CN102579381B - Guanidine hydrochloride sustained release preparation and preparation method thereof - Google Patents
Guanidine hydrochloride sustained release preparation and preparation method thereof Download PDFInfo
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Abstract
The invention discloses guanidine hydrochloride sustained release preparation and a preparation method thereof. The guanidine hydrochloride sustained release preparation is mainly prepared by guanidine hydrochloride, a filling agent, sustained release materials and potential of hydrogen (pH) sensitive materials. The preparation method comprises the steps of firstly preparing all raw materials according to proportion, evenly mixing the guanidine hydrochloride, the filling agent, the sustained release materials and the pH sensitive materials at high speed, granulating and drying the evenly mixed powder, finally adding a flow agent, a lubrication agent and an adhesion agent, tableting according to a general method, and achieving guanidine hydrochloride sustained release tablets. The guanidine hydrochloride sustained release preparation is small in side effect, obviously reduces difference of preparation of different batches, improves stability of samples, is convenient long term curing of patients and improves compliance of medicine. A patient can take the guanidine hydrochloride sustained release tablets once a day, so that effective drug concentration in bodies can be guaranteed for 24 hours, and nervous centralis side reactions caused by the fact that a blood concentration peak value is high due to general preparation is reduced.
Description
Technical field
The present invention relates to pharmaceutical field about drug preparation technique, particularly relate to a kind of Guanfacine Hydrochloride slow releasing preparation and preparation method thereof.
Background technology
Guanfacine Hydrochloride belongs to antihypertensive drug, is used for the treatment of moderate to severe hypertension.Chemical name is N-amidino groups-2-(2, the 6-Dichlorobenzene base) the acetamide mono-hydrochloric salts, its molecular formula is: C
9H
9Cl
2N
3OHCl, molecular weight are 282.55, and structural formula is:
Guanfacine Hydrochloride be white to the off-white color crystalline powder, be insoluble in water and ethanol, higher relatively dissolubility (〉 30mg/mg is arranged in methanol).
Guanfacine Hydrochloride is selectivity α
2-adrenoceptor synergist is used for the treatment of moderate the earliest to severe hypertension, with the tablet administration of oral administration, at the commodity of U.S. Tenex by name
, specification is 1mg or 2mg.
Because this medicine of Guanfacine Hydrochloride has very strong central action, and this medicine plasma protein binding rate height, the general formulation rate of release is too fast to make that the blood drug level peak value is higher, brings out its side effect, as drowsiness, dizziness, difficulty falling asleep, feel sick, vomiting, forgetful etc.
SHIRE companies in 2009 have obtained the approval of Guanfacine Hydrochloride slow releasing preparation first at FDA; because slow release formulation can effectively reduce Cmax; prolong drug action time; can be used for new indication-attention deficit and move obstacle (Attention-deficit hyperactivity disorder more; ADHD) treatment; evident in efficacy; those children that suffer from ADHD and behavior disorder simultaneously are particularly useful, and have relevant United States Patent (USP) to protect the Therapeutic Method of this Guanfacine Hydrochloride slow release medication.Guanfacine Hydrochloride dissolubility in the solution of different pH is obviously different, has significant pH dependency, and dissolubility is better in acid, and along with the rising of pH, dissolubility significantly reduces.Therefore, usually there are the following problems between the resulting slow releasing preparation of common preparation method: pharmacokinetic parameters such as differences between batches are big, release poor stability, the interior bioavailability of body are undesirable.
Summary of the invention
The objective of the invention is the defective that exists at Guanfacine Hydrochloride slow releasing preparation traditional preparation process method, providing a kind of is the slow releasing preparation and preparation method thereof of principal agent with the Guanfacine Hydrochloride.Utilize the Guanfacine Hydrochloride slow releasing preparation toxic and side effects of technical solution of the present invention preparation few, be convenient to patient's long-term treatment, and improved the compliance of medication.Take the Guanfacine Hydrochloride slow releasing tablet of technical solution of the present invention preparation, take every day and once can guarantee the 24 hours interior active drug concentration of body, and can reduce the higher nervus centralis side reaction that causes of blood drug level peak value that ordinary preparation brings.The present invention has adopted new recipe and new technology to prepare the Guanfacine Hydrochloride slow releasing preparation simultaneously, has significantly reduced the preparation differences between batches and has improved stability of sample.
