CN116898820A - Method for preparing cyclosporine solid dispersion based on electrostatic spinning technology - Google Patents

Method for preparing cyclosporine solid dispersion based on electrostatic spinning technology Download PDF

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Publication number
CN116898820A
CN116898820A CN202310856811.0A CN202310856811A CN116898820A CN 116898820 A CN116898820 A CN 116898820A CN 202310856811 A CN202310856811 A CN 202310856811A CN 116898820 A CN116898820 A CN 116898820A
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China
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solid dispersion
preparing
cyclosporine
electrostatic spinning
dispersion based
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CN202310856811.0A
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Chinese (zh)
Inventor
刘洪斌
黄天强
何达
许崇礼
马郑
黄治民
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Zhejiang Arthur Pharmaceutical Co ltd
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Zhejiang Arthur Pharmaceutical Co ltd
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Priority to CN202310856811.0A priority Critical patent/CN116898820A/en
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    • D—TEXTILES; PAPER
    • D01—NATURAL OR MAN-MADE THREADS OR FIBRES; SPINNING
    • D01D—MECHANICAL METHODS OR APPARATUS IN THE MANUFACTURE OF ARTIFICIAL FILAMENTS, THREADS, FIBRES, BRISTLES OR RIBBONS
    • D01D5/00—Formation of filaments, threads, or the like
    • D01D5/0007—Electro-spinning
    • D01D5/0015—Electro-spinning characterised by the initial state of the material
    • D01D5/003—Electro-spinning characterised by the initial state of the material the material being a polymer solution or dispersion
    • D01D5/0038—Electro-spinning characterised by the initial state of the material the material being a polymer solution or dispersion the fibre formed by solvent evaporation, i.e. dry electro-spinning
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/12—Cyclic peptides, e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C
    • A61K38/13—Cyclosporins
    • 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
    • A61K9/48—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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection

Abstract

The invention provides a preparation method for preparing cyclosporine solid dispersion based on an electrostatic spinning technology, and relates to the technical field of pharmaceutical preparations. The preparation method comprises the steps of dissolving cyclosporine and polyvinylpyrrolidone in ethanol, preparing a cyclosporine solid dispersion through electrostatic spinning spraying, preparing cyclosporine pellets through extrusion and spheronization based on the cyclosporine solid dispersion, and finally preparing capsules through filling. The invention overcomes the defects of the prior art, prepares the cyclosporine solid dispersion based on the electrostatic spinning technology, has stable process, can well play a role in solubilization, has stable drug release within 1h, has no phenomenon of difficult dissolution, and can achieve good dissolution and bioavailability in vivo and in vitro.

