CN112494456B - Ethyl cellulose hollow microcapsule - Google Patents
Ethyl cellulose hollow microcapsule Download PDFInfo
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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
- A61K9/48—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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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
- A61J3/00—Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms
- A61J3/07—Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms into the form of capsules or similar small containers for oral use
- A61J3/071—Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms into the form of capsules or similar small containers for oral use into the form of telescopically engaged two-piece capsules
- A61J3/077—Manufacturing capsule shells
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- 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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
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- 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
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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
- A61K9/48—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
- A61K9/5089—Processes
Abstract
The invention discloses a preparation method of an ethyl cellulose hollow microcapsule, which comprises the following steps: (1) mixing a surfactant, a viscosity additive and deionized water according to a mass ratio of 1:5:100, uniformly stirring at the temperature of 60 ℃, and cooling to obtain the aqueous phase solution; (2) mixing 2-9% polyglycerol polyricinoleate, 5-10% ethyl cellulose and ethyl acetate according to a mass ratio of 4:5:100, and uniformly stirring at normal temperature to obtain an oil phase solution; according to the invention, the outlet of the micro-channel is in a conical structure, so that the aqueous phase solution fluid shears the oil phase solution fluid to form a monodisperse oil-in-water emulsion, and the oil phase in the oil-in-water emulsion has a volatilization characteristic to prepare the EC micro-capsule structure with a hollow structure; compared with the prior art, the method has the advantages of simple and convenient operation, controllable particle size, low raw material consumption and the like.
Description
Technical Field
The invention belongs to the field of polymer particles, and particularly relates to an ethyl cellulose hollow microcapsule and application thereof, and a method and a device for manufacturing the ethyl cellulose hollow microcapsule.
Background
The hollow polymer particles have a large cavity and are often used to coat drugs, enzymes, proteins, etc. Ethyl Cellulose (EC) is a hydrophobic material with good biocompatibility, and has wide application in the fields of biology and medicine. In recent years, many documents report the advantages of hollow EC microcapsules in sustained-release pharmaceutical formulations. The preparation methods of the hollow EC microcapsules include a spray drying method, a membrane emulsification method, a multiple emulsion method and the like, but the preparation processes of the methods are complex to operate and difficult to control the particle size, so that the application of the hollow EC microcapsules in the field of biomedicine is limited to a certain extent.
Disclosure of Invention
The invention aims to provide a preparation method of an ethyl cellulose hollow microcapsule, which can be used for preparing an ethyl cellulose microcapsule with a hollow structure and can be used as a drug coating film.
In order to achieve the purpose, the invention is realized by adopting the following technical scheme:
a preparation method of an ethyl cellulose hollow microcapsule comprises the following steps:
(1) preparation of an aqueous solution
Mixing a surfactant, a viscosity additive and deionized water according to a mass ratio of 1:5:100, uniformly stirring at the temperature of 60 ℃, and cooling to obtain the aqueous phase solution;
(2) preparation of oil phase solution
Mixing a polyglycerol polyricinoleate solution with the concentration of 2-9%, an ethyl cellulose solution with the concentration of 5-10% and ethyl acetate according to the mass ratio of 4:5:100, and uniformly stirring at normal temperature to obtain an oil phase solution;
(3) preparation of hollow EC microcapsules
Conveying the oil-phase solution and the water-phase solution into a micro-channel according to a fluid velocity ratio of 1:5, wherein an outlet of the micro-channel is conical, the water-phase solution fluid shears the oil-phase solution fluid to form a monodisperse oil-in-water emulsion, and the oil-in-water emulsion enables the oil-water two phases to be subjected to mass transfer after standing for 1h and volatilizes the oil-phase solution to obtain a hollow EC micro-capsule;
(4) washing machine
And washing the hollow EC microcapsule by deionized water, and drying to obtain the ethyl cellulose hollow microcapsule.
According to the invention, the outlet of the micro-channel is of a conical structure, so that the water phase solution fluid shears the oil phase solution fluid to form a monodisperse oil-in-water emulsion, the oil phase in the oil-in-water emulsion has the volatilization characteristic, the oil-water two phases are fully subjected to mass transfer in the standing process, and the oil phase solution is volatilized to prepare the EC micro-capsule structure with a hollow structure; compared with the prior art, the method has the advantages of simple and convenient operation, controllable particle size, low raw material consumption and the like.
