CN114557982A - Perampanel electrospun fiber oral instant film agent and preparation method thereof - Google Patents
Perampanel electrospun fiber oral instant film agent and preparation method thereof Download PDFInfo
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- CN114557982A CN114557982A CN202210359851.XA CN202210359851A CN114557982A CN 114557982 A CN114557982 A CN 114557982A CN 202210359851 A CN202210359851 A CN 202210359851A CN 114557982 A CN114557982 A CN 114557982A
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- PRMWGUBFXWROHD-UHFFFAOYSA-N perampanel Chemical compound O=C1C(C=2C(=CC=CC=2)C#N)=CC(C=2N=CC=CC=2)=CN1C1=CC=CC=C1 PRMWGUBFXWROHD-UHFFFAOYSA-N 0.000 title claims abstract description 79
- 229960005198 perampanel Drugs 0.000 title claims abstract description 78
- 239000000835 fiber Substances 0.000 title claims abstract description 67
- 239000003795 chemical substances by application Substances 0.000 title claims abstract description 59
- 238000002360 preparation method Methods 0.000 title claims abstract description 20
- 239000000463 material Substances 0.000 claims abstract description 33
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims abstract description 30
- 239000003814 drug Substances 0.000 claims abstract description 26
- 229920003171 Poly (ethylene oxide) Polymers 0.000 claims abstract description 21
- 239000004480 active ingredient Substances 0.000 claims abstract description 18
- 229920003169 water-soluble polymer Polymers 0.000 claims abstract description 17
- 238000010041 electrostatic spinning Methods 0.000 claims abstract description 16
- 238000000034 method Methods 0.000 claims abstract description 14
- -1 polyoxyethylene Polymers 0.000 claims abstract description 14
- 239000011159 matrix material Substances 0.000 claims abstract description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 8
- 238000009987 spinning Methods 0.000 claims description 16
- 238000003756 stirring Methods 0.000 claims description 12
- 239000008186 active pharmaceutical agent Substances 0.000 claims description 7
- 239000002994 raw material Substances 0.000 claims description 7
- 239000000758 substrate Substances 0.000 claims description 7
- 238000001035 drying Methods 0.000 claims description 6
- 238000007872 degassing Methods 0.000 claims description 5
- 239000000796 flavoring agent Substances 0.000 claims description 5
- 235000013355 food flavoring agent Nutrition 0.000 claims description 4
- 239000003086 colorant Substances 0.000 claims description 3
- 239000006068 taste-masking agent Substances 0.000 claims description 3
- 239000000654 additive Substances 0.000 claims 1
- 230000000996 additive effect Effects 0.000 claims 1
- 229940079593 drug Drugs 0.000 abstract description 9
- 239000002552 dosage form Substances 0.000 abstract description 3
- 210000000214 mouth Anatomy 0.000 abstract description 3
- 239000000825 pharmaceutical preparation Substances 0.000 abstract description 2
- 239000000243 solution Substances 0.000 description 27
- 239000002904 solvent Substances 0.000 description 10
- 206010015037 epilepsy Diseases 0.000 description 5
- 238000004090 dissolution Methods 0.000 description 3
- 238000002329 infrared spectrum Methods 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 239000000049 pigment Substances 0.000 description 3
- UUDAMDVQRQNNHZ-UHFFFAOYSA-N (S)-AMPA Chemical compound CC=1ONC(=O)C=1CC(N)C(O)=O UUDAMDVQRQNNHZ-UHFFFAOYSA-N 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 239000001961 anticonvulsive agent Substances 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 239000000651 prodrug Substances 0.000 description 2
- 229940002612 prodrug Drugs 0.000 description 2
- 210000002784 stomach Anatomy 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 230000009747 swallowing Effects 0.000 description 2
- 235000011437 Amygdalus communis Nutrition 0.000 description 1
- 206010010904 Convulsion Diseases 0.000 description 1
- 208000019505 Deglutition disease Diseases 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- CWRVKFFCRWGWCS-UHFFFAOYSA-N Pentrazole Chemical compound C1CCCCC2=NN=NN21 CWRVKFFCRWGWCS-UHFFFAOYSA-N 0.000 description 1
- 241000220304 Prunus dulcis Species 0.000 description 1
- 238000002441 X-ray diffraction Methods 0.000 description 1
- 235000020224 almond Nutrition 0.000 description 1
- 230000003556 anti-epileptic effect Effects 0.000 description 1
- 229960003965 antiepileptics Drugs 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000007922 dissolution test Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000011705 epilepsy animal model Methods 0.000 description 1
- 238000010579 first pass effect Methods 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 230000000873 masking effect Effects 0.000 description 1
- 239000013081 microcrystal Substances 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 210000002200 mouth mucosa Anatomy 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 231100000989 no adverse effect Toxicity 0.000 description 1
- 229940125946 non-competitive receptor antagonist Drugs 0.000 description 1
- 239000004014 plasticizer Substances 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 208000020016 psychiatric disease Diseases 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 210000003296 saliva Anatomy 0.000 description 1
