CN107441068B - Clonidine hydrochloride oral film and preparation method thereof - Google Patents
Clonidine hydrochloride oral film and preparation method thereof Download PDFInfo
- Publication number
- CN107441068B CN107441068B CN201710736034.0A CN201710736034A CN107441068B CN 107441068 B CN107441068 B CN 107441068B CN 201710736034 A CN201710736034 A CN 201710736034A CN 107441068 B CN107441068 B CN 107441068B
- Authority
- CN
- China
- Prior art keywords
- clonidine hydrochloride
- film
- prescription amount
- glass plate
- cooling
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Classifications
-
- 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
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4168—1,3-Diazoles having a nitrogen attached in position 2, e.g. clonidine
-
- 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
- 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
- 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
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61K47/38—Cellulose; Derivatives thereof
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Inorganic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Nutrition Science (AREA)
- Physiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention belongs to the field of pharmaceutical preparations, and particularly relates to a clonidine hydrochloride oral film and a preparation method thereof. The technical scheme adopted by the invention is that the clonidine hydrochloride oral film agent is characterized by comprising the following components: clonidine hydrochloride, a film forming material, a disintegrating agent, a plasticizer, a flavoring agent and a coloring agent. The clonidine hydrochloride oral film agent prepared by the invention is convenient to take and good in taste, and is beneficial to improving the safety and compliance of patients in taking medicine; the oral cavity is fast dissolved, the bioavailability is high, and the absorption and the curative effect of the medicine are accelerated; has uniform content and good stability. The preparation process of the clonidine hydrochloride oral film agent has simple process, is easy to control, is suitable for industrial production, and obtains unexpected technical effects.
Description
Technical Field
The invention belongs to the field of pharmaceutical preparations, and particularly relates to a clonidine hydrochloride oral film and a preparation method thereof.
Background
Clonidine hydrochloride directly excites the central postsynaptic membrane alpha 2 receptors of the hypothalamus and the brain, which leads to the excitation of inhibitory neurons and reduces the efferent of central sympathetic impulses, thereby inhibiting the activity of peripheral sympathetic nerves. Clonidine hydrochloride tablet, prescription type medicine, orally taken. Is mainly used for treating hypertension, hypertensive emergency, migraine, menopausal hot flashes, dysmenorrhea and withdrawal symptoms of opiate addiction.
Clonidine hydrochloride sustained release tablets were developed by Addrenex Pharmaceuticals, usa, and were approved by FDA in us for the treatment of hypertension on 9/29 th 2009, specification: 0.1mg, 0.2 mg. On 30/9/2009, Shionogi Pharma filed a new drug supplement application for adding clonidine hydrochloride sustained-release tablet indications to the FDA, and on 28/9/2010, the ADHD approved by the U.S. FDA for treating 6-17-year-old children and adolescents was obtained, and the clonidine hydrochloride sustained-release tablet with the specification of 0.1mg was marketed in the U.S. on 2011 1/2011.
Currently, clonidine hydrochloride is marketed in the form of common tablets, sustained release tablets, pellets, microspheres, patches, liposomes, gels, and the like. CN104138362A adopts a solvent dispersion method to dissolve the clonidine hydrochloride raw material medicine into a proper amount of wetting agent, which mainly solves the problem of uneven content in the preparation process of the clonidine hydrochloride sustained release tablets; CN104352473A introduces a preparation method of sustained-release tablets taking hypromellose as a sustained-release framework material; CN102138906A introduces a preparation method of clonidine hydrochloride sustained-release pellets. The clonidine patch can exert its medicinal effect for a long period of 1 week after it is applied to the skin. CN105311002A discloses a method for preparing a clonidine controlled release patch; CN105362255A discloses a clonidine patch and a preparation method thereof. In other aspects, CN104523683A discloses a clonidine hydrochloride dry suspension and a preparation method thereof; CN101536981A discloses clonidine hydrochloride multivesicular liposome and a preparation method thereof; CN101342171A discloses a clonidine hydrochloride in-situ forming eye gel. However, the human body is easy to form thrombus at dawn, so that ischemic cerebral apoplexy is easy to occur, especially for patients with hypertension. Therefore, how to deal with the emergency is the focus of attention of researchers to provide a clonidine hydrochloride preparation which is convenient to take and can be rapidly disintegrated.