Further, the surfactant in the step (1) is a Pluronic F127 solution with the concentration of 0.2-2%, and the viscosity additive is a polyvinyl alcohol solution with the concentration of 5-15%.
The Pluronic F127 solution is used as a surfactant of the water phase solution, and the Pluronic F127 solution can be used as an oral medicine, so that the EC microcapsule can be used as a medicine coating film in the following process.
The medical polyvinyl alcohol solution is used as a viscosity additive, is a safe high-molecular organic matter, has no toxicity or side effect on a human body, and has good biocompatibility.
Preferably, the aqueous phase solution comprises 1% Pluronic F127, 5% polyvinyl alcohol and deionized water in a mass ratio of 1:5: 100.
The above components giving the preferential mass ratio of the aqueous phase solution for making the hollow EC microcapsules may also be replaced by polyethylene glycol in the polyvinyl alcohol solution of the aqueous phase solution, or by mixing both polyvinyl alcohol and polyethylene glycol.
Preferably, the oil phase solution comprises 6% polyglycerol polyricinoleate solution, 5% ethylcellulose solution and ethyl acetate in a mass ratio of 4:5: 100.
The above-mentioned components giving the preferential mass ratio of the oil phase solution for producing the hollow EC microcapsules, while the ethyl acetate is used as a volatile agent, may be replaced by the solvent having good volatility such as toluene, xylene, chloroform, and the like.
Preferably, the fluid velocity of the oil phase solution is 5 μ L/min and the fluid velocity of the aqueous phase solution is 25 μ L/min.
The invention also provides the ethyl cellulose hollow microcapsule prepared by the preparation method of the ethyl cellulose hollow microcapsule. The microcapsule has a hollow structure, can be used for containing a medicament in the hollow cavity and can be used as a medicament coating film, and can be applied to the field of biological medicines.
The invention also provides a device for manufacturing the ethyl cellulose hollow microcapsule, which comprises a first injection pump, a second injection pump, a microchannel and a collecting pipe, wherein the microchannel comprises a pipe body, two inlets and an outlet which are arranged on the pipe body, the first injection pump and the second injection pump are respectively communicated with the two inlets, the outlet of the microchannel is in a conical shape, the diameter of the outlet is gradually reduced along the flowing direction of the solution, and the outlet of the microchannel is communicated with the collecting pipe.
The micro-channel is connected with two injection pumps, the flow rates of oil-phase solution and water-phase solution are controlled by controlling the injection pumps, then the water-phase solution at the tapered outlet of the micro-channel has high speed, and interfacial tension and viscous force act to shear the oil-phase solution and form monodisperse oil-in-water emulsion, and the oil-in-water emulsion is collected into a container through a collecting pipe.
Furthermore, the first injection pump and the second injection pump adopt micro-sampling electronic injection pumps with controllable flow rate.
The micro-sampling electronic injection pump with controllable flow rate realizes the automatic control of the flow rate of the water phase and the oil phase, can realize the industrialized mass production, and has good quality of the produced microcapsules.
Furthermore, the diameter of the pipe body of the micro-channel is 550 micrometers, the length of a conical outlet at one end of the micro-channel is 4.5cm, and the minimum diameter of the micro-channel is 50-80 micrometers; the diameter of the collecting pipe is 500 mu m, the collecting pipe is connected with a PE hose, and one end of the PE hose is immersed in deionized water in the collecting container.
The invention provides the optimal micro-channel structure parameters, so that the EC micro-capsules produced by the invention have excellent structures and are suitable for batch production of the EC micro-capsules.
Drawings
FIG. 1 is a flow chart of the manufacturing method of the present invention.
FIG. 2 is a schematic diagram of the microcapsule formation process of the present invention.
FIG. 3 is a schematic structural diagram of a manufacturing apparatus according to the present invention.
Fig. 4 is a scanning electron microscope image of the whole EC microcapsules with different PGPR contents.
FIG. 5 is a scanning electron micrograph of sections of EC microcapsules of different PGPR content.
FIG. 6 is a scanning electron micrograph of microcapsules of different EC content
Figure 7 is an in vitro release profile of microcapsules at three different drug loadings in a pH 6.8 release medium.
Figure 8 is an in vitro release profile of microcapsules at three different drug loadings in a pH 7.4 release medium.
The labels in the figure are: 10. a microchannel; 11. a conical outlet; 21. a first syringe pump; 22. a second syringe pump; 30. a collection pipe; 40. a collection container; 50. a hose; 60. and (4) square tubes.