- 238000000935 solvent evaporation Methods 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
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- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/444—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
-
- 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
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
-
- 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
- A61K9/006—Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/08—Antiepileptics; Anticonvulsants
-
- 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
-
- 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
-
- 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
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
- A61K9/7007—Drug-containing films, membranes or sheets
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Abstract
A Perampanel electrospun fiber oral instant film agent and a preparation method thereof belong to the field of pharmaceutical preparations. The Perampanel electrospun fiber oral instant film agent comprises the following components: active components of medicine, and water soluble polymer film forming material. The active ingredient of the medicine is Perampanel or derivatives thereof, and the water-soluble polymer film-forming material is polyoxyethylene. The preparation method comprises dissolving the active ingredients in acetonitrile to obtain a film-forming matrix solution, adding water-soluble polymer film-forming material, and performing electrostatic spinning. The method endows the Perampanel electrospun fiber oral instant film agent with extremely high specific surface area, and enables the medicine to be in an amorphous state. The oral instant film agent is simple to prepare, has excellent mechanical properties, and can be completely dissolved in water within 3 s. The ideal stability and uniformity are achieved, the medication requirements of specific patients are met, and the blank of the oral cavity instant film dosage form of the Perampanel on the market is filled.
Description
Technical Field
The invention belongs to the field of pharmaceutical preparations, and particularly relates to a Perampanel electrospun fiber oral instant film agent and a preparation method thereof.
Background
Perampanel is a third generation of novel antiepileptic drug approved by the U.S. FDA for marketing in 2012 and used to treat patients 12 years old and older with partial seizure epilepsy. Perampanel acts on alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) type glutamic acid receptors, is a highly selective non-competitive receptor antagonist, has a wide antiepileptic spectrum, and is effective on various epilepsy animal models including MES-induced epilepsy, 6Hz epilepsy, pentylenetetrazol-induced epilepsy and almond kernel ignition model. Perampanel existing in the market only has two dosage forms, namely a tablet and a suspension, and both adopt Perampanel microcrystal as a raw material. Because the Perampanel is a poorly soluble drug, the microcrystalline solubility is poor, and the bioavailability is low. For some specific people, such as the elderly, children with mental illness and patients with dysphagia caused by other factors, the tablet is obviously not suitable for taking, and the suspension has the problems of property stability and inconvenience in carrying and using. Therefore, there is an urgent need to develop a novel formulation to meet the clinical needs of patients.
The oral instant film agent is a film preparation prepared by processing raw material medicines and proper film-forming materials and is used for oral administration or mucous membrane. Has the following advantages, such as: 1) the dosage is accurate; 2) is convenient to carry and store; 3) the property is stable; 4) the process is simple; 5) after being taken, the medicine can be dissolved and released quickly, and a part of the medicine can directly enter blood circulation through oral mucosa, so that the first pass effect and the like are avoided. Most of the existing oral instant film agents adopt a solvent evaporation method, namely, a solvent is adopted to dissolve raw material medicaments and film-forming polymers, and then a film is coated and the solvent is volatilized to obtain a flaky film agent. Although the method is simple and convenient, the solvent volatilization process is longer, the medicine is easy to crystallize, and the bioavailability of the slightly soluble medicine can be reduced.
Disclosure of Invention
The invention aims to provide a Perampanel electrospun fiber oral instant film agent and a preparation method thereof, which are used for treating epilepsy. The Perampanel electrospun fiber oral instant film agent is endowed with extremely high specific surface area through an electrostatic spinning method, and the medicine is in an amorphous state. The oral instant film agent is simple to prepare, has excellent mechanical properties, and can be completely dissolved in water within 3 s. The ideal stability and uniformity are achieved, the medication requirements of specific patients are met, and the blank of the oral cavity instant film dosage form of the Perampanel on the market is filled.