In order to address the above problem, the technical solution used in the present invention is:
The invention provides a kind of Guanfacine Hydrochloride slow releasing preparation, represent with weight portion, described Guanfacine Hydrochloride slow releasing preparation contains 0.2～4 part of Guanfacine Hydrochloride in forming, 10～50 parts of 10～60 parts of filleies and slow-release materials.
According to above-mentioned Guanfacine Hydrochloride slow releasing preparation, described Guanfacine Hydrochloride slow releasing preparation also contains 1～40 part of pH sensitive material in forming.
According to above-mentioned Guanfacine Hydrochloride slow releasing preparation, described Guanfacine Hydrochloride slow releasing preparation contains 0.4～3 part of Guanfacine Hydrochloride in forming, 25～45 parts of filleies, 10～30 parts of 15～45 parts of slow-release materials and pH sensitive materials.
According to above-mentioned Guanfacine Hydrochloride slow releasing preparation, described Guanfacine Hydrochloride slow releasing preparation also contains 1～40 part of pH sensitive material in forming, 0.1～1 part of fluidizer, 0.1～10 part of 0.1～1 part of lubricant and binding agent.
According to above-mentioned Guanfacine Hydrochloride slow releasing preparation, described Guanfacine Hydrochloride slow releasing preparation is by 0.4～3 part of raw material Guanfacine Hydrochloride, 25～45 parts of filleies, 15～45 parts of slow-release materials, 10～30 parts of pH sensitive materials, 0.1～1 part of fluidizer, 0.1～1 part of lubricant and 0.1～10 part of composition of binding agent.
According to above-mentioned Guanfacine Hydrochloride slow releasing preparation, described filler is any one or more in sucrose, lactose, mannitol, starch, microcrystalline Cellulose, Sargassum polysaccharides, citric acid, fumaric acid, tartaric acid, malic acid, succinic acid and the chitosan;
Described slow-release material be in ethyl cellulose, hydroxypropyl emthylcellulose, hydroxypropyl cellulose, carboxymethyl cellulose, methylcellulose, Palmic acid and the chitosan any or more than one;
Described pH sensitive material be in polyacrylic acid resin, hydroxyethyl-cellulose acetyl cellulose, cellulose acetate-phthalate ester, cellulose acetate phthalate ester, vinyl acetate phthalate ester, hydroxypropyl methyl cellulose phthalate, Lac and the Hydroxypropyl Methyl Cellulose Phthalate any or more than one;
Described fluidizer is any one or more in magnesium stearate, Pulvis Talci, hydrogenated vegetable oil and the micropowder silica gel;
Described lubricant is any one or more in Pulvis Talci, hydrogenated vegetable oil, sodium stearyl fumarate, magnesium stearate and the stearyl alcohol;
Described binding agent be in water, dehydrated alcohol, water and alcohol mixed solution, Gonak, hydroxypropyl cellulose solution, povidone solution and the carboxymethylcellulose sodium solution any or more than one.
According to above-mentioned Guanfacine Hydrochloride slow releasing preparation, described filler is any one or two kinds of in lactose and the fumaric acid; Described slow-release material is hydroxypropyl emthylcellulose, and the methoxyl group substitute proportion is 15%～40% in the hydroxypropyl emthylcellulose, the hydroxypropyl substitute proportion be the preferred methoxyl group substitute proportion of 3%～15%(about 22%, the hydroxypropyl substitute proportion is about 8%); Described pH sensitive material is the polyacrylic acid resin; Described fluidizer is micropowder silica gel; Described lubricant is any one or two kinds of in magnesium stearate and the sodium stearyl fumarate; Described binding agent is water or water and alcohol mixed solution.
According to above-mentioned Guanfacine Hydrochloride slow releasing preparation, described Guanfacine Hydrochloride slow releasing preparation is by 0.4～3 part of raw material Guanfacine Hydrochloride, 10～40 parts of lactose, 0～20 part of fumaric acid, 10～50 parts of hydroxypropyl emthylcelluloses, 10～40 parts of polyacrylic resins, 0～1 part of micropowder silica gel, 0～1 part of magnesium stearate and 0～10 part of composition of water.