Description

Method for preparing cyclosporine solid dispersion based on electrostatic spinning technology
Technical Field
The invention relates to the technical field of pharmaceutical preparations, in particular to a method for preparing a cyclosporine solid dispersion based on an electrostatic spinning technology.
Background
Cyclosporin (CA), also known as cyclosporin A, is a cyclic polypeptide consisting of 11 amino acids (the structural formula is shown in FIG. 8) and is a cyclic peptide isolated from a culture broth of a filamentous fungus. Belongs to a third-generation high-efficiency and strong-efficiency immunosuppressant. Clinically, the composition is mainly used for anti-rejection reaction of liver, kidney and heart transplantation, and can be used together with adrenocortical hormone to treat immune diseases.
The main formulation of CA at present comprises injection, oral liquid and soft capsule (both RLD/RS), which are approved by FDA in 1990Is the first oral formulation of CA and is recognized as the first peptide oral dosage form. Nohua corporation of 1995 developed and approved improved products for CA->(oral liquid and soft capsule).
CA has the problem of low bioavailability in clinical application, and the main reason is that CA is a poorly soluble drug and has poor dissolution property, so that the bioavailability of the drug is low. A large amount of polyoxyethylene castor oil (Cremophor EL) serving as a solubilizer is added into a CA preparation clinically used at present, so that cholestasis, anaphylactic reaction, hepatorenal toxicity and the like are easily caused.
Oral CA has low bioavailability for a number of main reasons including: (1) The highly regular ring structure of CA results in poor water solubility and intestinal permeability; (2) The presence of P-glycoprotein on the cell membrane enables energy-dependent pumping of CA out of the cell; (3) first pass effect of liver.
The solid dispersion technique refers to a technique in which a poorly soluble drug is uniformly dispersed in a solid carrier material in the form of fine particles, crystallites, or a molecular state. The solid dispersion technology is characterized in that the solubility and dissolution rate of the insoluble medicine are improved and the dissolution and absorption of the medicine are promoted by increasing the specific surface area of the medicine, inhibiting the aggregation and crystallization of the medicine and the like. Common carriers for solid dispersions are polyvinylpyrrolidone, polyethylene glycol (PEG), trimethylchitosan (TMC), and the like.
The cyclosporine solid dispersion can effectively improve the solubility of the drug, and the prior industrialized production technology adopts a high-temperature mode for preparing the cyclosporine solid dispersion, for example, a cyclosporine solid dispersion and a tablet preparation method thereof disclosed in patent number CN202110495284.6 are adopted to prepare the solid dispersion by adopting a hot-melt extrusion method; the "cyclosporin a solid dispersion and the preparation method thereof" disclosed in patent No. CN200410016445.5 are to prepare the cyclosporin a solid dispersion by solvent method, solvent-melting method, grinding method, spray drying method, and freeze drying method, respectively, and although a drug with good solubility can be obtained, the whole preparation process is complicated and drug loss is easily caused.
The electrostatic spinning technology is polymer jet electrostatic stretching spinning method. The basic principle (as shown in fig. 9) is to apply high-voltage static electricity of thousands to tens of thousands of volts to a polymer solution or melt, and the charged polymer droplets are accelerated at the Taylor cone apex of a capillary under the action of an electric field force. When the electric field force is large enough, the polymer droplets overcome the surface tension to form a jet of thin fluid. The trickles evaporate or solidify the solvent during the spraying process and eventually fall onto the receiving means to form a fibrous mat resembling a nonwoven fabric. The polymer solution or molten polymer can be spun into filaments by this method, which was originally created by Forrnhals in 1934, which can be 100-fold reduced in diameter, typically hundreds of nanometers to several micrometers, compared to conventional spinning methods such as dry, wet or melt spinning, etc. Because the electrostatic spinning process is operated under the conditions of no water and low temperature, and no surfactant or emulsifier is added, the preparation method is expected to greatly promote the activity maintenance of protein and peptide drugs in the preparation process.
The electrostatic spinning technology is also applied in the biomedical field, mainly adopts the electrostatic spinning technology to realize ideal encapsulation and loading of various medicines, plays roles of good anticancer, anti-infection, cell differentiation induction and the like by adjusting the release of the medicines by the bracket, namely achieves the aim of slow release of the medicines by the electrostatic spinning technology, and more application solutions of the electrostatic spinning technology in the medicine preparation field are used at the present stage, but the prior literature does not disclose the solubilization research of the electrostatic spinning for insoluble medicines so far.