In order to achieve the purpose, the technical scheme adopted by the invention is as follows:
the invention relates to a Perampanel electrospun fiber oral instant film agent, which comprises the following components: active components of medicine, water soluble high molecular filming material.
Furthermore, the active ingredients of the medicine account for 5 to 20 percent of the Perampanel electrospun fiber oral instant film agent by mass percent.
The active pharmaceutical ingredient is Perampanel or derivatives thereof.
The water-soluble polymer film-forming material is preferably polyoxyethylene, and more preferably polyoxyethylene with the weight-average molecular weight of 100000-300000.
The Perampanel electrospun fiber oral instant film agent has the tensile strength of 1.01 +/-0.25 MPa, the elongation of 128 +/-11 percent and the specific surface area of 52 +/-4 m2/g。
The Perampanel electrospun fiber oral instant film agent can be completely dissolved in water within 3s, and the crystal form of Perampanel in the film agent is amorphous.
The Perampanel electrospun fiber oral instant film agent disclosed by the invention can also comprise optional common flavoring agents and flavor masking auxiliary materials in the field, such as sucrose and the like, in order to improve the mouthfeel, and the addition amount of the Perampanel electrospun fiber oral instant film agent is 1-5% of the weight of the film.
The Perampanel electrospun fiber oral instant film agent disclosed by the invention can also comprise optional common colorant auxiliary materials in the field, such as edible pigment and the like, in order to improve the appearance, and the addition amount of the Perampanel electrospun fiber oral instant film agent is 1-5% of the weight of the film.
The invention discloses a preparation method of a Perampanel electrospun fiber oral instant film agent, which comprises the following steps:
(1) dissolving the active ingredients of the medicine in acetonitrile, stirring and dissolving to obtain a film forming matrix solution;
(2) adding a water-soluble polymer film-forming material into a film-forming matrix solution, uniformly stirring and fully dissolving, defoaming and degassing to obtain a spinning solution;
(3) and (3) taking the spinning solution as a raw material, carrying out electrostatic spinning, drying and demoulding to obtain the Perampanel electrospun fiber oral instant film agent.
In the step (1), the mass percentage of the active pharmaceutical ingredients in the film-forming matrix solution is 0.3-1.1%.
In the step (2), the water-soluble polymer film-forming material accounts for 4-10% of the spinning solution by mass.
In the step (2), ultrasonic is adopted for defoaming, the ultrasonic frequency is 25-40 KHz, and the ultrasonic time is 20-30 s.
In the step (3), the electrostatic spinning process parameters are as follows: the voltage is 7-10 kV, the flow rate is 0.40-0.70 mL/h, and the distance between the needle head and the receiver is 10 cm.
In the step (3), the drying and demolding process comprises the following steps: vacuum drying for 4-24 h at room temperature-40 ℃.
The Perampanel electrospun fiber oral instant film agent and the preparation method thereof have the beneficial effects that:
1. the electrostatic spinning method used by the invention has simple process, the prepared fiber membrane has extremely large specific surface area and excellent mechanical property, the drug loading rate of the fiber network is high, loose and porous, and particularly for preparing insoluble drugs, the insoluble drugs can be quickly dissolved after being orally taken and enter the stomach along with saliva to be absorbed, so that swallowing is avoided, the compliance of patients is greatly improved, and the problem of difficult medicine taking of patients with difficult swallowing caused by some special patients, such as old people, children and other factors, is solved.
2. The nanometer fiber membrane with extremely high specific surface area and porosity can be obtained by controlling the adding sequence of the raw materials and the electrostatic spinning process, the dissolution is fast, the loaded insoluble drug exists in amorphous state in the fiber, and the bioavailability is high.
3. The solvent adopted by the invention is acetonitrile, which can dissolve the active ingredient of Perampanel, so that the problems of poor water solubility and insolubility in water are solved, and the acetonitrile can also dissolve the water-soluble high-molecular film-forming material, and after subsequent electrostatic spinning and drying and demoulding, the water-soluble high-molecular film-forming material can be quickly removed without residue.
4. The water-soluble high-molecular film-forming material polyoxyethylene has a large molecular weight, so that the water-soluble high-molecular film-forming material polyoxyethylene is difficult to absorb by intestines and stomach, no adverse effect is caused to a human body when the water-soluble high-molecular film-forming material is orally taken, the flexibility of the film agent prepared by single use is good, and the film agent with good mechanical property under the condition of high drug-loading capacity can be obtained.
