CN105943504A - Method for preparing pharmaceutic adjuvant Eudragit RS100 particle - Google Patents

Method for preparing pharmaceutic adjuvant Eudragit RS100 particle Download PDF

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Publication number
CN105943504A
CN105943504A CN201610262443.7A CN201610262443A CN105943504A CN 105943504 A CN105943504 A CN 105943504A CN 201610262443 A CN201610262443 A CN 201610262443A CN 105943504 A CN105943504 A CN 105943504A
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CN
China
Prior art keywords
eudragit
solution
pharmaceutic adjuvant
microgranule
polymer
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Pending
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CN201610262443.7A
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Chinese (zh)
Inventor
王辉
甄崇礼
卢建红
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Changzhou Institute for Advanced Materials Beijing University of Chemical Technology
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Changzhou Institute for Advanced Materials Beijing University of Chemical Technology
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Priority to CN201610262443.7A priority Critical patent/CN105943504A/en
Publication of CN105943504A publication Critical patent/CN105943504A/en
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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
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1629—Organic macromolecular compounds
    • A61K9/1635—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
    • 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
    • A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
    • 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

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Epidemiology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Engineering & Computer Science (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Inorganic Chemistry (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The invention discloses a method for preparing a pharmaceutic adjuvant Eudragit RS100 particle. The method processes the Eudragit RS100 polymer solution of polyvinylpyrrolidone (A) added a dispersing agent (B) by solution-enhanced dispersion by supercritical technology to obtain the polymer particle, and is used for preparing slow/controlled-release particle pharmaceutic preparation. The medicine can be performed microparticulation (microencapsulation) by means of the method condition of preparing particle by the pharmaceutic adjuvant controlled-release packing material Eudragit RS100, the side effects of pharmaceutical medicine and the frequency of taking medication are reduced, and the use ratio of the medication in vivo is improved.