Disclosure of Invention
Aiming at the defects of the prior art, the invention provides a method for preparing a Cyclosporine Solid Dispersion (CSD) based on an electrostatic spinning technology, which is used for preparing CSD based on the electrostatic spinning technology and further preparing cyclosporine solid dispersion pellets (CSP), and the process is stable, can well solubilize CA, has stable drug release within 1h, has no difficult dissolution phenomenon, and can achieve good dissolution and bioavailability in vivo and in vitro.
In order to achieve the above object, the technical scheme of the present invention is realized by the following technical scheme:
a method for preparing a cyclosporine solid dispersion based on an electrospinning technique, the method comprising the steps of:
(1) Mixing and dissolving: mixing cyclosporine and polyvinylpyrrolidone in ethanol solution, stirring and dissolving to obtain mixed solution for standby;
(2) And (3) electrostatic spinning: carrying out electrostatic spinning treatment on the mixed solution by adopting an electrostatic spinning instrument to obtain a cyclosporine solid dispersion for standby;
(3) Preparing micropill: mixing the cyclosporine solid dispersion with a diluent for granulating, and preparing cyclosporine solid dispersion pellets by an extrusion spheronization mode;
(4) And (3) preparation of capsules: and (3) preparing the cyclosporine solid dispersion pellets into capsules by filling.
Preferably, the weight ratio of the cyclosporine to the polyvinylpyrrolidone in the step (1) is (35-65) (65-35).
Preferably, the polyvinylpyrrolidone model comprises K15, K30, K60, K90, VA64.
Preferably, the working voltage of the electrostatic spinning in the step (2) is 0-20 kV, the solution flow is 0.1-2.2 mL/min, the receiving distance is 1-23 cm, the solution concentration is 15-45%, the working environment temperature is 10-30 ℃, and the relative humidity is 30-60%.
Preferably, the diluent in the step (3) includes a disintegrant and a binder.
Preferably, the disintegrating agent comprises any one or a mixture of any plurality of dry starch and derivatives thereof, hydroxypropyl starch, sodium carboxymethyl starch, low-substituted-hydroxypropyl cellulose, carboxymethyl cellulose calcium, crospovidone, sodium alginate and other salts of alginic acid, surfactants and effervescent disintegrating agents.
Preferably, the binder comprises any one or a mixture of any plurality of starch slurry, sucrose solution, glucose solution, polyvinyl alcohol, cellulose derivative, povidone, gelatin, polyethylene glycol.
Preferably, the granulating mode in the step (3) is wet granulating, the granulating time is 1-5 min, and the pulp adding proportion is 12% -22%.
Preferably, the extrusion rotational speed of the extrusion spheronization in the step (3) is 5-25 rpm, and the spheronization rotational speed is 300-1700 rpm.
Preferably, the cyclosporine solid dispersion pellets in the step (3) have a particle diameter in the range (D 90 ) And the diameter is 0.202-0.377 mm.
The invention provides a method for preparing cyclosporine solid dispersion based on electrostatic spinning technology, which has the advantages compared with the prior art that:
(1) The CSD is creatively prepared by adopting a mode of combining electrostatic spinning and a solid dispersion principle, a feasible method is provided for keeping the activity of peptide drugs and increasing the bioavailability, CSD is prepared by adopting the method, CSP is further prepared, the process is stable, the solubilization function on CA can be well achieved, the drug release within 1h is stable, the phenomenon of difficult dissolution does not occur, and good dissolution and bioavailability can be achieved in vitro and in vivo.
(2) The CSP product prepared based on the electrostatic spinning technology increases the solubility of CA, avoids the damage to the body caused by using other auxiliary material solubilization technologies, and the electrostatic spinning technology volatilizes the solvent under the action of an electric field and simultaneously maintains the activity of the peptide medicine in the preparation process; meanwhile, the pellet has small granularity (less than 0.5 mm), the gastrointestinal tract transportation is not limited by the closure of the pylorus of the stomach, the gastrointestinal tract extrusion is avoided, the transportation speed is stable, the influence of food is small, and the individual difference of pharmacokinetics is small; finally, the preparation prepared by the invention belongs to multi-unit release, each capsule can be filled with hundreds of thousands of pellets, and each pellet is an independent drug release unit, thereby being beneficial to increasing the bioavailability of the drug and being safer and more effective.
Description of the drawings:
fig. 1 is a CSP (CA: pvp=50:50) SEM image;
FIG. 2 is a graph of diffraction contrast of CSD crystalline forms with different CA and PVP ratios;
FIG. 3 is a graph showing the dissolution comparison of CSP in pH1.0 medium for different CA and PVP ratios;
FIG. 4 is a graph showing the dissolution comparison of CSP in pH4.5 medium at different CA and PVP ratios;
FIG. 5 is a graph showing the dissolution comparison of CSP in pH6.8 medium at different CA and PVP ratios;
