naftopidil oral cavity disintegration tablet and preparation method - Google Patents

Naftopidil oral cavity disintegration tablet and preparation method Download PDF

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Publication number
CN106074428A
CN106074428A CN201610544549.6A CN201610544549A CN106074428A CN 106074428 A CN106074428 A CN 106074428A CN 201610544549 A CN201610544549 A CN 201610544549A CN 106074428 A CN106074428 A CN 106074428A
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CN
China
Prior art keywords
naftopidil
oral cavity
cavity disintegration
disintegration tablet
preparation
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
CN201610544549.6A
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Chinese (zh)
Inventor
刘丽
徐奎
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Anhui Province Yi Xinming Pharmaceutical Technology Co Ltd
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Anhui Province Yi Xinming Pharmaceutical Technology Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Anhui Province Yi Xinming Pharmaceutical Technology Co Ltd filed Critical Anhui Province Yi Xinming Pharmaceutical Technology Co Ltd
Priority to CN201610544549.6A priority Critical patent/CN106074428A/en
Publication of CN106074428A publication Critical patent/CN106074428A/en
Pending legal-status Critical Current

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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
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • 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
    • A61K9/2009—Inorganic compounds
    • 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
    • A61K9/2013—Organic compounds, e.g. phospholipids, fats
    • 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
    • A61K9/2013—Organic compounds, e.g. phospholipids, fats
    • A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
    • 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
    • A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
    • 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
    • A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms

Abstract

The invention provides a kind of naftopidil oral cavity disintegration tablet and preparation method thereof, use direct powder compression.Production technology of the present invention is simple, uniformity of dosage units good, disintegrate leaches soon, bioavailability high, it is adaptable to special population medication, especially old people and dysphagia patients.