5. The oral instant film agent does not contain plasticizer or solubilizer, and can also achieve the effect of good film body flexibility.
Drawings
FIG. 1 is a fiber morphology chart of a Perampanel electrospun fiber oral instant film agent;
FIG. 2 is a mechanical drawing of a Perampanel electrospun fiber oral instant film;
FIG. 3 is a dissolution profile of a Perampanel electrospun fiber oral instant film in 0.1mol/L HCl (paddle method, 50 rpm);
FIG. 4 is an X-ray diffraction pattern of a Perampanel prodrug, a Perampanel electrospun fiber oral instant film and polyethylene oxide (PEO);
fig. 5 is an infrared spectrum of a perampanel prodrug, a perampanel electrospun fiber oral instant film agent, and polyethylene oxide (PEO).
Detailed Description
The following examples further illustrate the technical solution of the present invention. It is to be understood that the described embodiments are merely provided to assist in understanding the invention and are not intended to be exhaustive or to limit the invention.
In the following examples, reagents and equipment used were commercially available unless otherwise specified.
Example 1
In the embodiment, the Perampanel is used as a pharmaceutical active ingredient to prepare the Perampanel electrospun fiber oral instant film agent, which can be used for oral administration, and the implementation adopted raw materials are as follows:
the polyethylene oxide of this example had a weight average molecular weight of 20 ten thousand.
A preparation method of a Perampanel electrospun fiber oral instant film agent comprises the following steps:
(1) dissolving Perampanel in acetonitrile solvent, and stirring to fully dissolve the Perampanel to obtain a film forming matrix solution; wherein, the Perampanel accounts for 1 percent of the mass of the film forming substrate solution;
(2) adding polyoxyethylene into the film-forming substrate solution obtained in the step (1), continuously stirring to fully dissolve, and then ultrasonically defoaming and degassing to obtain a spinning solution;
(3) injecting the treated spinning solution into electrostatic spinning equipment, adjusting parameters of the electrostatic spinning equipment (voltage 8kV and flow rate 0.60mL/h), starting preparation, collecting a fiber membrane (the distance between a needle head and the receiver is 10cm), drying in vacuum at 40 ℃ for 4h, and demolding to obtain the Perampanel electrospun fiber oral instant film agent, wherein the fiber morphology is shown in figure 1, and from figure 1, the fiber diameter is about 500nm, the surface is smooth, and no droplet is generated.
The Perampanel electrospun fiber oral instant film prepared according to the formula and the preparation method is smooth in appearance, and the Perampanel is in an amorphous state in the fiber (figure 4). The oral instant film agent of the Perampanel electrospun fiber has good mechanical performance indexes such as tensile strength and elongation, wherein the tensile strength of the oral instant film agent of the Perampanel electrospun fiber is 1.02MPa, and the elongation is 132% (see figure 2). Dissolution tests show that the Perampanel electrospun fiber oral instant film agent is dissolved out for more than 85% in 15min (figure 3), and shows great application potential of the invention.
The infrared spectrogram of the technical piranpa, the oral instant film of the piranpa electrospun fiber and polyethylene oxide (PEO) is shown in figure 5, and the infrared spectrum of the oral instant film of the piranpa electrospun fiber can show that the characteristic peak of the piranpa occurs in the infrared spectrum of the oral instant film of the piranpa electrospun fiber from figure 5, which indicates that the drug is loaded in the fiber.
Example 2
The oral instant film agent of the Perampanel electrospun fiber comprises the following components: the composition comprises a pharmaceutical active ingredient and a water-soluble polymer film-forming material, wherein the pharmaceutical active ingredient is Perampanel, and the water-soluble polymer film-forming material is polyoxyethylene. The oral instant film agent is prepared by the steps of spinning solution preparation, electrostatic spinning, drying and demoulding and the like.
Wherein the weight of the active pharmaceutical ingredients accounts for 5 percent of the dry weight of the Perampanel electrospun fiber oral instant film agent, and the balance is a water-soluble polymer film-forming material.
The embodiment also provides a preparation method of the Perampanel electrospun fiber oral instant film agent, which comprises the following steps:
(1) dissolving the active ingredients of the medicine in acetonitrile solvent, stirring to fully dissolve the active ingredients to obtain a film forming substrate solution; wherein, the mass percent of the active ingredients of the medicine accounts for 0.3 percent of the film forming matrix solution.