The oral membrane agent is used as a new oral drug delivery system, directly acts on oral mucosa tissues, can quickly exert drug effect and keep a certain concentration, has the characteristics of accurate drug content and good stability of tablets, has the advantages of quick absorption and good curative effect of liquid preparations, and has simple preparation process and strong operability. Because of its small volume, it is convenient to transport and carry; also has the advantages of no toxicity, no irritation, definite curative effect, small dosage and the like. The results of bioequivalence tests on healthy adult men as the study object show that the treatment effect of the oral film agent is equivalent to that of the corresponding oral rapidly disintegrating tablet whether the oral film agent is taken with water or not.
Disclosure of Invention
In order to solve the problems, the invention provides a clonidine hydrochloride oral film agent which can be rapidly disintegrated and absorbed, is convenient to take, and has high safety, high compliance and high bioavailability; more specifically, the clonidine hydrochloride oral film provided by the invention can be quickly dissolved in the oral cavity without water and chewing.
In order to achieve the purpose, the invention adopts the technical scheme that:
the clonidine hydrochloride oral film is characterized by comprising the following components: clonidine hydrochloride, a film forming material, a disintegrating agent, a plasticizer, a flavoring agent and a coloring agent.
Further, the clonidine hydrochloride oral film agent contains 2-35 wt% of clonidine hydrochloride, preferably 5-30 wt%, 10-20 wt% and 15 wt%; or preferably 3%, 4%, 6%, 7%, 8%, 9%, 11%, 12%, 13%, 14%, 16%, 17%, 18%, 19%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 31%, 32%, 33%, 34% by weight, etc.
Further, the film forming material is selected from one or a mixture of more than two of poloxamer, hydroxypropyl methylcellulose (HPMC), hydroxypropyl cellulose (HPC), polyvinyl alcohol (PVA), sodium carboxymethylcellulose (CMCNa), Polyoxyethylene (PEO), povidone (PVP), acrylic resin, corn starch, xanthan gum, sodium alginate, gelatin, dextrin, shellac, arabic gum, methylcellulose, agar and sodium alginate. Preferably one or a mixture of more than two of poloxamer, polyvinyl alcohol and sodium alginate. The weight percentage content of the film forming material in the clonidine hydrochloride oral film agent is 2-98%, preferably 5-95%, 10-90%, 20-80%, 30-70%, 40-60% and 50%; and preferably 3%, 4%, 6%, 7%, 8%, 9%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 91%, 92%, 93%, 94%, (wt.), 95%, 96%, 97%, etc.
Further, the disintegrating agent is selected from one or a mixture of more than two of dry starch, sodium carboxymethyl starch and cross-linked PVP, and the sodium carboxymethyl starch is preferred. The weight percentage content of the disintegrant in the clonidine hydrochloride oral film is 0-20%, preferably 10-15%; or preferably 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 11%, 12%, 13%, 14%, 16%, 17%, 18%, 19% by weight.
Further, the plasticizer is selected from one or a mixture of more than two of polyethylene glycol (PEG), glycerol, sorbitol, Tween 80, propylene glycol, ethylene glycol, silicone oil, polypropylene glycol and hexanediol. Polyethylene glycol or glycerol are preferred. The clonidine hydrochloride oral film contains 2-35 wt% of plasticizer, preferably 5-30 wt%, 10-25 wt% and 15-20 wt%, or contains 3 wt%, 4 wt%, 6 wt%, 7 wt%, 8 wt%, 9 wt%, 11 wt%, 12 wt%, 13 wt%, 14 wt%, 16 wt%, 17 wt%, 18 wt%, 19 wt%, 21 wt%, 22 wt%, 23 wt%, 24 wt%, 26 wt%, 27 wt%, 28 wt%, 29 wt%, 31 wt%, 32 wt%, 33 wt% and 34 wt%.
Further, the flavoring agent is selected from one or more of sucralose, aspartame, acesulfame potassium, xylitol, stevioside, glycyrrhizin, saccharin sodium, fructose, sucrose and peppermint essence. The content of the corrigent in the clonidine hydrochloride oral film is 0-25% by weight, preferably 5-20% by weight and 10-15% by weight; or preferably 1%, 2%, 3%, 4%, 6%, 7%, 8%, 9%, 11%, 12%, 13%, 14%, 16%, 17%, 18%, 19%, 21%, 22%, 23%, 24% by weight, etc.
Further, the colorant is selected from carmine, indigo, beet red, gardenia yellow, carotene and titanium dioxide, or a mixture of two or more of them. The clonidine hydrochloride oral film agent contains 0-5 wt% of colorant, and preferably contains 1%, 2%, 3%, 4% and the like.
