CN105708796A - Sustained release preparation containing trazodone hydrochloride oral solution and preparation method of sustained release preparation - Google Patents
Sustained release preparation containing trazodone hydrochloride oral solution and preparation method of sustained release preparation Download PDFInfo
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- CN105708796A CN105708796A CN201610176071.6A CN201610176071A CN105708796A CN 105708796 A CN105708796 A CN 105708796A CN 201610176071 A CN201610176071 A CN 201610176071A CN 105708796 A CN105708796 A CN 105708796A
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- resin
- trazodone
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- oral administration
- slow releasing
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- 238000002360 preparation method Methods 0.000 title claims abstract description 44
- 229960002301 trazodone hydrochloride Drugs 0.000 title claims abstract description 39
- OHHDIOKRWWOXMT-UHFFFAOYSA-N trazodone hydrochloride Chemical compound [H+].[Cl-].ClC1=CC=CC(N2CCN(CCCN3C(N4C=CC=CC4=N3)=O)CC2)=C1 OHHDIOKRWWOXMT-UHFFFAOYSA-N 0.000 title claims abstract description 35
- 239000003405 delayed action preparation Substances 0.000 title abstract description 6
- 229940100688 oral solution Drugs 0.000 title abstract 5
- 239000011347 resin Substances 0.000 claims abstract description 46
- 229920005989 resin Polymers 0.000 claims abstract description 46
- 239000003814 drug Substances 0.000 claims abstract description 36
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 claims abstract description 29
- 229920000642 polymer Polymers 0.000 claims abstract description 28
- 239000003094 microcapsule Substances 0.000 claims abstract description 26
- 239000003456 ion exchange resin Substances 0.000 claims abstract description 20
- 229920003303 ion-exchange polymer Polymers 0.000 claims abstract description 20
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- 238000000576 coating method Methods 0.000 claims abstract description 17
- 239000000463 material Substances 0.000 claims abstract description 15
- 239000000243 solution Substances 0.000 claims description 47
- PHLBKPHSAVXXEF-UHFFFAOYSA-N trazodone Chemical compound ClC1=CC=CC(N2CCN(CCCN3C(N4C=CC=CC4=N3)=O)CC2)=C1 PHLBKPHSAVXXEF-UHFFFAOYSA-N 0.000 claims description 29
- 229960003991 trazodone Drugs 0.000 claims description 28
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- 238000000034 method Methods 0.000 claims description 25
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- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 6
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- QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical compound [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 claims description 2
- QPCDCPDFJACHGM-UHFFFAOYSA-N N,N-bis{2-[bis(carboxymethyl)amino]ethyl}glycine Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(=O)O)CCN(CC(O)=O)CC(O)=O QPCDCPDFJACHGM-UHFFFAOYSA-N 0.000 claims description 2
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- PNVNVHUZROJLTJ-UHFFFAOYSA-N venlafaxine Chemical compound C1=CC(OC)=CC=C1C(CN(C)C)C1(O)CCCCC1 PNVNVHUZROJLTJ-UHFFFAOYSA-N 0.000 description 1
Classifications
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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
- A61K9/10—Dispersions; Emulsions
-
- 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
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
-
- 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
-
- 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/5021—Organic macromolecular compounds
- A61K9/5026—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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/5021—Organic macromolecular compounds
- A61K9/5036—Polysaccharides, e.g. gums, alginate; Cyclodextrin
- A61K9/5042—Cellulose; Cellulose derivatives, e.g. phthalate or acetate succinate esters of hydroxypropyl methylcellulose
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Dispersion Chemistry (AREA)
- Inorganic Chemistry (AREA)
- Nutrition Science (AREA)
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- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a sustained release preparation containing a trazodone hydrochloride oral solution and a preparation method of the sustained release preparation. The sustained release preparation is a suspended type oral solution which is slowly released within 24 hours. The suspended oral solution contains a solution and medicine resin coating micro-capsules. The medicine resin coating micro-capsules are made from a medicine resin polymer containing deprementia type medicine and ion exchange resin and a sustained release material on the outer layer of the medicine resin polymer. By means of the preparation, medicine can be slowly released into bodies, the aims of the stable blood medicine concentration and the long efficacy time duration are achieved, a patient only needs to take the preparation once every day to achieve the treatment effect, and the preparation prepared into the suspended type oral solution can be conveniently and easily swallowed by the patient.