Detailed Description
Example 1
The hollow ethyl cellulose microcapsule provided by the embodiment can be used for coating medicines, enzymes, proteins and the like. In this example, the hollow microcapsule is prepared by a method with simple operation and controllable particle size.
As shown in fig. 1, the preparation method comprises the following steps:
(1) preparation of an aqueous solution
Taking 0.5g of Pluronic F127 solution with the concentration of 1%, 2.5g of polyvinyl alcohol solution with the concentration of 5% and 50ml of deionized water, putting the mixture into a beaker, mixing, putting the beaker into a water bath kettle with the temperature of 65 ℃, uniformly stirring, and cooling to obtain the aqueous phase solution.
(2) Preparation of oil phase solution
0.4g of polyglycerol polyricinoleate solution with the concentration of 5%, 0.5g of ethyl cellulose solution with the concentration of 6% and 10ml of ethyl acetate are put into a beaker to be mixed, and the mixture is stirred uniformly at normal temperature to obtain oil phase solution.
(3) Preparation of hollow EC microcapsules
The hollow EC microcapsule is prepared by using a single-stage microfluidic device, as shown in fig. 3, the single-stage microfluidic device includes a first syringe pump 21, a second syringe pump 22, a microchannel 10 and a collection container 40, the microchannel 10 includes a tube body with a diameter of 550 μm, and two inlets and one outlet 11 disposed on the tube body, the two inlets are respectively communicated with the first syringe pump 21 and the second syringe pump 22, the first syringe pump 21 and the second syringe pump 22 both adopt a microinjection electronic syringe pump with a controllable flow rate, and the aqueous phase solution prepared in step (1) and the oil phase solution prepared in step (2) are respectively loaded into the first syringe pump 21 and the second syringe pump 22. The outlet 11 of the micro-channel 10 is conical, as shown in fig. 3, the diameter of the outlet 11 is gradually reduced along the solution flowing direction, the length of the outlet is 4.3mm, the minimum diameter of the outlet 11 is 50-80 μm, the outlet 11 of the micro-channel 10 is communicated with a collecting pipe 30 with the diameter of 500 μm and the length of 6cm, the collecting pipe 30 is communicated with a collecting container 40 filled with deionized water through a hose 50, and a square pipe 60 is sleeved on the outer wall of the contact part of the micro-channel 10 and the collecting pipe 30 for fixing the micro-channel 10 and the collecting pipe 30.
Controlling the flow rate of the first injection pump 21 filled with the water phase solution to be 25 muL/min and the flow rate of the second injection pump 22 filled with the oil phase solution to be 5 muL/min, when the water phase solution and the oil phase solution are at the conical outlet 11, the oil phase solution can be sheared due to the faster flow rate of the water phase solution and the action of interfacial tension and viscous force to form a monodisperse oil-in-water (O/W) emulsion, standing for 1h, and the oil-in-water emulsion enables the mass transfer of the oil phase and the water phase to be sufficient and the oil phase solution to volatilize to obtain the hollow EC microcapsule.
(4) Washing machine
Washing the hollow EC microcapsule with deionized water, and drying to obtain an ethyl cellulose hollow microcapsule, as shown in figure 2, a hollow EC microcapsule forming process; the O/W emulsion prepared by the single-stage microfluidic device is used as a template, and because ethyl acetate has stronger volatility and certain water solubility, water molecules and the water molecules perform mass transfer with each other at an oil-water interface, the water molecules enter an oil phase through the oil-water interface and are aggregated to form large water drops, and after the EC molecules are solidified, the water drops form a hollow cavity inside the EC microcapsule.
Study of the Effect of the PolyGlycerol ricinoleate (PGPR) content on microcapsules
The microcapsules were prepared according to the apparatus and method provided in example 1 using PGPR concentrations of 0%, 2%, 4% and 9%, respectively, and observed under a Scanning Electron Microscope (SEM).