A kind of preparation method of Guanfacine Hydrochloride slow releasing preparation, described preparation method may further comprise the steps:
Supplementary material proportioning according to above-mentioned Guanfacine Hydrochloride slow releasing preparation is prepared various supplementary materials, at first will mix in Guanfacine Hydrochloride, filler and slow-release material or Guanfacine Hydrochloride, filler, slow-release material and the pH sensitive material importing high-speed mixer, obtain uniformed powder behind the mix homogeneously, adopt the high-speed shearing machine shear granulation then, obtain particle diameter less than the granule of 14 eye mesh screens, the gained granule is carried out drying, be dried to gained granule water content and be no more than 5%, select and to obtain Guanfacine Hydrochloride slow releasing preparation granule by the granule of 16 eye mesh screens;
Perhaps prepare various supplementary materials according to the supplementary material proportioning of above-mentioned Guanfacine Hydrochloride slow releasing preparation, at first with Guanfacine Hydrochloride, filler, slow-release material and pH sensitive material import in the high-speed mixer and mix, obtain uniformed powder behind the mix homogeneously, add the binding agent for preparing then, adopt the high-speed shearing machine shear granulation, obtain particle diameter less than the granule of 14 eye mesh screens, the gained granule is carried out drying, be dried to gained granule water content and be no more than 5%, selecting can be by the granule of 16 eye mesh screens, it is even to add the fluidizer and the mix lubricant that prepare then, at last according to the conventional method tabletting, makes the product Guanfacine Hydrochloride slow releasing tablet of all size.
Preparation method according to above-mentioned Guanfacine Hydrochloride slow releasing preparation is characterized in that: the sheet of described product Guanfacine Hydrochloride slow releasing tablet heavily is 100～350mg; The effective dose of Guanfacine Hydrochloride is that the effective dose that 0.5～5mg(is preferably Guanfacine Hydrochloride in the Guanfacine Hydrochloride slow releasing tablet is 1～4mg) in the products obtained therefrom Guanfacine Hydrochloride slow releasing tablet.
Positive beneficial effect of the present invention:
1, utilizes the Guanfacine Hydrochloride slow releasing preparation toxic and side effects of technical solution of the present invention preparation few, be convenient to patient's long-term treatment, and improved the compliance of medication.Take the Guanfacine Hydrochloride slow releasing tablet of technical solution of the present invention preparation, take every day and once can guarantee the 24 hours interior active drug concentration of body, and can reduce the higher nervus centralis side reaction that causes of blood drug level peak value that ordinary preparation brings.The present invention has adopted new recipe and new technology to prepare the Guanfacine Hydrochloride slow releasing preparation simultaneously, has significantly reduced the preparation differences between batches and has improved stability of sample.
2, utilize the Guanfacine Hydrochloride slow releasing preparation of technical solution of the present invention preparation to have the interior sustained release performance of certain hour, what its slow release principle was mainly the present invention's preparation is matrix sustained release tablet, selected adjuvant and preparation method all are easy to get feasible, the suitable suitability for industrialized production that enlarges, the method that adopts has good repeatability.Particularly the present invention preferably fills a prescription and preparation method, be the preferred plan that obtains through screening, select the prescription of optimization for use, adopt the high speed shear granulation, and pressed disc method prepares slow releasing tablet, can realize slow release formulation good release performance in vivo, and the slow releasing tablet that can prepare different size simultaneously adapts to different sufferer crowds.
Below data further specify positive beneficial effect of the present invention by experiment:
The slow releasing tablet of embodiment 1 preparation is adopted in experiment, medicine stability investigation method by the pharmacopeia regulation is investigated (referring to 2010 editions two appendix XI X of Pharmacopoeia of People's Republic of China C), discovery the present invention preferably fills a prescription and has high stability, compares with existing product and prior art to have remarkable result (experimental data sees table 1, table 2 and table 3 for details).