Description

Naftopidil oral cavity disintegration tablet and preparation method
Technical field
The present invention relates to a kind of naftopidil oral cavity disintegration tablet and preparation method thereof, belong to field of pharmaceutical preparations.
Background technology
Naftopidil is a kind of novel selective α long-acting, high1-receptor blocking agent, by being selectively applied to α1A And α1D receptor, it is possible to alleviate prostate caused by this receptor excitement and the sympathetic nerve sexual tension of urethra, to reduce urethra intrinsic pressure, Increase urinary flow, improve or eliminate the urine in prostate and ejaculatory duct and backflow and be conducive to dredging prostate vessel, before eliminating Pathogen retained secretion in row gland glandular tube, thus reach improvement, symptomatolytic therapeutic purposes.It is used for treating good clinically The dysuria that property prostatic hyperplasia causes.
Due to the determined curative effect of naftopidil, untoward reaction is few, is that current Clinical practice most widely treats optimum prostatitis The dysuria medicine that gland hypertrophy causes, is primarily adapted for use in old man.Domestic listing is only tablet, and therefore, exploitation is suitable for old The novel formulation of people is the most necessary to meet the needs of clinical application.
But, due to naftopidil in water the most insoluble, dissolution rate and the dissolution of its tablet are low, as treat optimum The dysuria medicine that prostatic hyperplasia causes is for old man and dysphagia patients and depending on of taking medicine of patient in particular circumstances Poor from property, have impact on giving full play to of clinical drug curative effect.
Oral cavity disintegration tablet, as a kind of new dosage form and a kind of new administrated method, can facilitate part population medication, as always Patient's medication under people, child, dysphagia or special environment.This dosage form, compared with conventional tablet, is characterized in being not required to use water Or only need a small amount of water, without chewing, medicine is placed on tongue, meets saliva and dissolves rapidly or after disintegrate, enters stomach by means of swallowing act and rise Effect.Facilitate medication for meeting in above-mentioned suitable population and environment, We conducted the development of naftopidil oral cavity disintegration tablet, for facing Bed provides the novel form of a taking convenience, increases a kind of selection of clinical application.
Oral cavity disintegration tablet disintegrate in the oral cavity leaches the time and is usually the several seconds to several tens of seconds, is usually no more than 1 point Clock, can be not required to water or only can take with a small amount of water.The main purpose of exploitation oral cavity disintegration tablet is to improve some patients The compliance of medication, improves dissolution rate and the dissolution of medicine, quickly discharges, absorb rapidly.According to statistics, in clinical application Cheng Zhong, the Proportion of patients of swallow tablet or capsule difficulty is higher, and the gerontal patient of about 65% gulps down medicine difficulty, specialized agency supervise Also having 30%～40% old people to be difficult to independently swallow medicine in the old people protected, about 18%～22% needs the old age of long-term monitoring People cannot independently take medicine.Oral cavity disintegration tablet is particularly suitable for old people, dysphagia patients, long-term bedridden patients.
Abroad, oral cavity disintegration tablet technology of preparing is the most ripe for the sixth of the twelve Earthly Branches, such as freeze-drying, mechanography, direct compression process, spray Mist seasonings etc., though the most also part kind successfully lists, but are limited by preparation technological know-how property right, product in mouthfeel and Disintegration rate aspect is still not as good as external.At present, the oral cavity disintegration tablet of external listing is used consigned processing by patent holder Mode produces, and defines tight technology barriers.But, the oral cavity disintegration tablet technology of preparing listed all exists necessarily Defect, and it is suitable only for some specific small dose drug.At present, the development trend of oral cavity disintegration tablet technology of preparing is except keeping Outside good disintegrative, mouthfeel and mechanical strength, reduce production cost further, the heavy dose of oral cavity disintegration tablet of preparation is a kind of system One trend.
Summary of the invention
The present invention is directed to the deficiency of existing oral cavity disintegration tablet technology of preparing, use easy and simple to handle, without special producing equipment Direct powder compression with working condition, without extra package produces naftopidil oral cavity disintegration tablet, reaches to be suitable for industrialization Produce, the compressibility of tablet is good, constant product quality is controlled, rapid disintegrate in oral cavity, the nice and cool exquisiteness of mouthfeel is without grittiness, storage Transport and take convenient purpose.
The first object of the present invention is to provide a kind of naftopidil oral cavity disintegration tablet, and its supplementary material weight ratio is: naphthalene piperazine ground That 25, PEARLITOL 25C 70, aluminium-magnesium silicate 22, cross linked polyvinyl pyrrolidone 6.5, magnesium stearate 1.5.
The second object of the present invention is to provide the preparation method of a kind of naftopidil oral cavity disintegration tablet, and the method uses powder Prepared by direct compression process, specifically include following steps:
1) naftopidil being crossed 200 mesh sieves, it is standby that 100 mesh sieves crossed by remaining adjuvant；
2) naftopidil, PEARLITOL 25C, aluminium-magnesium silicate, cross linked polyvinyl pyrrolidone (PVPP), magnesium stearate are put Double helix Taper powder mixer mixes；
3) by step 2) sample under agitation flows into the mould of tablet machine by the charging basket of mixer；
4) control envionmental humidity less than 60%, by the centre that is pressed into claimed below there is marginal circular piece:
The present inventor utilizes orthogonal test to carry out prescription and the screening of technique and optimization.With disintegration as inspection target, to prescription Technique is investigated, and selects to use orthogonal design to investigate tableting pressure, PEARLITOL 25C and the ratio of aluminium-magnesium silicate, crosslinked polyethylene Arsenic pyrrolidone and magnesium stearate consumption four factors, investigate the level that they are different, filter out optimization formulation, and recycling refers to Optimization formulation is evaluated by mark, obtains the formulation and technology of the present invention further.