As shown in fig. 4, the scanning electron microscope images of the whole EC microcapsules with different PGPR contents. PGPR contents were 0% (w/v) (a), 2% (w/v) (b), 4% (w/v) (c), and 9% (w/v) (d), respectively, on a scale of 50 μm. As can be seen from the figure: the microcapsule without PGPR content (0%) has a porous structure on the surface; the surface of the microcapsule with the PGPR content of 2 percent has small concave pits; the microcapsule with the PGPR content of 4% concentration has large-size concave pits on the surface; the microcapsules with a concentration of 9% PGPR contained had a large-sized depression on the surface side, occupying almost half of the space of the microcapsules. Under the condition of constant addition amount, the content of PGPR is increased along with the increase of the concentration of PGPR; this indicates that: with the increase of the content of PGPR in the oil phase, the size of the depressions on the surface of the microcapsules will be larger and larger until half of the space of the microcapsules is occupied. After the EC is solidified to form a microcapsule film, water drops concentrated on an oil-water interface can be broken, so that pits with different sizes are formed on the surface of the capsule wall.
As shown in fig. 5, sem images of sections of EC microcapsules with different PGPR content. PGPR content was 0% (w/v) (a), 2% (w/v) (b), 4% (w/v) (c), 6% (w/v) (d), respectively, and the scale was 50 μm, as can be seen from the figure: the inside of the microcapsules without PGPR content (0%) exhibited a porous structure but no cavity portion; the inside of the microcapsule with the concentration of 2 percent of PGPR content is loose and porous and has a cavity; the microcapsule with the concentration of 4% of PGPR content has a compact internal structure and a larger cavity; microcapsules with a concentration of 6% PGPR content have a dense internal structure and large cavities. This indicates that: with the increase of the PGPR content of the oil phase, the internal cavity of the microcapsule is larger and larger, water molecules in the water phase can more easily pass through an oil-water interface due to the increase of the PGPR content of the surfactant, a large number of water molecules pass through the phase interface to be diffused into the emulsion to be gathered to form larger water drops, and the water drops form the cavity of the microcapsule after the EC is solidified into a capsule layer. Therefore, the more PGPR content in the oil phase, the larger the microcapsule internal cavity, and the microcapsule wall layer structure becomes dense from porous.
Effect of ethylcellulose EC content on microcapsules
The microcapsules were prepared according to the apparatus and method provided in example 1 using ethylcellulose EC at concentrations of 5%, 6%, 7% and 8%, respectively, and the microcapsules were observed under a Scanning Electron Microscope (SEM).
As shown in fig. 6, scanning electron micrographs of microcapsules of different EC contents. Scanning electron micrographs of microcapsules (a) with a concentration of 5% EC content and their sections (b); scanning electron micrographs of microcapsules (c) with an EC content of concentration 6% and their sections (d); scanning electron micrographs of microcapsules (e) with a concentration of 7% EC content and their sections (f); scanning electron micrographs, on a 25 μm scale, of microcapsules (g) with an EC content of 8% concentration and of their section (h).
As can be seen from the figure: when the EC concentration is 5%, the size of the inner cavity of the microcapsule is 84 μm; when the EC concentration is 6%, the size of the inner cavity of the microcapsule is 70 μm; when the EC concentration is 7%, the size of the inner cavity of the microcapsule is 55 μm; at an EC concentration of 8%, the internal cavity size of the microcapsules was 50 μm. This indicates that: the size of an internal cavity is gradually reduced along with the increase of the EC content in the oil phase, when the interface of the O/W emulsion is subjected to mass transfer, the ethyl acetate of the oil phase is diffused outwards, water molecules of the water phase are diffused inwards, the ethyl acetate of the oil phase is gradually diffused towards the water phase and volatilizes, the higher the EC content in the oil phase is, the higher the separation speed of the EC is, the separated EC can form a capsule membrane which has resistance to the mass transfer of the water molecules inwards, and the water molecules capable of being diffused into the oil phase are fewer, so that the size of water drops which are combined in the oil phase is smaller, and the size of the cavity formed in the microcapsule after the EC is solidified is smaller.
Influence of flow Rate ratio (external phase: internal phase) on microcapsule size and monodispersity EC microcapsules were prepared at different flow Rate ratios.
EC microcapsules were prepared according to the method of example 1 with flow rate ratios (outer phase: inner phase) of 3, 5, and 10, respectively, and the microcapsules had uniform and normal particle diameters, and the variation coefficients (CV values) of the particle diameters of the microcapsules with flow rate ratios of 3, 5, and 10 were calculated to be 2.8%, 2.2%, and 3.1%, respectively, and less than 5%, indicating that the monodispersity of the microcapsules prepared at different flow rate ratios was good, and the monodispersity of the microcapsules with flow rate ratio of 5 was the best. Meanwhile, when the flow rate ratio is 3, the average grain diameter of the microcapsule is 158 μm; when the flow rate ratio is 5, the average particle diameter of the microcapsule is 141 μm; when the flow rate ratio was 10, the average particle size of the microcapsules was 107 μm. This indicates that: the average particle size of the microcapsules decreases as the flow rate ratio increases. This is because the increase in the flow rate ratio strengthens the shearing action between the oil and water phases, and the size of the emulsion cut by the cone is reduced, thereby reducing the particle size of the cured microcapsule.