Description

A kind of method preparing pharmaceutic adjuvant Eudragit RS100 microgranule
Technical field
The present invention relates to a kind of method preparing slow/controlled release coating material polymer particles in field of medicaments.
Background technology
The microencapsulation of medicine is to utilize naturally occurring or synthetic pharmaceutical polymers for capsule material, and medicine dispersion or encapsulating are formed microgranule in the material.The slow/controlled release of drug microparticles compared with other slow-release controlled-release preparation techniques (such as matrix type controlled release tablet, coated slow release technology, osmotic pump preparation etc.), due to the particle diameter of drug microparticles little, it is prone to adhere to, can increase medicine and the contact area of site of action and time of contact, bioavailability is high；Interaction and the compatible change of compound medicine can be reduced simultaneously；Can not only control the rate of release of medicine, moreover it is possible to by the modification to drug microparticles surface, becoming can timing, location drug delivery system.The application prospect huge due to it and the change to convenient administration mode, this research field is in recent years by the extensive concern of Chinese scholars, and the application in terms of medicament slow release and controlled release achieves huge progress.In various microencapsulation methods, preparing particle diameter drug microparticles that is little and that be evenly distributed is a new challenge.
Summary of the invention
It is an object of the invention to as preparing that particle diameter is little and the slow/controlled release drug microparticles of narrow particle size distribution provides method and condition.
The method condition preparing pharmaceutically acceptable polymer Eudragit RS100 microsphere that the present invention provides, is to be dissolved in a certain amount of organic solvent by pharmaceutically acceptable polymer Eudragit RS100, Solution-enhanced dispersion by supercritical makes spherical particle.Described organic solvent is DMF (DMF), separately need to add quantitative polyethylene of dispersing agent ketopyrrolidine (PVP).
The consumption of described pharmaceutically acceptable polymer Eudragit RS100 is 80mg, and is dissolved in the DMF of 10mL, is configured to the solution that concentration is 8mg/mL, adds different quality dispersant PVP, and its consumption is 20～120mg, obtains settled solution.
In described Solution-enhanced dispersion by supercritical, the pressure of carbon dioxide is 8.0MPa, and temperature is 35.0 DEG C, and charging rate is 0.5mL/min, and carbon dioxide outlet flow velocity is 100L/h.
Can add medicine in the solution of described pharmaceutically acceptable polymer Eudragit RS100, adopting said method prepares that particle diameter is little and the slow/controlled release pharmaceutical preparation microgranule of narrow particle size distribution.
The present invention utilizes Solution-enhanced dispersion by supercritical to prepare Eudragit RS100 pharmaceutically acceptable polymer microgranule, explores the condition preparing the little Eudragit RS100 polymer spherical microgranule of particle diameter.It is thus possible under this preparation condition, add the medicine that can dissolve in the solution of this polymer, prepare, by Solution-enhanced dispersion by supercritical, the pharmaceutical preparation microgranule that particle diameter is less.Allow medicament to slow release or constant release, contacting and action time of pharmaceutical preparation microgranule and active area can be increased substantially, significantly improve its bioavailability and alleviate its side reaction in human body.The method has the advantages such as technique is simple, easily controllable.The method utilizing the present invention can prepare the pharmaceutical preparation microgranule with certain particle diameter, adds the approach of drug delivery, the most beneficially human body and obtains the most effectively therapeutic plasma concentrations, is the utilization rate optimization of medicine, has broad application prospects.
Accompanying drawing explanation
Fig. 1 is that Solution-enhanced dispersion by supercritical (SEDS) prepares Eudragit RS100 polymer particles flow chart.
Fig. 2 is the mass ratio of Eudragit RS100 when being 50% (w/w), prepares the electromicroscopic photograph of Eudragit RS100 polymer particles.
Detailed description of the invention
The preparation of Eudragit RS100 spherical particle.
This example is to prepare Eudragit RS100 polymer spherical microgranule by Solution-enhanced dispersion by supercritical.Wherein preparing particle device is Solution-enhanced dispersion by supercritical (SEDS) device, as shown in Figure 1.
(1) the Eudragit RS100 first weighing 80mg is dissolved in the DMF solvent of 10ml, adds the PVP of certain mass, fully dissolves.
(2) controlled the temperature in water bath by heater, be accurate to ± 0.1 DEG C.The CO provided by steel cylinder2In plunger displacement pump is injected into whole device, then the pressure by ISCO pump control system, after being raised to the pressure set, it is accurate to ± 0.1MPa, stabilising arrangement pressure and temperature 30min.
(3) then, open and regulate CO2Outlet valve, by the pressure of ISCO pump control system constant in the case of, start HPLC constant flow pump in autoclave, inject Eudragit RS100 polymer solution with the flow velocity of 0.5mL/min.Wherein solution walks the inner tube (diameter 1.5mm) of coaxial nozzle of autoclave, and the CO injected2Walk outer tube (diameter 3.1mm).
(4) after solution adds, close HPLC pump and respective valves, continue to inject CO2, rinsing the organic solvent of residual, washing time is 50min.CO2The organic solvent that gas is taken out of is collected, and CO2The flow of gas is measured by gas flowmeter.
(5) stop ISCO pump, close respective valves, and to system release, obtain Eudragit RS100 polymer spherical microgranule.
(6) product in step (5) is scanned electronic microscope photos by scanning electron microscope (SEM), analyzes size and the pattern of microgranule.Wherein gained Eudragit RS100 polymer particles particle diameter is at about 500nm, and size is homogeneous, is evenly distributed.
The present invention successfully prepares the Eudragit RS100 polymer particles that particle diameter is less, and it has the feature such as narrower particle size distribution and preferable pattern.It is essential that thus prepare relatively small particle pharmaceutical preparation microgranule, increase the approach of drug delivery, increase substantially adhesion and the time of contact of medicine and site of action, thus improve the bioavailability of medicine and alleviate side effects of pharmaceutical drugs.The present invention successfully prepares pharmaceutically acceptable polymer Eudragit RS100 spherical particle, explores the condition obtaining microgranule, provides method and reference for preparing slow/controlled release pharmaceutical preparation microgranule.