Naftopidil oral cavity disintegration tablet of the present invention, compared with ordinary tablet, can reduce dysphagia, improve compliance, be suitable for In special population medication, easily for old man and the disease changed with some psychiatric patient and bed position difficulty having dysphagia People is accepted；And due to the selection of adjuvant, in good taste, can be at direct drug injection under water-less environment；At digestive tract without trapping phenomena, right Digestive tract stimulates little；Release is fast, absorbs fast, provides a kind of new selection for clinic.
Obviously, according to the foregoing of the present invention, according to ordinary technical knowledge and the customary means of this area, without departing from Under the present invention above-mentioned basic fundamental thought premise, it is also possible to make the amendment of other various ways, replace or change.
Detailed description of the invention
The detailed description of the invention of form by the following examples, remakes the most specifically the foregoing of the present invention Bright.But this should not being interpreted as, the scope of the above-mentioned theme of the present invention is only limitted to Examples below.All based on foregoing of the present invention The technology realized belongs to the scope of the present invention.
Embodiment 1
Prescription:
Preparation technology:
1) naftopidil being crossed 200 mesh sieves, it is standby that 100 mesh sieves crossed by remaining adjuvant；
2) naftopidil, PEARLITOL 25C, aluminium-magnesium silicate, cross linked polyvinyl pyrrolidone (PVPP), magnesium stearate are put Double helix Taper powder mixer mixes；
3) by step 2) sample under agitation flows into the mould of tablet machine by the charging basket of mixer；
4) control envionmental humidity less than 60%, with the round punch of diameter about 7.0mm, regulate pressure about 6.1kg, compressed tablet Weigh about 125mg and thickness about 3.3mm, to obtain final product.
Embodiment 2
Prescription:
Preparation technology:
1) naftopidil being crossed 200 mesh sieves, it is standby that 100 mesh sieves crossed by remaining adjuvant；
2) naftopidil, PEARLITOL 25C, aluminium-magnesium silicate, cross linked polyvinyl pyrrolidone (PVPP), magnesium stearate are put Double helix Taper powder mixer mixes；
3) by step 2) sample under agitation flows into the mould of tablet machine by the charging basket of mixer；
4) control envionmental humidity less than 60%, with the round punch of diameter about 9.0mm, regulate pressure about 6.9kg, compressed tablet Weigh about 250mg and thickness about 4.1mm, to obtain final product.
Embodiment 3
Prescription:
Preparation technology:
1) naftopidil being crossed 200 mesh sieves, it is standby that 100 mesh sieves crossed by remaining adjuvant；
2) naftopidil, PEARLITOL 25C, aluminium-magnesium silicate, cross linked polyvinyl pyrrolidone (PVPP), magnesium stearate are put Double helix Taper powder mixer mixes；
3) by step 2) sample under agitation flows into the mould of tablet machine by the charging basket of mixer；
4) control envionmental humidity less than 60%, with the round punch of diameter about 10.0mm, regulate pressure about 7.2kg, compressed tablet Weigh about 375mg and thickness about 4.9mm, to obtain final product.
Embodiment 4 quality evaluation
1, uniformity of dosage units
Method: take this product 1, adds 10ml deionized water, ultrasonic makes dispersion disintegrate, adds methanol and dissolves clarification, then adds methanol and join Make every ml naftopidil containing 0.25mg, with the membrane filtration of 0.45 μm, discard above 10ml filtrate, take filtrate 6ml below, Add methanol to be dissolved to 50ml and shake up, as need testing solution.Another precision weighs the pre-naftopidil pair being dried 3 hours through 105 DEG C According to product 50mg, putting in 100ml measuring bottle, add methanol and dissolve and determine molten, shake up, precision measures 3ml, puts in 50ml measuring bottle, adds methanol It is diluted to scale, shakes up, as reference substance solution.Take above two solution and shine ultraviolet visible spectrophotometry, use dissolution medium Blank as mensuration, at 283nm wavelength, measure absorbance respectively, calculate content.As a result, embodiment 1, embodiment 2 and reality Execute example 3 and all meet regulation (Chinese Pharmacopoeia two annex XE of version in 2015).
2, disintegration
Taking 10ml syringe one (internal diameter 1.5cm, outlet is positioned at the centre of syringe lower end), exit, lower end is cased with one section of 2cm length Rubber tube, and with one tongs clamping, put on digestion instrument or disintegration tester and fix, in its upper end add 2ml temperature be 37 DEG C water, the lower half of syringe is immersed constant temperature 5 minutes in 37 DEG C of thermostatic circulation baths in digestion instrument or disintegration tester, adds this Product 1, start to record disintegration, and observe disintegrate situation, should complete disintegrate in 1 minute.Take out syringe, decontrol sealing Folder, makes solution pass through 30 eye mesh screens, should all pass through.Measure 6 times all should in 1 minute disintegrate completely and all by 30 mesh sieves Net.Embodiment 1, embodiment 2 and embodiment 3 all meet regulation.
3, dissolution
Take this product, according to dissolution method (paddle board method), with the NaAc_HAc buffer solution (0.05mol/L) that pH is 4.0 900ml is solvent, and rotating speed is 50 turns per minute, operates in accordance with the law, during each time point, takes solution and filters in right amount, discards at least 10ml Just filtrate, it is appropriate that precision measures subsequent filtrate, adds dissolution medium and makes the solution containing 28 μ g in every 1ml, molten as test sample Liquid.Another precision weighs the pre-naftopidil reference substance 0.028g being dried 3 hours through 105 DEG C, puts in 100ml measuring bottle, adds methanol 50ml makes dissolving, then adds dissolution medium to scale, shakes up, and precision measures 5ml, puts in 50ml measuring bottle, adds dissolution medium dilute Release to scale, shake up, as reference substance solution.Take above two solution and shine ultraviolet visible spectrophotometry, make with dissolution medium Blank for mensuration, at 283nm wavelength, measure absorbance respectively, calculate the stripping quantity of every, limit is the dissolution of 15 minutes Amount is all higher than the 85% of labelled amount.Acetonideexample 1 is 88.9, embodiment 2 is 89.0, embodiment 3 is 89.4, all meets rule Fixed.And the dissolution of ordinary tablet is 45 minutes limits is the 75% or 70% of labelled amount, therefore advantage of the present invention is apparent.
4, stability test (sample of the embodiment of the present invention 1)
。