The study on the stability of product Guanfacine Hydrochloride slow releasing preparation of the present invention under table 1 hot conditions
The study on the stability of product Guanfacine Hydrochloride slow releasing preparation of the present invention under table 2 super-humid conditions
The study on the stability of product Guanfacine Hydrochloride slow releasing preparation of the present invention under the table 3 strong illumination condition
In above-mentioned about release experiment condition of the present invention:
Leaching condition: the device of dissolution first method, rotating speed are 100rpm, and temperature is 37 ℃, and release medium is the hydrochloride buffer of 900ml, pH 2.2, and detection method is high performance liquid chromatography.
3, product Guanfacine Hydrochloride slow releasing tablet of the present invention, preparation process is simple for process, adopt the high speed shear granulating process, meet the requirement of big production, under laboratory scale, can finish the amplification production of 10000～30000 units, the production efficiency height can prepare the Guanfacine Hydrochloride slow releasing tablet of 1～4mg different size.
4, product Guanfacine Hydrochloride slow releasing preparation of the present invention, show for dynamics research through the body giving drugs into nose, has the bioavailability equivalence with ordinary preparation, do not produce the problem that reduces bioavailability because of slow releasing function, it discharges model and has reduced blood plasma Chinese medicine peak concentration, reduce the possibility that has side effects, take the compliance that has improved patient's medication once a day.
5, product Guanfacine Hydrochloride slow releasing preparation of the present invention is investigated through accelerated stability test, in 6 months stable, the medicament contg of character, related substance all in controlled range, suitability for industrialized production.
Four, description of drawings:
The release in vitro degree that Fig. 1 embodiment of the invention 1 gained Guanfacine Hydrochloride slow releasing preparation is three batches.
Five, the specific embodiment:
Further set forth the present invention below in conjunction with embodiment, but do not limit content of the present invention.
Embodiment 1:
The supplementary material of Guanfacine Hydrochloride slow releasing preparation of the present invention consists of:
Be unit with g, the shared weight portion of each supplementary material in the Guanfacine Hydrochloride slow releasing preparation original formulation has been enlarged 5～15 times, and the supplementary material of Guanfacine Hydrochloride slow releasing tablet consists of Guanfacine Hydrochloride 11.48g, lactose 232.5g, fumaric acid 75g, hydroxypropyl emthylcellulose 250g, polyacrylic resin 175g, micropowder silica gel 3g, magnesium stearate 3g and 120g water.
The preparation method of Guanfacine Hydrochloride slow releasing preparation of the present invention:
Form the various supplementary materials of preparation according to the supplementary material of above-mentioned Guanfacine Hydrochloride slow releasing tablet, with the Guanfacine Hydrochloride 11.48g for preparing, lactose 232.5g, fumaric acid 75g, hydroxypropyl emthylcellulose 250g, polyacrylic resin 175g pulverizes, be crushed to by after in high-speed mixer, mixing 30 minutes behind 80 eye mesh screens, obtain uniformed powder, adopt high-speed shearing machine under the high speed shear state, slowly to add binding agent water 120g the gained uniformed powder, high speed shear is granulated, the gained granule was put into 60 ℃ of convection oven dry 2 hours, carry out uniformity of dosage units and water content inspection (dry back granule moisture content is no more than 5%), after qualified the gained granule is passed through 16 eye mesh screen granulate, add fluidizer micropowder silica gel 3g and the magnesium stearate lubricant 3g for preparing behind the granulate, utilize mixer to continue to be mixed to mix homogeneously, at last according to the conventional method tabletting, namely get the Guanfacine Hydrochloride slow releasing tablet (with reference to 2010 editions two appendix X D of Chinese Pharmacopoeia and appendix X E, every batch of testing product uniformity of dosage units and release, in the lucifuge of packing into after the qualified hermetic container, get product.）。
Embodiment 2: substantially the same manner as Example 1, difference is:
The supplementary material of Guanfacine Hydrochloride slow releasing preparation of the present invention consists of:
Be unit with g, the shared weight portion of each supplementary material in the Guanfacine Hydrochloride slow releasing preparation original formulation has been enlarged 5～15 times, and the supplementary material of Guanfacine Hydrochloride slow releasing tablet consists of Guanfacine Hydrochloride 5.74g, mannitol 190g, citric acid 100g, hydroxypropyl cellulose 300g, polyacrylic resin 135g, micropowder silica gel 3g, sodium stearyl fumarate 5g and 5% polyvidone aqueous solution 100g.