Description
Technical field
The present invention relates to field of medicaments, in particular the slow releasing preparation of a kind of hydrochloric trazodone oral administration solution and the method for preparing this hydrochloric trazodone oral administration solution.
Background technology
Depression is a kind of prevalence height, serious harm human physical and mental health, has the mental sickness of high suicide risk, low for principal character with notable and lasting mental state, caused by the many factors such as biological, social, psychological.Due to accelerating and strong competitive pressure of modern society's rhythm of life, cause depression rate to increase year by year and age of onset rejuvenation increasingly, become the commonly encountered diseases of harm human physical and mental health.
Trazodone hydrochloride is a kind of atypical tetracyclic antidepressants, and it can block the heavily absorption of 5-HT (5-hydroxy tryptamine), and its metabolite has again the effect of antagonism 5-HT, thus producing antidepressant effect.H1 receptor and α 1 adrenoreceptor is blocked, thus producing significantly calm and syngignoscism due to its property of can select that.
The trazodone hydrochloride preparation of current domestic commercial type, it is conventional tablet (50mg or 100mg/ sheet, daily dose is 50-200mg), within average one day, needs are administered 2-3 time, and still at clinical stage in the current importer of trazodone hydrochloride slow releasing tablet, this slow releasing tablet is to be researched and developed by AngeliniLabopharm company and list in the U.S. in February, 2010, and commodity are called Oleptro, and listing specification has 150mg and 300mg.There is the side effect such as drowsiness, blurred vision, perspiration, myalgia, gastrointestinal reaction due to trazodone hydrochloride, therefore slow releasing preparation has very big advantage, its relatively stable release concentration greatly alleviates the intensity of above-mentioned side effect, and takes medicine conveniently, within one day, takes medicine once.
CN101252932 provides trazodone hydrochloride slow releasing tablet (Oleptro) prescription and the preparation technology of U.S.'s listing, adopts excipient hydroxypropyl two to form sediment the materials such as acid powder phosphide (trade name Contramid) and binding agent hypromellose to control the release of medicine.The hydroxypropyl two that it uses form sediment acid the powder phosphide domestic other adjuvant of pharmaceutical grade that there is no at present can use.Simultaneously relatively large by the slow releasing tablet daughter type obtained by its formulation and technology, it is unfavorable for that child and old man swallow use.
CN102935074A provides the preparation method of a kind of trazodone hydrochloride osmotic pump controlled release tablet disclosed in Chengdu Kanghong Medicine Group Co.ltd, its controlled release tablet comprises tablet core, semipermeable membrane coating and drug release hole three part composition, its preparation technology is higher to outfit and the performance requirement of equipment, simultaneously the degree of accuracy of its technological requirement to industrialization to realize difficulty relatively big, simultaneously because of its for oral solid formulation equally to having the old of dysphagia and swallowing of child patient to take certain inconvenience.
Therefore, prior art existing defects, it is necessary to improve.
Summary of the invention
The technical problem to be solved is: the trazodone hydrochloride liquid slow-release preparation providing be administered once for a kind of a day, and patient only need to take and once can reach therapeutic effect every day, swallows the convenient slow releasing preparation being easy to hydrochloric trazodone oral administration solution.
Technical scheme is as follows: the slow releasing preparation of a kind of hydrochloric trazodone oral administration solution, it for realizing the suspension type oral administration solution of slow releasing in 24h, suspension type oral administration solution includes solution and medical resin dressing microcapsule, and medical resin dressing microcapsule includes the slow-release material of the medical resin polymer containing spirit depressing class medicine and ion exchange resin and medical resin polymeric outer layer.
Being applied to technique scheme, in described slow releasing preparation, spirit depressing class medicine is trazodone hydrochloride, and medical resin polymer is trazodone resinous polymer.
Being applied to each technique scheme, in described slow releasing preparation, ion exchange resin is acid cation exchange resin.
Being applied to each technique scheme, in described slow releasing preparation, ion exchange resin is that particle diameter pulverizes requirement by more than 250 mesh sieves, and particle diameter is the ion exchange resin of 0.1-60 micron；Or, it is preferable that ion exchange resin is that particle diameter pulverizes requirement by more than 150 mesh sieves, and particle diameter is at the ion exchange resin of 0.1-100 micron.
