CN114522166B - Solid dispersion composition and preparation method and application thereof - Google Patents
Solid dispersion composition and preparation method and application thereof Download PDFInfo
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- CN114522166B CN114522166B CN202210427678.2A CN202210427678A CN114522166B CN 114522166 B CN114522166 B CN 114522166B CN 202210427678 A CN202210427678 A CN 202210427678A CN 114522166 B CN114522166 B CN 114522166B
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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
- A61K31/47—Quinolines; Isoquinolines
- A61K31/485—Morphinan derivatives, e.g. morphine, codeine
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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
- A61K31/47—Quinolines; Isoquinolines
- A61K31/49—Cinchonan derivatives, e.g. quinine
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
- A61K9/145—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic compounds
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
- A61K9/146—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic macromolecular compounds
-
- 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
-
- 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
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
Abstract
The invention discloses a dextromethorphan quinidine solid dispersion composition, a preparation method and application thereof. By adding a proper high molecular carrier and a pore-forming agent, the prepared dextromethorphan solid dispersion and quinidine solid dispersion are basically insoluble in the oral cavity and have good dissolution effect in a gastric juice environment, and the technical effect of good taste-modifying effect of dextromethorphan and quinidine while meeting the dissolution requirement of the medicine is achieved. The dextromethorphan quinidine solid composition is easy to prepare into various oral preparations which are easy to swallow, solves the problem of dysphagia of patients with nervous system diseases, and can greatly improve the medication experience.
Description
Technical Field
The invention relates to the field of pharmaceutical preparations, in particular to a composition containing dextromethorphan solid dispersion and quinidine solid dispersion, and a preparation method and application thereof.
Background
Dextromethorphan hydrobromide and quinidine sulfate are compound drugs developed by Avanir pharmaceuticals Inc to treat pseudobulbar mood (PBA), and are first approved by the FDA to be marketed in 10 months in 2010. The drug is the first and only one drug for treating PBA, also known as emotional incontinence, which is mainly secondary to neurological diseases such as parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis, and stroke, and is characterized by the sudden appearance of involuntary crying or laughing.
Dextromethorphan and quinidine have poor taste and are bitter and numb, and the currently marketed dosage form is a capsule. Patients with nervous system diseases are often accompanied by dysphagia, salivation and other symptoms. Studies have shown that patients with Parkinson's disease have an incidence of dysphagia of 11-87%. More than 50% of patients with acute cerebral infarction are associated with different degrees of dysphagia. The incidence of dysphagia in stroke patients is about 51-73%. Patients with PBA have a problem of difficulty swallowing, so capsules are not suitable for PBA patients, and swallowing capsules increases pain for these patients.
CN113209042, CN107072990 and Journal of affinity Disorders (2014), 167, 333-335 disclose dextromethorphan quinidine capsules and ordinary tablets, which cannot meet the medication requirements of dysphagia patients.
Pharm Dev technol. 24(6), 711-719, 2019, disclose that the lubricant sodium stearyl fumarate in dextromethorphan hydrobromide orally disintegrating tablets can play an enhanced taste masking role. Chem. pharm. Bull. 50(12), 1589-1593, 2002, discloses the taste masking effect and possible taste masking mechanism of sucralose, aspartame, sodium chloride, phosphatidic acid and tannic acid on the quinidine optical isomer quinine, indicating that a consistent bitterness assessment can be obtained with human taste using an electronic sensor (electronic tongue). However, neither of the two taste-masking related documents discloses taste masking of dextromethorphan quinidine compositions. In earlier studies, the inventor of the present application found that after adding common flavoring agents with different concentrations to a dextromethorphan quinidine composition, the evaluation results of electronic tongues show that the taste of the composition, such as bitterness and sourness, is not improved basically, so that intensive studies on taste masking of the dextromethorphan quinidine composition are required.