Embodiment 3: substantially the same manner as Example 1, difference is:
Be unit with g, the shared weight portion of each supplementary material in the Guanfacine Hydrochloride slow releasing preparation original formulation has been enlarged 5～15 times, and the supplementary material of Guanfacine Hydrochloride slow releasing tablet consists of Guanfacine Hydrochloride 11.48g, lactose 200g, microcrystalline Cellulose 30g, fumaric acid 100g, ethyl cellulose 250g, polyacrylic resin 150g, micropowder silica gel 3g, magnesium stearate 3g and water 120g..
Be specimen with prepared Guanfacine Hydrochloride slow releasing tablet among the embodiment 1, the release experimental technique is as follows:
Get embodiment 1 products obtained therefrom, according to drug release determination method (2010 editions two appendix X D of Chinese Pharmacopoeia, second method), adopt the dissolution determination subtraction unit, rotating speed is 100rpm, and temperature is 37 ℃, and release medium is the hydrochloride buffer 900ml of pH 2.2, sampling time point is: 1 hour, 4 hours, 8 hours and 24 hours, it is an amount of to get solution at each time point, filters, and gets subsequent filtrate as need testing solution.Get contrast solution and the need testing solution of concentration known, inject high performance liquid chromatograph respectively, the record chromatogram calculates different burst sizes constantly by external standard method.
Experimental result is seen the accompanying drawing 1 in the description of drawings, and embodiment 2,3 is under identical test condition, and experimental result is identical with embodiment 1, all meets the requirements.
Embodiment 4: substantially the same manner as Example 1, difference is:
Be unit with g, the shared weight portion of each supplementary material in the Guanfacine Hydrochloride slow releasing preparation original formulation has been enlarged 5～15 times, and the supplementary material of Guanfacine Hydrochloride slow releasing tablet consists of Guanfacine Hydrochloride 11.48g, sucrose 175g, tartaric acid 50g, hydroxypropyl cellulose 200g, methylcellulose 115g, cellulose acetate phthalate ester 100g, vinyl acetate phthalate ester 47g, Pulvis Talci 5.25g, hydrogenated vegetable oil 5.25g and 50% ethanol water mixed solution 150g.
Embodiment 5: substantially the same manner as Example 1, difference is:
Be unit with g, the shared weight portion of each supplementary material in the Guanfacine Hydrochloride slow releasing preparation original formulation has been enlarged 5～15 times, and the supplementary material of Guanfacine Hydrochloride slow releasing tablet consists of Guanfacine Hydrochloride 22.5g, starch 175g, Sargassum polysaccharides 100g, fumaric acid 62.5g, hydroxypropyl emthylcellulose 70g, carboxymethyl cellulose 50g, methylcellulose 30g, polyacrylic acid resin 120g, hydroxyethyl-cellulose acetyl cellulose 75g, hydrogenated vegetable oil 6.0g, Pulvis Talci 6.0g and 80% ethanol water mixed liquid 150g.
Embodiment 6: substantially the same manner as Example 1, difference is:
Be unit with g, the shared weight portion of each supplementary material in the Guanfacine Hydrochloride slow releasing preparation original formulation has been enlarged 5～20 times, and the supplementary material of Guanfacine Hydrochloride slow releasing tablet consists of Guanfacine Hydrochloride 11.25g, malic acid 120g, succinic acid 67.5g, hydroxypropyl emthylcellulose 200g, carboxymethyl cellulose 137.5g, polyacrylic acid resin 120g, Hydroxypropyl Methyl Cellulose Phthalate 30g, micropowder silica gel 7.5g, magnesium stearate 7.5g and 95% ethanol water mixed liquid mixed liquor 180g.