Claims (6)

1. the method preparing pharmaceutic adjuvant Eudragit RS100 microgranule, pharmaceutic adjuvant Eudragit RS100 Polymer solution, by (A) model be the polyacrylic resin 80mg of Eudragit RS100, (B) gather Vinylpyrrolidone measures 20～120mg, (C) DMF composition 10ml, uses high density CO2 Gas prepares polymer particles by Solution-enhanced dispersion by supercritical.
The method preparing pharmaceutic adjuvant Eudragit RS100 microgranule the most according to claim 1, its feature It is, described polymer solution that, based on the weight of compositions, the weight ratio shared by component A is 40%～80%, Component C is organic solvent, and the concentration of configuration solution is 8mg/mL.
The method preparing pharmaceutic adjuvant Eudragit RS100 microgranule the most according to claim 1, its feature It is that the described conditional parameter strengthened in solution dispersive process, wherein pressure is 8.0MPa, and temperature is 35.0 DEG C, its charging rate is 0.5mL/min, and carbon dioxide outlet flow velocity is 100L/h.
The method preparing pharmaceutic adjuvant Eudragit RS100 microgranule the most according to claim 1, its feature It is, described high density gas CO2Eudragit is prepared by Solution-enhanced dispersion by supercritical The method of RS100 polymer particles, comprises the steps:
(1) configuration of Eudragit RS100 polymer solution: weigh a certain amount of Eudragit RS100 polymerization Thing, joins in a certain amount of DMF solvent, dissolves fully, adds polyethylene of dispersing agent Ketopyrrolidine, stirring is to clear solution；
(2) by ISCO pump and water bath device, enhancing solution dispersal device is pressurized to 8.0MPa and 35.0 DEG C, Again by HPLC pump solution with the speed injection of polymer of 0.5mL/min in autoclave, inject solution extremely Full dose；
(3) after polymer particles fully separates out, by CO2The polymer particles product of gained is dried.
5. the method preparing pharmaceutic adjuvant Eudragit RS100 microgranule described in claim 4, its feature exists In, described step (2) is:
(1) CO is first used2Gas washes out the air in device, then by water bath device, device is warmed up to 35 DEG C, Then, then device is pressurized to 8.0MPa, while the pressure and temperature of stabilisation systems, keeps 30min；
(2), while being injected solution by coaxial nozzle in autoclave, CO is opened2Outlet valve, washes out wherein Organic solvent, the outer tube diameter of coaxial nozzle is 3.1mm, and the internal diameter of inner tube is 1.5mm.
6. the method preparing pharmaceutic adjuvant Eudragit RS100 microgranule described in claim 4, its feature exists In, described step (3) is: after injection solution completes, continue to be passed through CO2Gas 50min, makes gained The polymer particles arrived is the driest.
CN201610262443.7A 2016-04-25 2016-04-25 Method for preparing pharmaceutic adjuvant Eudragit RS100 particle Pending CN105943504A (en)

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Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103932989A (en) * 2014-02-24 2014-07-23 北京化工大学常州先进材料研究院 Method used for preparing pharmaceutic adjuvant Eudragit RL100 polymer particulates

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103932989A (en) * 2014-02-24 2014-07-23 北京化工大学常州先进材料研究院 Method used for preparing pharmaceutic adjuvant Eudragit RL100 polymer particulates

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
JUPPO ET AL.: "Evaluation of solid dispersion particles prepared with SEDS", 《INTERNATIONAL JOURNAL OF PHARMACEUTICS》 *
刘亮等: "超临界流体强化溶液分散法制备Eudragit S100 纳米颗粒", 《现代生物医学进展》 *
方亮: "《药用高分子材料学》", 31 August 2015 *
窦若岸: "超临界二氧化碳技术制备聚合物微粒及载药微粒", 《中国优秀硕士学位论文全文数据库 工程科技Ⅰ辑》 *

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