Further, the clonidine hydrochloride oral film agent comprises the following components in percentage by weight:
5 to 20 percent of clonidine hydrochloride
40-75% of film forming material
0 to 10 percent of disintegrating agent
5 to 25 percent of plasticizer
0 to 10 percent of flavoring agent
0-5% of a coloring agent.
Further, the clonidine hydrochloride oral film agent comprises the following components in percentage by weight:
10-15% of clonidine hydrochloride
55 to 60 percent of film forming material
2 to 6 percent of disintegrating agent
10-15% of plasticizer
3-8% of flavoring agent
1-3% of a coloring agent.
The invention further provides a preparation method of the clonidine hydrochloride oral film, which is characterized by comprising the following steps:
(1) weighing the film forming material according to the prescription amount, adding water at 40-80 ℃ for swelling, and cooling to 30-60 ℃ when the solution is completely clear;
(2) adding the disintegrant, the plasticizer, the flavoring agent and the coloring agent according to the prescription amount, continuously stirring until the mixture is uniformly mixed, and cooling to the room temperature;
(3) adding clonidine hydrochloride in a prescription amount, fully stirring to dissolve, and uniformly mixing;
(4) standing for 2-4 hours, ultrasonically degassing, and controlling the temperature to be 20-30 ℃ to prepare a membrane material;
(5) and pouring the film material onto the lower edge of the glass plate, pushing the film material forwards by using a push rod to perform film coating, drying, demolding, cutting into required specifications, sealing, packaging and sterilizing to obtain the glass plate.
Further, the water temperature during swelling is preferably 50-70 ℃, and more preferably 60 ℃.
Further, the ultrasound is preferably performed for 10s at a time and 3s at intervals.
Furthermore, the clonidine hydrochloride oral film has good toughness; the melting time is 5 to 40 seconds, preferably 10 to 30 seconds, and more preferably 12 to 20 seconds.
Further, the thickness of the clonidine hydrochloride oral film agent is 50-200 μm, preferably 70-150 μm, and more preferably 90-120 μm.
The clonidine hydrochloride oral film agent prepared by the invention is convenient to take and good in taste, and is beneficial to improving the safety and compliance of patients in taking medicine; the oral cavity is fast dissolved, the bioavailability is high, and the absorption and the curative effect of the medicine are accelerated; has uniform content and good stability. The preparation process of the clonidine hydrochloride oral film agent has simple process, is easy to control, is suitable for industrial production, and obtains unexpected technical effects.
Detailed Description
For a detailed description of the present invention, reference will now be made to specific examples. These examples are illustrative only and do not limit the scope of the present invention in any way. It will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the spirit and scope of the invention, and that such changes and modifications may be made without departing from the spirit and scope of the invention.
Example 1
The clonidine hydrochloride oral film comprises the following components:
clonidine hydrochloride 20g
70g of poloxamer
10g of polyethylene glycol.
The preparation method comprises the following steps:
(1) weighing poloxamer according to the prescription amount, adding 60 ℃ water for swelling, and cooling to 50 ℃ when the solution is completely clear;
(2) adding polyethylene glycol according to the prescription amount, continuously stirring until the mixture is uniformly mixed, and cooling to room temperature;
(3) adding clonidine hydrochloride in a prescription amount, fully stirring to dissolve, and uniformly mixing;
(4) standing for 2 hours, ultrasonically degassing for 10s every time at intervals of 3s, and controlling the temperature to be kept at 20-30 ℃ to prepare a membrane material;
(5) and pouring the film material onto the lower edge of the glass plate, pushing the film material forwards by using a push rod to perform film coating, drying, demolding, cutting into required specifications, sealing, packaging and sterilizing to obtain the glass plate.
Evaluation results were as follows: the clonidine hydrochloride oral film has uniform content and good taste; the material has good toughness, and the melting time is 15 s; the thickness of the film agent was 160. mu.m.
Example 2
The clonidine hydrochloride oral film comprises the following components:
clonidine hydrochloride 10g
Polyvinyl alcohol 80g
Sodium carboxymethyl starch 5g
5g of glycerol.
The preparation method comprises the following steps:
(1) weighing polyvinyl alcohol according to the prescription amount, adding water at 70 ℃ for swelling, and cooling to 50 ℃ when the solution is completely clear;
(2) adding the sodium carboxymethyl starch and the glycerol in the formula amount, continuously stirring until the mixture is uniformly mixed, and cooling to room temperature;
(3) adding clonidine hydrochloride in a prescription amount, fully stirring to dissolve, and uniformly mixing;
(4) standing for 4 hours, ultrasonically degassing for 10s every time at intervals of 3s, and controlling the temperature to be kept at 20-30 ℃ to prepare a membrane material;
(5) and pouring the film material onto the lower edge of the glass plate, pushing the film material forwards by using a push rod to perform film coating, drying, demolding, cutting into required specifications, sealing, packaging and sterilizing to obtain the glass plate.