In view of the above, in order to alleviate the pain of patients, it is highly desirable to develop a new dosage form that can satisfy both taste masking and easy swallowing.
Disclosure of Invention
The invention aims to solve the problems in the prior art and provides a dextromethorphan quinidine composition which is easy to swallow and has good mouthfeel and good dissolution, and a preparation method and application thereof.
The purpose of the invention can be realized by the following technical scheme:
the invention provides a dextromethorphan quinidine composition, which comprises dextromethorphan solid dispersion and quinidine solid dispersion.
The dextromethorphan in the dextromethorphan quinidine composition, dextromethorphan solid dispersion and quinidine solid dispersion of the invention refers to dextromethorphan, pharmaceutically acceptable salts thereof or hydrates thereof, including but not limited to hydrobromide, hydrochloride, phosphate, hydroiodide, nitrate, formate, sulfate, acetate, propionate, butyrate, trifluoroacetate, p-toluenesulfonate, lysine salt, N' dibenzylethylenediamine salt, procaine salt, chloroprocaine salt, diethyleneglycol amine salt, ethylenediamine salt, meglumine salt, lithium salt, sodium salt, potassium salt, calcium salt, magnesium salt or hydrates of the above salts, preferably hydrobromide, hydrochloride, phosphate, hydroiodide or hydrates of the above salts, more preferably hydrobromide or hydrobromide hydrates; "quinidine" refers to quinidine, a pharmaceutically acceptable salt thereof, or a hydrate thereof, including, but not limited to, sulfate, polygalacturonate, hydrochloride, hydroiodide, hydrobromide, phosphate, nitrate, oxalate, p-toluenesulfonate, gluconate, lysine, N' -dibenzylethylenediamine, procaine, chloroprocaine, diethyleneglycol amine, ethylenediamine, meglumine, lithium, sodium, potassium, calcium, magnesium, or a hydrate of the foregoing, preferably sulfate, polygalacturonate, hydrochloride, or a hydrate of the foregoing, more preferably sulfate or sulfate hydrate.
Both dextromethorphan and quinidine have poor taste and are easily dissolved, and both dextromethorphan and quinidine have bitter and numb taste. Solid dispersions are commonly used to facilitate drug dissolution, which is detrimental to the taste-masking of dextromethorphan quinidine. The inventor of the application overcomes the technical prejudice and prepares the dextromethorphan quinidine solid dispersion with good taste masking effect. The prepared solid dispersion is convenient to prepare various preparations which are easy to swallow, and solves the problem of dysphagia of patients with nervous system diseases.
In a preferred embodiment, the dextromethorphan solid dispersion comprises dextromethorphan, a pharmaceutically acceptable salt thereof or a hydrate thereof, a polymeric carrier, and a pore-forming agent.
In a preferred embodiment, the quinidine solid dispersion comprises quinidine, a pharmaceutically acceptable salt thereof, or a hydrate thereof, a polymeric carrier, and a porogen.
The inventor of the application reduces the solubility of dextromethorphan quinidine in mouth by adding a polymer carrier, thereby inhibiting the unacceptable taste of dextromethorphan quinidine and playing a taste masking effect. Meanwhile, in order to ensure the drug effect, the requirement of dissolving dextromethorphan quinidine in gastric juice environment needs to be met. However, for dextromethorphan and quinidine, the solubilities of dextromethorphan and quinidine are higher at different pH values, and after various polymer materials are added, the solubilities at different pH values are increased or decreased at the same time, so that the solubility in the mouth is low enough and the dissolution in the gastric juice environment is large enough, which is difficult to realize by only adding the polymer materials, and simultaneously, the requirements of taste masking and dissolution are met, and a controlled-release pore-forming agent is required to be added.
In a preferred embodiment, the polymeric carrier in the composition of the invention is selected from one or more of hypromellose acetate succinate, hypromellose phthalate, eucalypti, docusate sodium or sodium dodecylbenzene sulphate, preferably one or more of hypromellose phthalate, eucalypti or docusate sodium, more preferably one or more of eucalypti L100-55, eucalypti L100 or docusate sodium 85.