Being applied to each technique scheme, in described slow releasing preparation, the particle diameter of medical resin dressing microcapsule is 0.1-150 micron, and, medical resin dressing microcapsule is 20%-60% at the content of suspension type oral administration solution.
Being applied to each technique scheme, in described slow releasing preparation, described slow-release material is the slow-release material comprising polyacrylic resin class or ethyl cellulose type.
It is applied to each technique scheme, in described slow releasing preparation, in suspension type oral administration solution, its solvent adopted is deionized water, and the suspending agent of employing is be combined with the arabic gum of one or more in hypromellose class or carboxymethyl cellulose class or sodium alginate or carbomer series or xanthan gum；The flavoring agent adopted is sorbitol or fructose class；The ion chelating agent adopted is ethylenediaminetetraacetic acid, disodiumedetate, a kind of or arbitrarily several mixture in disodiumedetate, diethyl pentetic acid disodium；The acidity regulator adopted is hydrochloric acid or citric acid buffer salt or phosphoric acid buffer salt；The preservative adopted is parabens.
It is applied to each technique scheme, a kind of method of slow releasing preparation preparing any of the above-described described hydrochloric trazodone oral administration solution, A: adopt trazodone hydrochloride and resin ion to carry out ion-exchange step, obtain trazodone resinous polymer；B: adopt the slow-release material comprising polyacrylic resin or ethyl cellulose that trazodone resinous polymer is carried out coating, obtain trazodone resin dressing microcapsule；C: adopt deionized water and trazodone resin dressing microcapsule, prepares suspension type oral administration solution.
Being applied to each technique scheme, in described method, in step B, trazodone resin dressing microcapsule is to adopt heat drying or heating evacuation or lyophilization step to make.
It is applied to each technique scheme, in described method, also includes step D: using brown polyester bottles or vial additional shading carton that suspension type oral administration solution is packed, the medicine liquid volume of each minimum package is 5～500ml.
Adopt such scheme, according to the former slow releasing tablet In Vitro Dissolution data when same media and dissolving-out method of grinding, the vitro release of trazodone hydrochloride provided by the invention determines that this product 1h release is not more than 30%, 6h is accumulative is released in 30-55%, the accumulative release of 12h is less than 80%, and the accumulative release of 24h should be not less than 80%.Being thus able to make medicine slow releasing enter internal, reach blood drug level steady, the purpose of duration of efficacy length, patient only need to take every day once can reach therapeutic effect, adopts the preparation making suspension type oral administration solution, and patient swallows convenient easy.
Accompanying drawing explanation
Fig. 1 is the former slow releasing tablet of grinding of existing specification 150mg and 300mg, and tests 1 in embodiment and test the trazodone hydrochloride slow suspension type oral administration solution releasing curve diagram at the same terms of 2 preparations.
Detailed description of the invention
Below in conjunction with the drawings and specific embodiments, the present invention is described in detail.
Present embodiments provide the slow releasing preparation of a kind of hydrochloric trazodone oral administration solution, the present embodiment is for the deficiency of existing listing preparation, basis lists slow releasing preparation one consumption per day and primarily determines that the hydrochloric trazodone consumption of taking dose is 150mg and 300mg/ sky simultaneously, to guarantee the effectiveness of novel formulation.Physicochemical property further according to trazodone hydrochloride carries out substantial amounts of preparation research, completes the development work of the sustained release liquid suspensoid that is administered once one.
The oral liquid sustained-release preparation of hydrochloric trazodone, it is dissolved in trazodone hydrochloride in distilled water or deionized water and dissolves completely, concentration is at 0.1～22mg/ml, wherein, preferred concentration is about 20mg/ml, select to pulverize the ion exchange resin of more than 200 orders, wherein, preferably pulverized the ion exchange resin of more than 300 orders, the preferred storng-acid cation exchange resin of ion exchange resin, it is heated by the amount input ion exchange resin that trazodone hydrochloride/ion exchange resin weight ratio is 1:0.5～1:3 and is sufficiently stirred for and carry out ion exchange, wherein, the weight ratio of preferred trazodone hydrochloride/ion exchange resin is 1:0.9, preferred heating maintains the temperature at 50 ± 5 DEG C, finally, gained trazodone hydrochloride ion exchange resin may select the mode of heating, drying or employing heating evacuation or lyophilizing on evaporator and removes moisture, finally prepare trazodone hydrochloride resinous polymer.