Microcapsule controlled Release Properties Studies
The microcapsules were loaded with different amounts of the drug (6.14%, 10.44% and 13.7%) and tested for release in a weakly acidic pH of 6.8 and a weakly alkaline pH of 7.4, respectively.
As shown in fig. 7, in a release medium with a pH of 6.8, the microcapsules with drug loading of 6.14% and 10.44% exhibit a rapid-first-slow release characteristic, which is consistent with the characteristics of a general sustained-release preparation, and after the release time reaches 8 hours, the release curve of the drug is gentle, the drug is no longer released, and the cumulative release rates of the drug reach 99.06% and 99.13%, respectively; the microcapsule with 13.7 percent of drug loading rate shows the release characteristic of constant speed, accords with the characteristic of zero-order sustained release preparation, and when the release time reaches 4 hours, the drug is completely released, and the cumulative release rate of the drug reaches 100 percent. In the process of releasing the medicine-carrying microcapsules, the accumulative release rate of the low-medicine-carrying-capacity microcapsules is lower than that of the high-medicine-carrying-capacity microcapsules, and because the medicine in the high-medicine-carrying-capacity microcapsules occupies more space of a microcapsule layer, when a release medium dissolves the medicine, more pore channels are formed, and the medicine release rate is higher.
As shown in fig. 8, in a release medium with pH 7.4, the microcapsules with three different drug loading rates all show a non-constant-rate release characteristic of rapid-first and slow-second, which is consistent with the characteristics of a general sustained-release preparation. The drug release profile gradually flattens as the in vitro release time increases. When the release time reaches 6h, the cumulative release rate of the 6.14 percent drug-loaded microcapsule drug reaches 86.13 percent; when the release time reaches 12h, the cumulative release rate of the microcapsule medicament with the drug loading of 10.44 percent reaches 99.79 percent; when the release time reaches 10h, the cumulative release rate of the microcapsule medicament with 13.7 percent of medicament loading reaches 100 percent. In the process of releasing the medicine-carrying microcapsules, the accumulative release rate of the low-medicine-carrying-capacity microcapsules is lower than that of the high-medicine-carrying-capacity microcapsules, because the medicine in the high-medicine-carrying-capacity microcapsules occupies more space of a microcapsule layer, when a release medium dissolves the medicine, more pore channels are formed, and the medicine release rate is higher.
In this embodiment, a single-stage microfluidic device is used to prepare a highly monodisperse O/W emulsion, which is used as a template to cause EC phase separation by mass transfer between water molecules and a volatile water-soluble organic solvent, ethyl acetate, to form an EC microcapsule with a hollow structure. The microcapsule prepared under the conditions of different flow rate ratios has uniform grain diameter and good monodispersity. Meanwhile, as the flow rate ratio increases, the average particle diameter of the microcapsules decreases. In the process of oil-water interface mass transfer, with the increase of the content of PGPR in the oil phase, mass transfer of water molecules to the oil phase is easier, and a large number of water molecules are converged at the phase interface and diffused to the oil phase, and are converged at the interface to form a plurality of water drops. The formation of the internal cavity of the microcapsule is closely related to the content of PGPR, when the content of PGPR in the oil phase is 0, the internal part of the microcapsule has no cavity structure, and the cavity structure appears in the internal part of the microcapsule and the cavity size is increased along with the increase of the content of PGPR in the oil phase. As the EC content increases, the microcapsule internal cavity size decreases.
The in vitro release properties of three different drug loaded microcapsules in two release media pH 6.8 and pH 7.4 were studied. The results show that: the drug loading is an important factor influencing drug release, the lower the drug loading, the smaller the cumulative release rate of the microcapsule, and in a release medium with the pH value of 6.8, the microcapsule with the drug loading of 6.14% has the best sustained release effect, when the drug release time reaches 8h, the cumulative release rate is 99%, and the drug is basically released completely; in a release medium with pH 7.4, the microcapsule with 6.14 percent of drug loading has better sustained release effect, but the drug release time is only 6 hours and the drug release is incomplete, and the drug release time of the microcapsule with 10.44 percent of drug loading can reach 12 hours. In vitro release of 6.14% and 10.44% drug loaded microcapsules in a release medium at pH 6.8 follows Higuchi's equation, with the release rate being governed by diffusion laws. The in vitro release of the 13.7% drug-loaded microcapsules conforms to the zero-order release equation, the release rate is independent of time and may be related to the erosion disintegration of the microcapsules; in a release medium with pH 7.4, the in vitro release of the microcapsules with three different drug loading rates conforms to a first-order release equation, and the release rate is in direct proportion to the time.