Claims (3)

1. a naftopidil oral cavity disintegration tablet, its supplementary material weight ratio is: naftopidil 25, PEARLITOL 25C 70, silicic acid Magnalium 22, cross linked polyvinyl pyrrolidone 6.5, magnesium stearate 1.5.
2. a kind of naftopidil oral cavity disintegration tablet described in claim 1, it is characterised in that: this preparation method uses powder direct Prepared by pressed disc method.
3. the preparation method of the naftopidil oral cavity disintegration tablet described in claim 1 or 2, it is characterised in that the method include as Lower step:
1) naftopidil being crossed 200 mesh sieves, it is standby that 100 mesh sieves crossed by remaining adjuvant；
2) naftopidil, PEARLITOL 25C, aluminium-magnesium silicate, cross linked polyvinyl pyrrolidone (PVPP), magnesium stearate are put Double helix Taper powder mixer mixes；
3) by step 2) sample under agitation flows into the mould of tablet machine by the charging basket of mixer；
4) control envionmental humidity less than 60%, by the centre that is pressed into claimed below there is marginal circular piece:
。
CN201610544549.6A 2016-07-12 2016-07-12 Naftopidil oral cavity disintegration tablet and preparation method Pending CN106074428A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201610544549.6A CN106074428A (en) 2016-07-12 2016-07-12 Naftopidil oral cavity disintegration tablet and preparation method

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Application Number Priority Date Filing Date Title
CN201610544549.6A CN106074428A (en) 2016-07-12 2016-07-12 Naftopidil oral cavity disintegration tablet and preparation method

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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2004175796A (en) * 2002-11-13 2004-06-24 Asahi Kasei Pharma Kk Intraoral disintegrating preparation for treating dysuria
JP5208348B2 (en) * 2004-05-13 2013-06-12 旭化成ファーマ株式会社 Medicine containing naphthopidyl
JP2015017056A (en) * 2013-07-10 2015-01-29 共和薬品工業株式会社 Intraoral disintegrable tablet

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2004175796A (en) * 2002-11-13 2004-06-24 Asahi Kasei Pharma Kk Intraoral disintegrating preparation for treating dysuria
JP5208348B2 (en) * 2004-05-13 2013-06-12 旭化成ファーマ株式会社 Medicine containing naphthopidyl
JP2015017056A (en) * 2013-07-10 2015-01-29 共和薬品工業株式会社 Intraoral disintegrable tablet

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Application publication date: 20161109