Control the moisture of trazodone hydrochloride resinous polymer 0.1～6%, wherein, preferably control the moisture of trazodone hydrochloride resinous polymer at 0.5-3%, trazodone hydrochloride ketone resin dressing microcapsule content controls between 20-65%, preferably, trazodone hydrochloride ketone resin dressing microcapsule content controls 45 ± 10%.The particle diameter of trazodone hydrochloride ketone resin dressing microcapsule should be not more than 100um.
Gained trazodone hydrochloride resinous polymer is to adopt 95% alcoholic solution containing polyacrylic resin or the slow-release material of ethyl cellulose to carry out coating, wherein the optional model of polyacrylic resin includes polyacrylic resin II, polyacrylic resin III, polyacrylic resin IV, also includes adoptingThe material of series carries out coating, and coating mode can adopt spray drying method or air suspension coating.Wherein spray drying method is directly to be scattered in by medical resin in the alcoholic solution of acrylic resin or ethyl cellulose, alcoholic solution can add appropriate plasticizer, antiplastering aid and defoamer, the thermal current of inertia is atomized, dries, the solvent making dissolving capsule material evaporates rapidly, by trazodone hydrochloride resinous polymer encapsulation, obtain the free-pouring dried powder of almost spherical.
Medicine carrying resinous polymer is then suspended in fluidising chamber first with vertical air blast by air suspension coating, the alcoholic solution of acrylic resin or ethyl cellulose plasticizer-containing is sprayed and invests resin surface, wherein, alcoholic solution can add appropriate plasticizer, antiplastering aid and defoamer, solvent is quickly evaporated by thermal current, slow-release material capsule material deposits film forming on medical resin surface, is drying to obtain trazodone hydrochloride ketone resin microcapsule at 45 ± 5 DEG C of temperature.Above two method need to control ethanol residual limit, and finally controls ethanol residual less than 0.2%.The dressing microcapsule content measuring trazodone hydrochloride resinous polymer should 18～65%.
Finally prepare suspension type oral administration solution:
In a certain amount of deionized water of container, add appropriate Tween 80 and polysorbate or fructose makes it dissolve, add appropriate medical resin polymer coating microcapsule, be sufficiently impregnated with, standby.
In the deionized water that container two is quantitative add metal-chelator stirring and dissolving, add antibacterial stirring or heating make it fully dissolve or disperse, finally add suspending agent and make it fully swelling, standby.
Adding acidity regulator in the deionized water that container is three kinds quantitative, stirring makes it fully dissolve, standby.
Solution in container one is slowly added in container two and stirs, then solution in container three is slowly added in container two, control medicinal liquid final pH 3.0～5.0, measure sedimentation volume ratio after shaking up, requirement should be met, thus preparing suspension type oral administration solution.
In Vitro Dissolution test is the important means that technique determined by screening prescription, and the quality control important role to preparation.The present embodiment adopts the 900ml0.15mol/lNaCl of degassed process to be release medium rotating speed 50r/min, temperature 37 DEG C.According to 2015 editions four 0931 the second method (paddle method) operations of Chinese Pharmacopoeia, respectively at 1,2,3,6,8,12,24h samples 10ml, filters through 0.45 μm of microporous filter membrane, discards just filtrate, take subsequent filtrate standby, add synthermal in time, the respective media of same volume, subsequent filtrate is measured in 311nm place absorbance, different time sample liquid concentration is calculated according to standard curve, investigating the Cumulative release amount of 24 hours and the relation of time, wherein, the release data of the former experiment 1 grinding slow releasing tablet 150mg and 300mg and the present embodiment and experiment 2 are as shown in Table 1.
According to the former slow releasing tablet In Vitro Dissolution data when same media and dissolving-out method of grinding, the vitro release of the trazodone hydrochloride of the present embodiment confession determines that this product 1h release is not more than 30%, 6h is accumulative is released in 30-55%, the accumulative release of 12h is less than 80%, and the accumulative release of 24h should be not less than 80%.It is thus able to make medicine slow releasing enter internal, reaches blood drug level steady, the purpose of duration of efficacy length.