The above description is only a preferred embodiment of the present invention, but the scope of the present invention is not limited thereto, and any modification and replacement based on the technical solution and inventive concept provided by the present invention should be covered within the scope of the present invention.
Claims (9)
1. A preparation method of an ethyl cellulose hollow microcapsule is characterized by comprising the following steps:
(1) preparation of an aqueous solution
Mixing 0.2-2% Pluronic F127 solution, 5-15% polyvinyl alcohol solution and deionized water according to the mass ratio of 1:5:100, uniformly stirring at the temperature of 60 ℃, and cooling to obtain the water phase solution;
(2) preparation of oil phase solution
Mixing a polyglycerol polyricinoleate solution with the concentration of 2-9%, an ethyl cellulose solution with the concentration of 5-10% and ethyl acetate according to the mass ratio of 4:5:100, and uniformly stirring at normal temperature to obtain an oil phase solution;
(3) preparation of hollow EC microcapsules
Conveying the oil-phase solution and the water-phase solution into a micro-channel according to a fluid velocity ratio of 1: 3-10, wherein an outlet of the micro-channel is conical, the diameter of the outlet is gradually reduced along the flow direction of the solution, the oil-phase solution fluid shears the oil-phase solution fluid to form a monodisperse oil-in-water emulsion, and the oil-in-water emulsion enables the oil-phase solution and the water-phase solution to be fully mass-transferred and volatilize after standing for 1h to obtain a hollow EC micro-capsule with a concave pit on the outer surface;
(4) washing machine
And washing the hollow EC microcapsule by deionized water, and drying to obtain the ethyl cellulose hollow microcapsule.
2. The method for preparing the ethylcellulose hollow microcapsule according to claim 1, characterized in that: the aqueous phase solution comprises 1% Pluronic F127 solution, 5% polyvinyl alcohol solution and deionized water in a mass ratio of 1:5: 100.
3. The method for preparing an ethylcellulose hollow microcapsule according to claim 1, characterized in that: the oil phase solution comprises 6% polyglycerol polyricinoleate solution, 5% ethyl cellulose solution and ethyl acetate according to the mass ratio of 4:5: 100.
4. The method for preparing an ethylcellulose hollow microcapsule according to claim 1, characterized in that: the fluid velocity of the oil phase solution is 5 muL/min, and the fluid velocity of the water phase solution is 25 muL/min.
5. An ethylcellulose hollow microcapsule prepared by the method for preparing the ethylcellulose hollow microcapsule according to any one of claims 1 to 4.
6. Use of the ethylcellulose hollow microcapsules according to claim 5 in biomedicine for preparing drug-coated membranes.
7. An ethylcellulose hollow microcapsule according to claim 5, characterized in that: the device for manufacturing the ethyl cellulose hollow microcapsules comprises a first injection pump, a second injection pump, a microchannel and a collecting pipe, wherein the microchannel comprises a pipe body, two inlets and an outlet, the two inlets and the outlet are arranged on the pipe body, the first injection pump and the second injection pump are respectively communicated with the two inlets, the outlet of the microchannel is in a conical shape, the diameter of the outlet is gradually reduced along the flowing direction of a solution, and the outlet of the microchannel is communicated with the collecting pipe.
8. An ethylcellulose hollow microcapsule according to claim 7, characterized in that: the first injection pump and the second injection pump adopt micro-sampling electronic injection pumps with controllable flow rate.
9. An ethylcellulose hollow microcapsule according to claim 7, characterized in that: the diameter of the pipe body of the micro-channel is 550 micrometers, the length of a conical outlet at one end of the micro-channel is 4.5cm, and the minimum diameter of the micro-channel is 50-80 micrometers; the diameter of the collecting pipe is 500 mu m, the collecting pipe is connected with a PE hose, and one end of the PE hose is immersed in deionized water in the collecting container.
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