The inventor of the application prepares dextromethorphan and quinidine into solid dispersions respectively with different polymer carriers, detects the solubility of dextromethorphan and quinidine in the obtained solid dispersions, and finds that the bitter taste of the dextromethorphan and the quinidine can be effectively inhibited by combining the artificial taste results with the Eudragit L100-55, the Eudragit L100 and the docusate sodium 85, particularly the Eudragit L100-55.
In a preferred embodiment, the mass of the polymeric carrier in the dextromethorphan solid dispersion is 1 time of the mass of dextromethorphan, the pharmaceutically acceptable salt thereof or the hydrate thereof, and the mass of the polymeric carrier in the quinidine solid dispersion is 0.5 to 1 time of the mass of quinidine, the pharmaceutically acceptable salt thereof or the hydrate thereof.
The addition of the high molecular carrier has great influence on the taste correction and dissolution of dextromethorphan and quinidine. The invention inspects the taste-modifying effect on the premise of ensuring the dissolution of dextromethorphan and quinidine. When the mass ratio of the polymeric carrier to the dextromethorphan hydrobromide is 1:1 and the mass ratio of the polymeric carrier to the quinidine sulfate is 0.5:1 to 1:1, the dissolution of both the dextromethorphan solid dispersion and the quinidine solid dispersion can meet the drug dissolution requirement.
In a preferred embodiment, the porogen in the composition of the present invention is selected from one or more of polyvinylpyrrolidone K30, citric acid, hydroxypropyl methylcellulose or polyethylene glycol 8000, preferably one or more of polyvinylpyrrolidone K30 or citric acid, more preferably polyvinylpyrrolidone K30.
After the appropriate high molecular material is added, the bitter taste of the dextromethorphan quinidine composition can be corrected on the premise of ensuring the dissolution of dextromethorphan quinidine in vivo, but the tingling and gritty feelings of the dextromethorphan quinidine composition can not be corrected. The addition of pore-forming agent can mask the tongue and gravel feeling well.
In a preferred embodiment, the mass of the inventive porogen is 0.05-0.2 times, preferably 0.15 times the mass of dextromethorphan, its pharmaceutically acceptable salt or its hydrate or quinidine, its pharmaceutically acceptable salt or its hydrate.
After adding a proper amount of pore-forming agent, the solid dispersion completely meets the requirements of taste correction and preparation dissolution.
In a preferred embodiment, the dextromethorphan quinidine composition provided by the invention can be prepared into an oral preparation, and the oral preparation can be granules, orally disintegrating tablets, solutions, capsules or tablets, and preferably granules, orally disintegrating tablets or solutions.
The dextromethorphan solid dispersion and the quinidine solid dispersion prepared by the invention are mixed with common corresponding auxiliary materials, and a dextromethorphan quinidine oral preparation which is easy to swallow can be simply and conveniently prepared by adopting a conventional preparation process. Such as dextromethorphan quinidine granules, dextromethorphan quinidine orally disintegrating tablets, dextromethorphan quinidine solution and the like.
Another object of the present invention is to provide a dextromethorphan quinidine composition for use in the preparation of a medicament for treating and/or preventing pseudobulbar mood, dysphagia, salivation or speech disorders, cognitive deficits in patients with neurological disorders.
Compared with the prior art, the invention provides a solid-component composition of dextromethorphan quinidine. The composition can realize that dextromethorphan quinidine is basically insoluble in oral cavity but is greatly dissolved out in gastric juice environment, so that the taste which is difficult to accept by dextromethorphan quinidine in the process of taking the composition is avoided, and the requirement of patent medicine is met. The solid components can be easily prepared into preparations such as granules, orally disintegrating tablets or oral liquid and the like which are convenient to swallow, so that the problem of dysphagia of patients with nervous system diseases is solved, and the medication experience of the patients can be greatly improved. In addition, the composition provided by the invention has the advantages of simple preparation process, no need of special production equipment, low cost and suitability for industrial large-scale production.