Evaluation results were as follows: the clonidine hydrochloride oral film has uniform content and good taste; the material has good toughness, and the melting time is 10 s; the thickness of the film agent is 120 μm.
Example 3
The clonidine hydrochloride oral film comprises the following components:
clonidine hydrochloride 15g
Sodium alginate 60g
Crosslinked PVP 5g
Polypropylene glycol 10g
Sucralose 8g
Indigo blue 2 g.
The preparation method comprises the following steps:
(1) weighing sodium alginate according to the prescription amount, adding 50 ℃ water to swell, and cooling to 30 ℃ when the solution is completely clear;
(2) adding cross-linked PVP, polypropylene glycol, sucralose and indigo in the formula amount, continuously stirring until the mixture is uniformly mixed, and cooling to room temperature;
(3) adding clonidine hydrochloride in a prescription amount, fully stirring to dissolve, and uniformly mixing;
(4) standing for 3 hours, ultrasonically degassing for 10s every time at intervals of 3s, and controlling the temperature to be kept at 20-30 ℃ to prepare a membrane material;
(5) and pouring the film material onto the lower edge of the glass plate, pushing the film material forwards by using a push rod to perform film coating, drying, demolding, cutting into required specifications, sealing, packaging and sterilizing to obtain the glass plate.
Evaluation results were as follows: the clonidine hydrochloride oral film has uniform content and sweet taste; the material has good toughness, and the melting time is 8 s; the thickness of the film agent is 80 μm.
Example 4
The clonidine hydrochloride oral film comprises the following components:
clonidine hydrochloride 12g
Hydroxypropyl methylcellulose 68g
Dried starch 4g
Sorbitol 12g
Xylitol 3g
1g of gardenia yellow.
The preparation method comprises the following steps:
(1) weighing hydroxypropyl methylcellulose with the formula amount, adding water at 45 ℃ for swelling, and cooling to 35 ℃ when the solution is completely clear;
(2) adding the dry starch, sorbitol, xylitol and gardenia yellow according to the prescription amount, continuously stirring until the mixture is uniformly mixed, and cooling to room temperature;
(3) adding clonidine hydrochloride in a prescription amount, fully stirring to dissolve, and uniformly mixing;
(4) standing for 2 hours, ultrasonically degassing for 10s every time at intervals of 3s, and controlling the temperature to be kept at 20-30 ℃ to prepare a membrane material;
(5) and pouring the film material onto the lower edge of the glass plate, pushing the film material forwards by using a push rod to perform film coating, drying, demolding, cutting into required specifications, sealing, packaging and sterilizing to obtain the glass plate.
Evaluation results were as follows: the clonidine hydrochloride oral film has uniform content and good taste; has good toughness, and the melting time limit is 22 s; the thickness of the film agent is 140 μm.
Example 5
The clonidine hydrochloride oral film comprises the following components:
clonidine hydrochloride 8g
Povidone 74g
Sodium carboxymethyl starch 10g
Polyethylene glycol 5g
Aspartame 1g
2g of titanium dioxide.
The preparation method comprises the following steps:
(1) weighing povidone with the prescription amount, adding 60 ℃ for swelling, and cooling to 40 ℃ when the solution is completely clear;
(2) adding the sodium carboxymethyl starch, the polyethylene glycol, the aspartame and the titanium dioxide according to the prescription amount, continuously stirring to be uniformly mixed, and cooling to room temperature;
(3) adding clonidine hydrochloride in a prescription amount, fully stirring to dissolve, and uniformly mixing;
(4) standing for 3 hours, ultrasonically degassing for 10s every time at intervals of 3s, and controlling the temperature to be kept at 20-30 ℃ to prepare a membrane material;
(5) and pouring the film material onto the lower edge of the glass plate, pushing the film material forwards by using a push rod to perform film coating, drying, demolding, cutting into required specifications, sealing, packaging and sterilizing to obtain the glass plate.
Evaluation results were as follows: the clonidine hydrochloride oral film has uniform content and sweet taste; the material has good toughness, and the melting time is 6 s; the thickness of the film agent is 60 μm.