(2) Adding a water-soluble polymer film-forming material into the film-forming matrix solution obtained in the step (1), continuously stirring to fully dissolve, and performing ultrasonic defoaming and degassing to obtain a spinning solution; wherein the mass percent of the water-soluble polymer film-forming material spinning solution is 5 percent;
(3) and injecting the treated spinning solution into electrostatic spinning equipment, adjusting parameters of the electrostatic spinning equipment, starting preparation, and collecting a film agent on the surface of a receiver.
Example 3
The Perampanel electrospun fiber oral instant film agent comprises the following components: the composition comprises a pharmaceutical active ingredient and a water-soluble polymer film-forming material, wherein the pharmaceutical active ingredient is a derivative of Perampanel, and the water-soluble polymer film-forming material is polyoxyethylene;
in the embodiment, the weight average molecular weight of the polyoxyethylene is 100000-300000;
in this example, in order to improve the mouth feel, a flavoring agent and a taste masking agent auxiliary material which are optionally commonly used in the field are added into the Perampanel electrospun fiber oral instant film, sucrose is added in this example, and the addition mass is 2% of the film weight.
In this embodiment, in order to improve the appearance, a colorant auxiliary material optionally commonly used in the field is added into the Perampanel electrospun fiber oral instant film, and in this embodiment, an edible pigment is added, and the mass of the added pigment is 1% of the weight of the film.
The preparation method of the Perampanel electrospun fiber oral instant film agent comprises the following steps:
(1) dissolving the active ingredients of the medicine in acetonitrile solvent, stirring to fully dissolve the active ingredients to obtain a film forming substrate solution;
(2) adding polyoxyethylene into the film-forming substrate solution obtained in the step (1), continuously stirring to fully dissolve, and performing ultrasonic defoaming and degassing to obtain a spinning solution;
(3) and injecting the treated spinning solution into electrostatic spinning equipment, adjusting parameters of the electrostatic spinning equipment, starting preparation, and collecting a film agent on the surface of a receiver.
Comparative example 1
The difference from example 1 is that:
the mixed solution of acetonitrile and water is used as a solvent, so that the perampanel is slowly dissolved, even partially dissolved, and a uniform spinning solution cannot be obtained.
Comparative example 2
The difference from example 1 is that:
(1) dissolving water-soluble high-molecular film-forming material polyoxyethylene in acetonitrile solvent, and stirring to fully dissolve to obtain film-forming substrate solution;
(2) and (2) adding the active pharmaceutical ingredients into the film-forming matrix solution obtained in the step (1), and continuously stirring to fully dissolve the active pharmaceutical ingredients to obtain a spinning solution.
Compared with example 1, the water-soluble polymer film-forming material has a certain viscosity after being dissolved, so that the first: perampanel has long dissolution time, and secondly: perampanel is not uniformly dispersed.
Claims (10)
1. The Perampanel electrospun fiber oral instant film agent is characterized by comprising the following components: a pharmaceutically active ingredient, a water-soluble polymer film-forming material; the active pharmaceutical ingredient is Perampanel or derivatives thereof; the water-soluble high-molecular film-forming material is polyoxyethylene.
2. The perampanel electrospun fiber oral instant film agent according to claim 1, wherein the pharmaceutical active ingredient accounts for 5-20% of the perampanel electrospun fiber oral instant film agent by mass.
3. The Perampanel electrospun fiber oral instant film agent according to claim 1, wherein the polyoxyethylene is polyoxyethylene with a weight average molecular weight of 100000-300000.
4. The perampanel electrospun fiber oral instant film agent according to claim 1, further comprising a flavoring agent and a taste masking agent auxiliary material which are optionally commonly used in the field, wherein the addition amount of the flavoring agent and the taste masking agent auxiliary material is 1-5% of the film weight;
and/or the Perampanel electrospun fiber oral instant film agent further comprises optional common colorant auxiliary materials in the field, and the addition amount of the additive is 1-5% of the film weight.
5. The perampanel electrospun fiber oral instant film agent according to any one of claims 1 to 4, wherein the tensile strength of the perampanel electrospun fiber oral instant film agent is 1.01 +/-0.25 MPa, the elongation is 128 +/-11%, and the specific surface area is 52 +/-4 m2/g。
6. The Perampanel electrospun fiber oral instant film agent according to any one of claims 1-4, wherein the Perampanel electrospun fiber oral instant film agent is completely dissolved in water within 3s, and the crystalline form of Perampanel in the Perampanel electrospun fiber oral instant film agent is amorphous.