Detailed Description
The technical solution of the present invention will be further described in detail with reference to the following embodiments. It is to be understood that the following examples are only illustrative and explanatory of the present invention and should not be construed as limiting the scope of the present invention. All the techniques realized based on the above-mentioned contents of the present invention are covered in the protection scope of the present invention.
Unless otherwise specified, the raw materials and reagents used in the following examples are all commercially available products or can be prepared by known methods.
Example 1
Dissolving dextromethorphan hydrobromide, quinidine sulfate and a high molecular carrier in ethanol to prepare a solution of 5mg/mL, sucking 0.2mL of the high molecular carrier solution, adding the solution into a hole of a high-throughput experimental device, sucking 0.1mL of the dextromethorphan hydrobromide solution and 0.1mL of the quinidine sulfate solution respectively, adding the solutions into the hole filled with the high molecular carrier solution, oscillating the solutions on a high-throughput instrument, and drying the hole plate in a vacuum oven to obtain the dextromethorphan hydrobromide solid dispersion containing the high molecular carrier and the quinidine sulfate solid dispersion containing the high molecular carrier respectively.
And adding 0.5mL of water into the prepared solid dispersion, sucking 100 muL of solution at 60s, and diluting after centrifugation to obtain a detection sample. The solubility (μ g/mL) of the sample was measured to obtain the solubility of the solid dispersion containing different polymer carriers for 60s, and the results are shown in Table 1.
The samples were tasted manually as follows: volunteers did not eat, drink, or chew gum for at least 1h prior to testing and rinsed with deionized water. The volunteers retained the sample in their mouths, spit out after 10s, rinse with deionized water until no bad breath in the mouth and taste the next sample. The tasted solid dispersion was evaluated as "bitter, not bitter".
The results show that when the solubility of dextromethorphan is 24.2 mug/mL and the solubility of quinidine is 6.0 mug/mL, the bitter taste of dextromethorphan and quinidine cannot be felt by mouth taste. Therefore, the Eudragit L100-55, the Eudragit L100 and docusate sodium 85 are all polymer materials suitable for dextromethorphan quinidine.
Example 2
Weighing dextromethorphan hydrobromide and quinidine sulfate, respectively adding the obtained mixture into Eudragit L100-55 and an appropriate amount of ethanol, stirring, performing ultrasonic treatment until the mixture is dissolved and clarified, performing spray drying in a spray dryer, collecting a sample into a glass bottle after the spray drying, and drying in a vacuum drying oven to respectively obtain the dextromethorphan hydrobromide solid dispersion and the quinidine sulfate solid dispersion.
Solid dispersions of dextromethorphan or quinidine and Evittx L100-55 in different ratios were prepared according to the above method, and the dissolution of the solid components in a sodium chloride hydrochloride buffer (37 ℃) with pH1.2 in different ratios was examined, and the results are shown in Table 2 below.
The results show that the dissolution of both dextromethorphan and quinidine increases first and then decreases as the ratio of the high molecular material increases. When the mass ratio of the polymeric carrier to the dextromethorphan hydrobromide is 1:1 and the mass ratio of the polymeric carrier to the quinidine sulfate is 0.5: 1-1: 1, the dissolution rates of the dextromethorphan solid dispersion and the quinidine solid dispersion can reach more than 85 percent in 45min, and the dissolution requirements of medicines are met.
Each of the solid dispersions was tasted by the method of artificial taste in example 1. The solid dispersions were evaluated for bitterness, tingling, sourness, dryness, gritty feel, Y for corresponding taste,/for no corresponding taste, and the results are given in table 3 below.