FIG. 6 is a graph showing comparison of dissolution of CSP in aqueous medium for different CA and PVP ratios;
fig. 7 is a plot of CSD versus CA at different CA and PVP ratios (n=8) in SD rats;
FIG. 8 is a schematic representation of the chemical structural formula of cyclosporine;
fig. 9 is a schematic diagram of the basic principle of electrospinning.
Detailed Description
For the purpose of making the objects, technical solutions and advantages of the embodiments of the present invention more apparent, the technical solutions in the embodiments of the present invention will be clearly and completely described in the following in conjunction with the embodiments of the present invention, and it is apparent that the described embodiments are some embodiments of the present invention, but not all embodiments. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.
Example 1:
preparation of 25mg size CSP (capsules):
1. prescription information is as follows in table 1:
TABLE 1
2. The preparation method comprises the following steps:
(1) About 300g of CA and about 557g of polyvinylpyrrolidone K30 are dissolved in 900mL of ethanol according to the weight ratio of 35:65, and magnetically stirred for 30min for later use;
(2) The working voltage of the electrostatic spinning instrument is 15kV, the flow rate of the solution is 1.5mL/min, the receiving distance is 17cm, the concentration of the solution is 33%, and the working environment temperature is as follows: 10-30 ℃, relative humidity: 45% -55%, and preparing CSD;
(3) About 75g of sucrose was dissolved in 225g of purified water to prepare a sucrose solution (concentration: 33.3%), about 714g of solid dispersion (about 250g of CA), 658g of microcrystalline cellulose, 52.5g of croscarmellose sodium were weighed and premixed in a wet granulator for 5 minutes, and the sucrose solution was added by spraying to prepare a soft mass, the granulating time was 3 minutes, and the soft mass was prepared into CSP of a suitable particle size by extrusion spheronization, extrusion rotation speed: 15rpm; rotational speed of rounding: 1300rpm, and after fluidized bed drying, CSP was obtained having a particle size range (D 90 ) At 0.276mm.
(4) And (3) filling the CSP into No. 2 capsules according to the weight of 150mg to obtain the medicine.
Example 2:
preparation of CSP (Capsule) of 100mg specification
1. The prescription information is shown in table 2 below:
TABLE 2
2. The preparation method comprises the following steps:
(1) About 600g of CA and about 600g of polyvinylpyrrolidone K30 are dissolved in 2000mL of ethanol according to the weight ratio of 50:50, and magnetically stirred for 80min for later use;
(2) The working voltage of the electrostatic spinning instrument is 15kV, the flow rate of the solution is 2.2mL/min, the receiving distance is 23cm, the concentration of the solution is 30%, and the working environment temperature is as follows: 10-30 ℃, relative humidity: 30% -50%, preparing CSD;
(3) About 75g of sucrose is dissolved in 300g of purified water to prepare a sucrose solution (concentration: 25.0%), about 1000g of solid dispersion (about 500g of CA), 372.5g of microcrystalline cellulose and 52.5g of croscarmellose sodium are weighed and premixed in a wet granulator for 5min, the sucrose solution is added by spraying to prepare a soft material, the granulating time is 5min, the soft material is prepared into CSP with proper particle size by extrusion spheronization, and the extrusion rotating speed is as follows: 25rpm; rotational speed of rounding: 1700rpm, and fluidized bed drying to obtain CSP having a particle size range (D 90 ) At 0.377mm.
(4) And (3) filling the CSP into a No. 0 capsule according to the weight of 300mg to obtain the medicine.
Example 3:
preparation of 25mg size CSP (Capsule)
1. The prescription information is as follows:
TABLE 3 Table 3
2. The preparation method comprises the following steps:
(1) About 300g of CA and about 161.6g of polyvinylpyrrolidone K90 are dissolved in 850mL of ethanol according to the weight ratio of 65:35, and magnetically stirred for 45min for later use;
(2) The working voltage of the electrostatic spinning instrument is 11kV, the flow rate of the solution is 1.3mL/min, the receiving distance is 16cm, the concentration of the solution is 35.3%, and the working environment temperature is as follows: 10-30 ℃, relative humidity: 40% -50%, preparing CSD;
(3) About 60g of glucose was dissolved in 270g of purified water to prepare a glucose solution (concentration: 22.2%), about 384.6g of solid dispersion (about 250g of CA), 544.5g of microcrystalline cellulose, 450.9g of pregelatinized starch, 60g of low-substituted-hydroxypropylcellulose were weighed and premixed in a wet granulator for 7 minutes, the glucose solution was added by spraying to prepare a soft mass, the granulation time was 3 minutes, the soft mass was prepared into CSP of a suitable particle size by extrusion spheronization, and the extrusion speed: 18rpm; rotational speed of rounding: 1500rpm, and after fluidized bed drying, CSP was obtained having a particle size range (D 90 ) At 0.308mm.
(4) And (3) filling the CSP into No. 2 capsules according to the weight of 150mg to obtain the medicine.
Example 4:
preparation of 25mg size CSP (Capsule)
1. The prescription information is shown in table 4 below:
TABLE 4 Table 4
2. The preparation method comprises the following steps:
(1) About 300g of CA and about 300g of polyvinylpyrrolidone K60 are dissolved in 875mL of ethanol according to the weight ratio of 50:50, and magnetically stirred for 45min for later use;
(2) The working voltage of the electrostatic spinning instrument is 18kV, the flow rate of the solution is 1.7mL/min, the receiving distance is 20cm, the concentration of the solution is 34.29%, and the working environment temperature is as follows: 10-30 ℃, relative humidity: 30% -50%, preparing CSD;
(3) About 37.5g of glucose and 37.5g of starch are dissolved in 262.5g of purified water to prepare a glucose and starch solution, about 500g of solid dispersion (about 250g of CA), 456g of microcrystalline cellulose, 409g of lactose, 30g of low-substituted-hydroxypropyl cellulose and 30g of crospovidone are weighed and premixed in a wet granulator for 6min, the glucose and starch solution are added by spraying to prepare a soft material, the granulating time is 4min, the soft material is prepared into pellets with proper particle size by extrusion and spheronization, and the extrusion rotating speed is as follows: 16rpm; rotational speed of rounding: 1000rpm, and dried by fluidized bed to obtain CSP having a particle size range (D 90 ) At 0.325mm.
(4) And (3) filling the CSP into No. 2 capsules according to the weight of 150mg to obtain the medicine.
Example 5:
preparation of CSP (Capsule) of 100mg specification
1. The prescription information is shown in table 5 below:
TABLE 5
2. The preparation method comprises the following steps:
(1) About 1200g CA and about 1200g polyvinylpyrrolidone K60 are dissolved in 7500mL ethanol according to the weight ratio of 50:50, and magnetically stirred for 150min for standby;
(2) The working voltage of the electrostatic spinning instrument is 19kV, the flow rate of the solution is 2.2mL/min, the receiving distance is 22cm, the concentration of the solution is 16%, and the working environment temperature is as follows: 10-30 ℃, relative humidity: 35% -55%, preparing CSD;
(3) About 90g glucose, 60g polyvinyl alcohol were dissolved in 520g purified water to prepare a sucrose solution, and about 2000g solid dispersion (about 1000g CA), 292.5g silicified microcrystalline cellulose, 166.2g pregelatinized starch, 256.5g lactose spray, 45g croscarmellose sodium, 45g calcium carboxymethylcellulose, 45g sodium alginate wet granulator were weighed and pre-mixed for 5min by sprayingAdding sucrose solution, preparing a soft material, granulating for 5min, preparing the soft material into CSP with proper particle size by extrusion and spheronization, and extruding at a rotating speed: 25rpm; rotational speed of rounding: 1150rpm, and after fluidized bed drying, CSP was obtained having a particle size range (D 90 ) At 0.293mm.
(4) And (3) filling the CSP into a No. 0 capsule according to the weight of 300mg to obtain the medicine.
Example 6:
dissolution test: the method and raw materials of example 1 were used to control the weight ratio of CSD: CA: pvp=35:65, 50:50, 65:35, CSP was prepared for dissolution testing with the media selected from: pH1.0, pH4.5, pH6.8, water, stirring mode: the paddle method has the rotating speed of: 100rpm, medium volume: 900mL, sample point set to: 5min, 10min, 15min, 20min, 30min, 45min, 60min, and 90min.
As shown in FIGS. 3 to 6, the CSP prepared by the method has good solubilization and stable prescription process.
Example 7:
pharmacokinetic experiments:
the method and raw materials of example 1 were used to control the weight ratio of CSD: CA: pvp=35:65, 50:50, 65:35, and the prepared CSP was subjected to pharmacokinetic experiments comparing the relative bioavailability of CSD and CA drug substance prepared in different proportions in SD rats;
the experimental process is as follows:
SD rats, males, 32, body weight 240+ -20 g, were randomly divided into 4 groups of 8. The experiment adopts a single administration mode, the administration dose is 60mg/kg, the orbit is used for taking blood, the blood is fasted overnight before administration, plasma samples are immediately extracted at 0.5, 1, 2, 3, 4, 6, 8, 10, 12 and 24 hours respectively, and the blood is collected in a heparin tube. The plasma was subjected to HPLC-MS analysis, and pharmacokinetic parameters are shown in Table 6 and FIG. 7.
Table 6: physical kinetic parameters (Single chamber model)
From the table and the graph, the CSD obviously increases the relative bioavailability of the medicine in vivo, and the higher the CA: PVP proportion is, the better the bioavailability is;
wherein: CA, PVP=35:65, and the relative bioavailability of CSD relative to the bulk drug is 233.62%;
CsA, pvp=50:50, the relative bioavailability of CSD relative to the drug substance was 276.26%;
CsA pvp=65:35, the relative bioavailability of CSD relative to the drug substance was 322.78%.
The above embodiments are only for illustrating the technical solution of the present invention, and are not limiting; although the invention has been described in detail with reference to the foregoing embodiments, it will be understood by those of ordinary skill in the art that: the technical scheme described in the foregoing embodiments can be modified or some technical features thereof can be replaced by equivalents; such modifications and substitutions do not depart from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims (10)