7. The preparation method of the Perampanel electrospun fiber oral instant film agent as claimed in any one of claims 1-4, characterized by comprising the following steps:
(1) dissolving the active ingredients of the medicine in acetonitrile, stirring and dissolving to obtain a film forming matrix solution;
(2) adding a water-soluble polymer film-forming material into a film-forming substrate solution, uniformly stirring and fully dissolving, defoaming and degassing to obtain a spinning solution;
(3) and (3) carrying out electrostatic spinning by using the spinning solution as a raw material, and then drying and demoulding to obtain the Perampanel electrospun fiber oral instant film agent.
8. The preparation method of the Perampanel electrospun fiber oral instant film agent according to claim 7, wherein in the step (1), the mass percentage of the active pharmaceutical ingredient in the film forming matrix solution is 0.3-1.1%.
9. The preparation method of the Perampanel electrospun fiber oral instant film agent according to claim 7, wherein in the step (2), the water-soluble polymer film forming material accounts for 4-10% of the spinning solution by mass.
10. The method for preparing the Perampanel electrospun fiber oral instant film according to claim 7, wherein in the step (3), the electrostatic spinning process parameters are as follows: the voltage is 7-10 kV, the flow rate is 0.40-0.70 mL/h, and the distance between the needle head and the receiver is 10 cm.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN116617193A (en) * | 2023-07-10 | 2023-08-22 | 北京丰科睿泰医药科技有限公司 | Pirenpananel oral film-dissolving agent |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20030017208A1 (en) * | 2002-07-19 | 2003-01-23 | Francis Ignatious | Electrospun pharmaceutical compositions |
| CN101570917A (en) * | 2009-06-03 | 2009-11-04 | 东华大学 | Method for preparing bio-adhesive medicament-carrying nano-fiber membrane by electro-spinning |
| CN109106696A (en) * | 2018-09-25 | 2019-01-01 | 北京普瑞博思投资有限公司 | Lun Panai mouthfuls of molten films of pyrrole and preparation method thereof |
| CN109730978A (en) * | 2019-01-23 | 2019-05-10 | 沈阳药科大学 | A kind of oral quick-dissolving film preparation and preparation method thereof containing Lizakuputan benzoate |
| CN109730980A (en) * | 2019-03-05 | 2019-05-10 | 深圳市新阳唯康科技有限公司 | One kind containing multi-component naringenin mucous membrane of mouth agent and preparation method thereof |
| CN112999403A (en) * | 2021-03-01 | 2021-06-22 | 中国科学院烟台海岸带研究所 | Preparation method of oral cavity repairing film |
-
2022
- 2022-04-07 CN CN202210359851.XA patent/CN114557982A/en active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20030017208A1 (en) * | 2002-07-19 | 2003-01-23 | Francis Ignatious | Electrospun pharmaceutical compositions |
| CN101570917A (en) * | 2009-06-03 | 2009-11-04 | 东华大学 | Method for preparing bio-adhesive medicament-carrying nano-fiber membrane by electro-spinning |
| CN109106696A (en) * | 2018-09-25 | 2019-01-01 | 北京普瑞博思投资有限公司 | Lun Panai mouthfuls of molten films of pyrrole and preparation method thereof |
| CN109730978A (en) * | 2019-01-23 | 2019-05-10 | 沈阳药科大学 | A kind of oral quick-dissolving film preparation and preparation method thereof containing Lizakuputan benzoate |
| CN109730980A (en) * | 2019-03-05 | 2019-05-10 | 深圳市新阳唯康科技有限公司 | One kind containing multi-component naringenin mucous membrane of mouth agent and preparation method thereof |
| CN112999403A (en) * | 2021-03-01 | 2021-06-22 | 中国科学院烟台海岸带研究所 | Preparation method of oral cavity repairing film |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN116617193A (en) * | 2023-07-10 | 2023-08-22 | 北京丰科睿泰医药科技有限公司 | Pirenpananel oral film-dissolving agent |
| CN116617193B (en) * | 2023-07-10 | 2024-01-30 | 北京丰科睿泰医药科技有限公司 | Pirenpananel oral film-dissolving agent |
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