Be specimen with prepared Guanfacine Hydrochloride slow releasing tablet among the embodiment 1, the release experimental technique is as follows:
Get embodiment 1 products obtained therefrom, according to drug release determination method (2010 editions two appendix X D of Chinese Pharmacopoeia, second method), adopt the dissolution determination subtraction unit, rotating speed is 100rpm, and temperature is 37 ℃, and release medium is the hydrochloride buffer 900ml of pH 2.2, sampling time point is: 1 hour, 4 hours, 8 hours and 24 hours, it is an amount of to get solution at each time point, filters, and gets subsequent filtrate as need testing solution.Get contrast solution and the need testing solution of concentration known, inject high performance liquid chromatograph respectively, the record chromatogram calculates different burst sizes constantly by external standard method.
Experimental result is seen the accompanying drawing 1 in the description of drawings, and the products obtained therefrom of embodiment 2～6 is under identical test condition, and experimental result is identical with embodiment 1, all meets the requirements.
Embodiment 7:
The supplementary material of Guanfacine Hydrochloride slow releasing preparation of the present invention consists of:
Be unit with g, the shared weight portion of each supplementary material in the Guanfacine Hydrochloride slow releasing preparation original formulation has been enlarged 5～15 times, and the supplementary material of Guanfacine Hydrochloride slow releasing tablet consists of Guanfacine Hydrochloride 12.0g, lactose 200g, fumaric acid 100g, hydroxypropyl emthylcellulose 260g and polyacrylic resin 110g.
The preparation method of Guanfacine Hydrochloride slow releasing preparation of the present invention:
Supplementary material proportioning according to above-mentioned Guanfacine Hydrochloride slow releasing preparation is prepared various supplementary materials, at first with Guanfacine Hydrochloride, filler (lactose and fumaric acid), slow-release material (hydroxypropyl emthylcellulose) and pH sensitive material (polyacrylic resin) import in the high-speed mixer and mix, obtain uniformed powder behind the mix homogeneously, adopt the high-speed shearing machine shear granulation then, obtain particle diameter less than the granule of 14 eye mesh screens, the gained granule is carried out drying, be dried to gained granule water content and be no more than 5%, select and to obtain Guanfacine Hydrochloride slow releasing preparation granule by the granule of 16 eye mesh screens.
Embodiment 8: substantially the same manner as Example 7, difference is:
The supplementary material of Guanfacine Hydrochloride slow releasing preparation of the present invention consists of:
Be unit with g, the shared weight portion of each supplementary material in the Guanfacine Hydrochloride slow releasing preparation original formulation has been enlarged 5～15 times, and the supplementary material of Guanfacine Hydrochloride slow releasing tablet consists of Guanfacine Hydrochloride 5.6g, lactose 234g, hydroxypropyl emthylcellulose 234g and polyacrylic resin 196g.
Embodiment 9: substantially the same manner as Example 7, difference is:
The supplementary material of Guanfacine Hydrochloride slow releasing preparation of the present invention consists of:
Be unit with g, the shared weight portion of each supplementary material in the Guanfacine Hydrochloride slow releasing preparation original formulation has been enlarged 5～15 times, and the supplementary material of Guanfacine Hydrochloride slow releasing tablet consists of Guanfacine Hydrochloride 20.5g, fumaric acid 168g, hydroxypropyl emthylcellulose 300g and polyacrylic resin 180g.
Embodiment 10:
The supplementary material of Guanfacine Hydrochloride slow releasing preparation of the present invention consists of:
Be unit with g, the shared weight portion of each supplementary material in the Guanfacine Hydrochloride slow releasing preparation original formulation has been enlarged 5～15 times, the supplementary material of Guanfacine Hydrochloride slow releasing tablet consists of Guanfacine Hydrochloride 5.0g, fumaric acid 320g and hydroxypropyl emthylcellulose 280g.
The preparation method of Guanfacine Hydrochloride slow releasing preparation of the present invention:
Supplementary material proportioning according to above-mentioned Guanfacine Hydrochloride slow releasing preparation is prepared various supplementary materials, at first Guanfacine Hydrochloride, filler (fumaric acid) and slow-release material (hydroxypropyl emthylcellulose) are imported in the high-speed mixer and mix, obtain uniformed powder behind the mix homogeneously, adopt the high-speed shearing machine shear granulation then, obtain particle diameter less than the granule of 14 eye mesh screens, the gained granule is carried out drying, be dried to gained granule water content and be no more than 5%, select and to obtain Guanfacine Hydrochloride slow releasing preparation granule by the granule of 16 eye mesh screens.