1. A method for preparing a cyclosporine solid dispersion based on an electrospinning technique, characterized in that the method for preparing a cyclosporine solid dispersion comprises the steps of:
(1) Mixing and dissolving: mixing cyclosporine and polyvinylpyrrolidone in ethanol solution, stirring and dissolving to obtain mixed solution for standby;
(2) And (3) electrostatic spinning: carrying out electrostatic spinning treatment on the mixed solution by adopting an electrostatic spinning instrument to obtain a cyclosporine solid dispersion for standby;
(3) Preparing micropill: mixing the cyclosporine solid dispersion with a diluent for granulating, and preparing cyclosporine solid dispersion pellets by an extrusion spheronization mode;
(4) And (3) preparation of capsules: and preparing the cyclosporine solid dispersion pellets into capsules by a capsule filling device.
2. The method for preparing cyclosporine solid dispersion based on electrospinning technique according to claim 1, wherein: the weight ratio of the cyclosporine to the polyvinylpyrrolidone in the step (1) is (35-65) (65-35).
3. The method for preparing cyclosporine solid dispersion based on electrospinning technique according to claim 1, wherein: the polyvinylpyrrolidone model comprises K15, K30, K60, K90 and VA64.
4. The method for preparing cyclosporine solid dispersion based on electrospinning technique according to claim 1, wherein: the working voltage of the electrostatic spinning in the step (2) is 0-20 kV, the solution flow is 0.1-2.2 mL/min, the receiving distance is 1-23 cm, the solution concentration is 15-45%, the working environment temperature is 10-30 ℃, and the relative humidity is 30-60%.
5. The method for preparing cyclosporine solid dispersion based on electrospinning technique according to claim 1, wherein: the diluent in the step (3) comprises a disintegrating agent and a binder.
6. The method for preparing cyclosporine solid dispersion based on electrospinning technique according to claim 5, wherein: the disintegrating agent comprises one or a mixture of more of dry starch and derivatives thereof, hydroxypropyl starch, sodium carboxymethyl starch, low-substituted-hydroxypropyl cellulose, carboxymethyl cellulose calcium, crospovidone, sodium alginate and other salts of alginic acid, surfactants and effervescent disintegrating agents.
7. The method for preparing cyclosporine solid dispersion based on electrospinning technique according to claim 5, wherein: the binder comprises any one or a mixture of any more of starch slurry, sucrose solution, glucose solution, polyvinyl alcohol, cellulose derivative, povidone, gelatin and polyethylene glycol.
8. The method for preparing the cyclosporine solid dispersion based on the electrospinning technology according to claim 1, wherein the granulating mode in the step (3) is wet granulating, the granulating time is 1-5 min, and the pulping proportion is 12% -22%.
9. The method for preparing a cyclosporine solid dispersion based on the electrospinning technique according to claim 1, wherein the extrusion rotation speed of the extrusion spheronization in the step (3) is 5 to 25rpm, and the spheronization rotation speed is 300 to 1700rpm.
10. The method for preparing a cyclosporine solid dispersion based on the electrospinning technique according to claim 1, wherein the particle diameter range (D 90 ) And the diameter is 0.202-0.377 mm.
CN202310856811.0A 2023-07-12 2023-07-12 Method for preparing cyclosporine solid dispersion based on electrostatic spinning technology Pending CN116898820A (en)

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Inventor after: Liu Hongbin

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Inventor after: Xu Chongli

Inventor after: Ma Zheng

Inventor after: Huang Zhimin

Inventor before: Liu Hongbin

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