The result shows that for dextromethorphan, when the mass ratio of the polymer carrier to the dextromethorphan is 1:1, good taste-modifying effect can be obtained. However, in the case of quinidine, when the mass ratio of the polymeric carrier to quinidine is 1:1 or 0.5:1, the tingling and gritty feeling of the solid dispersion is not improved, and when the mass ratio is 0.5:1, the bitterness of quinidine is not even improved, so that no satisfactory taste-modifying effect is obtained in the quinidine solid dispersion.
Example 3
Dextromethorphan hydrobromide, quinidine sulfate and Eudragit L100-55 are respectively dissolved in ethanol to respectively prepare 20mg/mL solution, and a pore-forming agent is dissolved in the ethanol to prepare 10mg/mL solution. Respectively adding the same volume of the Eudragit L100-55 solution, the dextromethorphan hydrobromide solution or the quinidine sulfate solution into holes of a high-throughput experimental device, adding different volumes of pore-forming agent solutions, oscillating on a high-throughput instrument, and drying the hole plate in a vacuum oven to respectively obtain dextromethorphan hydrobromide solid dispersoids and quinidine sulfate solid dispersoids with different pore-forming agent contents. Using different porogens, solid dispersions were prepared as shown in table 4 below.
Each of the solid dispersions was tasted by the method of artificial taste in example 1. The solid dispersion was evaluated for bitterness, tingling, sourness, sweetness, dryness, gritty feel. When the pore-forming agents are polyvinylpyrrolidone K30 and citric acid, particularly polyvinylpyrrolidone K30, the solid dispersion prepared under the three different mass ratios has a good taste masking effect.
Example 4
Weighing 500mg of dextromethorphan hydrobromide, 500mg of Eudragit L100-55 and 75mg of polyvinylpyrrolidone K30 into a beaker, adding 50mL of ethanol, stirring, performing ultrasonic treatment to dissolve and clarify, spray-drying in a spray dryer, collecting a sample in a glass bottle, and drying in a vacuum drying oven at 35 ℃ to obtain the dextromethorphan hydrobromide solid dispersion.
Weighing 500mg of quinidine sulfate, 500mg of Eudragit L100-55 and 75mg of polyvinylpyrrolidone K30 into a beaker, adding 50mL of ethanol, stirring, performing ultrasonic treatment to dissolve and clarify, spray-drying in a spray dryer, collecting a sample in a glass bottle, and drying in a vacuum drying oven at 35 ℃ to obtain the dextromethorphan hydrobromide solid dispersion.
And preparing the prepared dextromethorphan hydrobromide solid dispersion, the prepared quinidine sulfate solid dispersion and one or more of a filler, a lubricant and a disintegrant into a dextromethorphan quinidine composition according to a conventional preparation method.
Example 5
The solid dispersion obtained in example 4 was tasted by the artificial taste method of example 1. The solid dispersion was evaluated for bitterness, tingling, sourness, dryness, gritty, Y indicated corresponding taste,/indicated no corresponding taste, and the results are shown in table 5 below.
TABLE 5
| Name (R) | Bitter taste | Tongue with numbness | Sour taste | Hair drier | Sense of gravel |
| Dextromethorphan hydrobromide solid dispersion | / | / | / | / | / |
| Quinidine sulfate solid dispersion | / | / | / | / | / |
The results show that the solid dispersion composition of the invention has no bitter taste, tongue-numbing feeling, sour taste, dryness and gritty feeling in oral cavity, and the solid dispersion of the invention has good taste-modifying effect on dextromethorphan and quinidine.
Example 6
The dissolution of the dextromethorphan hydrobromide solid dispersion and the quinidine sulfate solid dispersion prepared in example 4 in the sodium chloride hydrochloride buffer (37 ℃) with the pH value of 1.2 is tested by a second method according to the dissolution and release test method of the four parts of the Chinese pharmacopoeia 2020 edition, and the results are shown in Table 6.