The trazodone hydrochloride slow releasing preparation made according to the present invention has been carried out high temperature, high humidity, illumination experiment, and result shows that this product is under high temperature, high humidity, illumination, condition, and stability is better.
Experiment 1:
The preparation of trazodone resinous polymer: first polyvinylbenzenesulfonic acid cation exchange resin AMBERLITEIRP69 was pulverized 300 mesh sieves, trazodone hydrochloride/polyvinylbenzenesulfonic acid cation exchange resin AMBERLITEIRP69 presses the amount of 0.9:1 weight ratio, trazodone hydrochloride is added the deionized water of appropriate (calculate by principal agent concentration of ordinary dissolution 20mg/ml and add water), stirring and dissolving, under agitation add the mixing of AMBERLITEIRP69 cation exchange resin, timing sampling, measures the concentration of drug in solution.When drug level no longer time to time change and balance to be achieved, it is not associated with medicine with what deionized water washed away resin surface, is drying to obtain medicine carrying resin at 40 DEG C-60 DEG C.
The coating of trazodone resinous polymer: above-mentioned dry medicine carrying resin is added in the ethyl cellulose 95% alcoholic solution containing pEG4000 and pEG400 plasticizer (ethyl cellulose concentration about: 4%), stir, medical resin suspension is pumped into coating in spray dryer, obtains medical resin sustained-release microparticle.Inlet temperature controls at 45 ± 5 DEG C.Prepare trazodone hydrochloride resinous polymer dressing microcapsule, measure its drug content and be about 38.68%.
The preparation of suspension type oral administration solution: a certain amount of toward container, adds appropriate Tween 80 and polysorbate slight fever makes it dissolve, add appropriate medical resin polymer coating microcapsule, be sufficiently impregnated with in the deionized water of the water yield of about 50%, standby.
Quantitative toward container two.In the deionized water of the water yield of about 40% add metal-chelator stirring and dissolving, add antibacterial stirring or heating make it fully dissolve or disperse, finally add suspending agent and make it fully swelling, standby.
Quantitative toward three kinds of container, the deionized water of the water yield of about 10% adds acidity regulator, stirring makes it fully dissolve, standby.
Solution in container one is slowly added in container two and stirs, then solution in container three is slowly added in container two, control medicinal liquid final pH 3.0～5.0, measure sedimentation volume ratio after shaking up, should meet the requirements, finally obtain suspension type oral administration solution.
Experiment 2:
The preparation of trazodone resinous polymer: first polyvinylbenzenesulfonic acid cation exchange resin AMBERLITEIRP69 was pulverized 300 mesh sieves, trazodone hydrochloride/polyvinylbenzenesulfonic acid cation exchange resin AMBERLITEIRP69 presses the amount of 1:0.9 weight ratio, trazodone hydrochloride is added the deionized water of appropriate (calculate by principal agent concentration of ordinary dissolution 20mg/ml and add water), stirring and dissolving, under agitation add the mixing of AMBERLITEIRP69 cation exchange resin, timing sampling, measures the concentration of drug in solution.When drug level no longer time to time change and balance to be achieved, it is not associated with medicine with what deionized water washed away resin surface, is drying to obtain medicine carrying resin at 40 DEG C-60 DEG C.
The coating of trazodone resinous polymer: above-mentioned dry medicine carrying resin is added in the ethyl cellulose 95% alcoholic solution (ethyl cellulose concentration about 8%) containing pEG4000 and pEG400 plasticizer, stir, medical resin suspension is pumped into coating in spray dryer, obtains medical resin sustained-release microparticle.Inlet temperature controls at 45 ± 5 DEG C.Prepare trazodone hydrochloride resinous polymer dressing microcapsule, measure its drug content and be about 43.56%.
The preparation of suspendible oral administration solution: a certain amount of toward container, adds appropriate Tween 80 and polysorbate slight fever makes it dissolve, add appropriate medical resin polymer coating microcapsule, be sufficiently impregnated with in the deionized water of the water yield of about 50%, standby.
Toward container two quantitatively, the water yield of about 40%, deionized water in add metal-chelator stirring and dissolving, add antibacterial stirring or heating makes it fully dissolve or disperse, finally add suspending agent and make it fully swelling, standby.