Embodiment 11: substantially the same manner as Example 10, difference is:
The supplementary material of Guanfacine Hydrochloride slow releasing preparation of the present invention consists of:
Be unit with g, the shared weight portion of each supplementary material in the Guanfacine Hydrochloride slow releasing preparation original formulation has been enlarged 5～15 times, the supplementary material of Guanfacine Hydrochloride slow releasing tablet consists of Guanfacine Hydrochloride 11.5g, lactose 300g and hydroxypropyl emthylcellulose 260g.
Claims (1)
1. Guanfacine Hydrochloride slow releasing preparation, it is characterized in that: described Guanfacine Hydrochloride slow releasing preparation is by 0.4～3 part of raw material Guanfacine Hydrochloride, 10～40 parts of lactose, 0～20 part of fumaric acid, 10～50 parts of hydroxypropyl emthylcelluloses, 10～40 parts of polyacrylic resins, 0～1 part of micropowder silica gel, 0～1 part of magnesium stearate and 0～10 part of composition of water.
2, the preparation method of the described Guanfacine Hydrochloride slow releasing preparation of a kind of claim 1 is characterized in that, described preparation method is:
Supplementary material proportioning according to the described Guanfacine Hydrochloride slow releasing preparation of claim 1 is prepared various supplementary materials, at first with Guanfacine Hydrochloride, the filler lactose, fumaric acid and slow-release material hydroxypropyl emthylcellulose, pH sensitive material polyacrylic resin imports in the high-speed mixer and mixes, obtain uniformed powder behind the mix homogeneously, add the binding agent water for preparing then, adopt the high-speed shearing machine shear granulation, obtain particle diameter less than the granule of 14 eye mesh screens, the gained granule is carried out drying, be dried to gained granule water content and be no more than 5%, selecting can be by the granule of 16 eye mesh screens, add fluidizer micropowder silica gel and the magnesium stearate lubricant mix homogeneously for preparing then, according to the conventional method tabletting, make the product Guanfacine Hydrochloride slow releasing tablet of all size at last.
3, the preparation method of Guanfacine Hydrochloride slow releasing preparation according to claim 2 is characterized in that: the sheet of described product Guanfacine Hydrochloride slow releasing tablet heavily is 100～350mg; The effective dose of Guanfacine Hydrochloride is 0.5～5mg in the products obtained therefrom Guanfacine Hydrochloride slow releasing tablet.
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| CN103705480B (en) * | 2013-12-31 | 2015-09-30 | 郑州大明药物科技有限公司 | Guanidine hydrochloride sustained release and preparation method thereof |
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| CN104473906A (en) * | 2014-11-21 | 2015-04-01 | 哈尔滨圣吉药业股份有限公司 | Guanfacine hydrochloride sustained release pellets and preparation method thereof |
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| CN108042502A (en) * | 2017-12-05 | 2018-05-18 | 浙江华海药业股份有限公司 | A kind of guanfacine hydrochloride sustained release tablets and preparation method thereof |
| WO2020047198A1 (en) | 2018-08-31 | 2020-03-05 | Incyte Corporation | Salts of an lsd1 inhibitor and processes for preparing the same |
| CN113648285B (en) * | 2021-07-15 | 2022-11-11 | 南京海纳医药科技股份有限公司 | Guanfacine hydrochloride membrane controlled-release tablet and preparation method thereof |
| EP4292586A1 (en) * | 2022-06-15 | 2023-12-20 | Sawai Pharmaceutical Co., Ltd. | Guanfacine hydrochloride containing pharmaceutical preparation |
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| CN101252917A (en) * | 2005-07-28 | 2008-08-27 | 夏尔有限责任公司 | Pharmaceutical formulations/composition of guanfacine suitable for single dose form administration daily |
| CN101588794A (en) * | 2007-01-25 | 2009-11-25 | 万能药生物有限公司 | Modified release pharmaceutical composition and a process of making the same |
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| CN102579381A (en) | 2012-07-18 |
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