The result shows that the solid dispersion obtained by the invention has better dissolution rate in gastric juice environment, the dissolution rates of dextromethorphan hydrobromide and quinidine sulfate reach more than 85% in 45min, and the requirement of the quick-release preparation on the dissolution rate is met.
It should be noted that the above-mentioned several preferred embodiments are further non-limiting detailed descriptions of the technical solutions of the present invention, and are only used for illustrating the technical concepts and features of the present invention. It is intended that the present invention be understood and implemented by those skilled in the art, and not limited to the scope of the present invention. All equivalent changes and modifications made according to the spirit of the present invention should be covered within the protection scope of the present invention.
Claims (7)
1. A dextromethorphan quinidine composition, which is characterized in that: comprises dextromethorphan solid dispersion and quinidine solid dispersion, wherein the dextromethorphan solid dispersion comprises dextromethorphan, pharmaceutically acceptable salt or hydrate thereof, a high molecular carrier and a pore-forming agent, and the quinidine solid dispersion comprises quinidine, pharmaceutically acceptable salt or hydrate thereof, a high molecular carrier and a pore-forming agent; the polymer carrier is one or more of Eudragit L100-55, Eudragit L100 or docusate sodium 85; the mass of the macromolecular carrier in the dextromethorphan solid dispersion is 1 time of that of dextromethorphan, pharmaceutically acceptable salt thereof or hydrate thereof, and the mass of the macromolecular carrier in the quinidine solid dispersion is 1 time of that of quinidine, pharmaceutically acceptable salt thereof or hydrate thereof; the pore-foaming agent is one or more of polyvinylpyrrolidone K30 or citric acid.
2. The composition of claim 1, wherein: the pore-foaming agent is polyvinylpyrrolidone K30.
3. The composition of claim 1, wherein: the mass of the pore-forming agent is 0.05 to 0.2 times of that of dextromethorphan, pharmaceutically acceptable salt thereof or hydrate thereof or quinidine, pharmaceutically acceptable salt thereof or hydrate thereof.
4. The composition of claim 3, wherein: the mass of the pore-foaming agent is 0.15 times of that of dextromethorphan, pharmaceutically acceptable salts thereof or hydrates thereof or quinidine, pharmaceutically acceptable salts thereof or hydrates thereof.
5. The composition of claim 1, wherein: the composition can be prepared into oral preparations.
6. The composition of claim 5, wherein: the oral preparation is a granule, an orally disintegrating tablet or a solution.
7. Use of a composition according to claim 1 for the preparation of a medicament for the treatment and/or prevention of pseudobulbar mood, dysphagia, sialorrhea or speech disorders, cognitive deficits in patients with neurological disorders.
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| US20030064108A1 (en) * | 1996-04-23 | 2003-04-03 | Stefan Lukas | Taste masked pharmaceutical compositions |
| US6153220A (en) * | 1997-10-03 | 2000-11-28 | Elan Corporation, Plc | Taste-masked formulations |
| TW200410714A (en) * | 2002-08-07 | 2004-07-01 | Smithkline Beecham Corp | Electrospun amorphous pharmaceutical compositions |
| US20060039981A1 (en) * | 2002-09-04 | 2006-02-23 | Deepak Murpani | Taste masked dosage forms and processes for their preparation |
| US10231929B2 (en) * | 2014-03-18 | 2019-03-19 | Takeda Pharmaceutical Company Limited | Solid dispersion |
| CN103990132B (en) * | 2014-05-07 | 2016-03-30 | 北京化工大学 | A kind of method of acrylic resin mixing water dispersion taste masking preparation |
| CN110548008A (en) * | 2018-06-01 | 2019-12-10 | 广东东阳光药业有限公司 | Acotiamide solid dispersion and composition thereof |
| CN113209042A (en) * | 2021-05-28 | 2021-08-06 | 珠海润都制药股份有限公司 | Dextromethorphan hydrobromide quinidine sulfate capsule and preparation method thereof |
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