Quantitative toward three kinds of container, the deionized water of the water yield of about 10% adds acidity regulator, stirring makes it fully dissolve, standby.
Solution in container one is slowly added in container two and stirs, then solution in container three is slowly added in container two, control medicinal liquid final pH 3.0～5.0, measure sedimentation volume ratio after shaking up, should meet the requirements, finally obtain suspension type oral administration solution.
150mg and 300mg trazodone hydrochloride slow releasing tablet is had for the specification that existing AngeliniLabopharm company researchs and develops with following table one, and the present embodiment is tested the release tables of data of the slow suspension type oral administration solutions of trazodone hydrochlorides of 1 and experiment 2 preparation, its releasing curve diagram as shown in Figure 1:
Table one:
These are only presently preferred embodiments of the present invention, be not limited to the present invention, all any amendment, equivalent replacement and improvement etc. made within the spirit and principles in the present invention, should be included within protection scope of the present invention.
Claims (10)
1. the slow releasing preparation of a hydrochloric trazodone oral administration solution, it is characterised in that
It for realizing the suspension type oral administration solution of slow releasing in 24h, suspension type oral administration solution includes solution and medical resin dressing microcapsule, and medical resin dressing microcapsule includes the slow-release material of the medical resin polymer containing spirit depressing class medicine and ion exchange resin and medical resin polymeric outer layer.
2. slow releasing preparation according to claim 1, it is characterised in that: spirit depressing class medicine is trazodone hydrochloride, and medical resin polymer is trazodone resinous polymer.
3. slow releasing preparation according to claim 1, it is characterised in that: ion exchange resin is acid cation exchange resin.
4. slow releasing preparation according to claim 3, it is characterised in that: ion exchange resin is that particle diameter is pulverized and required by more than 250 mesh sieves, and particle diameter is the ion exchange resin of 0.1-60 micron；Or, it is preferable that ion exchange resin is that particle diameter pulverizes requirement by more than 150 mesh sieves, and particle diameter is at the ion exchange resin of 0.1-100 micron.
5. slow releasing preparation according to claim 1, it is characterised in that: the particle diameter of medical resin dressing microcapsule is 0.1-150 micron, and, medical resin dressing microcapsule is 20%-60% at the content of suspension type oral administration solution.
6. slow releasing preparation according to claim 1, it is characterised in that: described slow-release material is the slow-release material comprising polyacrylic resin class or ethyl cellulose type.
7. slow releasing preparation according to claim 1, it is characterized in that: in suspension type oral administration solution, its solvent adopted is deionized water, and the suspending agent of employing is be combined with the arabic gum of one or more in hypromellose class or carboxymethyl cellulose class or sodium alginate or carbomer series or xanthan gum；The flavoring agent adopted is sorbitol or fructose class；The ion chelating agent adopted is ethylenediaminetetraacetic acid, disodiumedetate, a kind of or arbitrarily several mixture in disodiumedetate, diethyl pentetic acid disodium；The acidity regulator adopted is hydrochloric acid or citric acid buffer salt or phosphoric acid buffer salt；The preservative adopted is parabens.
8. the method for the slow releasing preparation preparing the arbitrary described hydrochloric trazodone oral administration solution of the claims 1-7, it is characterised in that include step: A: adopt trazodone hydrochloride and resin ion to carry out ion-exchange step, obtain trazodone resinous polymer；B: adopt the slow-release material comprising polyacrylic resin or ethyl cellulose that trazodone resinous polymer is carried out coating, obtain trazodone resin dressing microcapsule；C: adopt deionized water and trazodone resin dressing microcapsule, prepares suspension type oral administration solution.
9. method according to claim 8, it is characterised in that: in step B, trazodone resin dressing microcapsule is to adopt heat drying or heating evacuation or lyophilization step to make.
10. method according to claim 8, it is characterised in that: also include step D: using brown polyester bottles or vial additional shading carton that suspension type oral administration solution is packed, the medicine liquid volume of each minimum package is 5～500ml.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN106975080A (en) * | 2017-03-31 | 2017-07-25 | 安徽安生生物化工科技有限责任公司 | A kind of polyacrylic resin IV aqueous dispersions as coating material application |
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Application publication date: 20160629 |