Example 6
The clonidine hydrochloride oral film comprises the following components:
clonidine hydrochloride 15g
Poloxamer 40g
Polyvinyl alcohol 20g
Sodium carboxymethyl starch 5g
Polyethylene glycol 13g
Mint essence 4g
Carotene 3g
The preparation method comprises the following steps:
(1) weighing poloxamer and polyvinyl alcohol according to the prescription amount, adding 65 ℃ water for swelling, and cooling to 50 ℃ when the solution is completely clear;
(2) adding the sodium carboxymethyl starch, the polyethylene glycol, the mint essence and the carotene according to the prescription amount, continuously stirring until the mixture is uniformly mixed, and cooling to room temperature;
(3) adding clonidine hydrochloride in a prescription amount, fully stirring to dissolve, and uniformly mixing;
(4) standing for 3 hours, ultrasonically degassing for 10s every time at intervals of 3s, and controlling the temperature to be kept at 20-30 ℃ to prepare a membrane material;
(5) and pouring the film material onto the lower edge of the glass plate, pushing the film material forwards by using a push rod to perform film coating, drying, demolding, cutting into required specifications, sealing, packaging and sterilizing to obtain the glass plate.
Evaluation results were as follows: the clonidine hydrochloride oral film has uniform content and good taste; the product has good toughness, and the melting time is 14 s; the thickness of the film agent is 110 μm.
The foregoing is merely a preferred embodiment of the invention and is not intended to limit the scope of the invention, which is defined by the claims appended hereto, and any other technical entity or method that is encompassed by the claims as broadly defined herein, or equivalent variations thereof, is contemplated as being encompassed by the claims.
Claims (6)
1. The clonidine hydrochloride oral film is characterized by comprising the following components:
clonidine hydrochloride 20g
70g of poloxamer
10g of polyethylene glycol; the preparation method comprises the following steps:
(1) weighing poloxamer according to the prescription amount, adding 60 ℃ water for swelling, and cooling to 50 ℃ when the solution is completely clear;
(2) adding polyethylene glycol according to the prescription amount, continuously stirring until the mixture is uniformly mixed, and cooling to room temperature;
(3) adding clonidine hydrochloride in a prescription amount, fully stirring to dissolve, and uniformly mixing;
(4) standing for 2 hours, ultrasonically degassing for 10s every time at intervals of 3s, and controlling the temperature to be kept at 20-30 ℃ to prepare a membrane material;
(5) and pouring the film material onto the lower edge of the glass plate, pushing the film material forwards by using a push rod to perform film coating, drying, demolding, cutting into required specifications, sealing, packaging and sterilizing to obtain the glass plate.
2. The clonidine hydrochloride oral film is characterized by comprising the following components:
clonidine hydrochloride 10g
Polyvinyl alcohol 80g
Sodium carboxymethyl starch 5g
5g of glycerol; the preparation method comprises the following steps:
(1) weighing polyvinyl alcohol according to the prescription amount, adding water at 70 ℃ for swelling, and cooling to 50 ℃ when the solution is completely clear;
(2) adding the sodium carboxymethyl starch and the glycerol in the formula amount, continuously stirring until the mixture is uniformly mixed, and cooling to room temperature;
(3) adding clonidine hydrochloride in a prescription amount, fully stirring to dissolve, and uniformly mixing;
(4) standing for 4 hours, ultrasonically degassing for 10s every time at intervals of 3s, and controlling the temperature to be kept at 20-30 ℃ to prepare a membrane material;
(5) and pouring the film material onto the lower edge of the glass plate, pushing the film material forwards by using a push rod to perform film coating, drying, demolding, cutting into required specifications, sealing, packaging and sterilizing to obtain the glass plate.
3. The clonidine hydrochloride oral film is characterized by comprising the following components:
clonidine hydrochloride 15g
Sodium alginate 60g
Crosslinked PVP 5g
Polypropylene glycol 10g
Sucralose 8g
2g of indigo; the preparation method comprises the following steps:
(1) weighing sodium alginate according to the prescription amount, adding 50 ℃ water to swell, and cooling to 30 ℃ when the solution is completely clear;
(2) adding cross-linked PVP, polypropylene glycol, sucralose and indigo in the formula amount, continuously stirring until the mixture is uniformly mixed, and cooling to room temperature;
(3) adding clonidine hydrochloride in a prescription amount, fully stirring to dissolve, and uniformly mixing;
(4) standing for 3 hours, ultrasonically degassing for 10s every time at intervals of 3s, and controlling the temperature to be kept at 20-30 ℃ to prepare a membrane material;
(5) and pouring the film material onto the lower edge of the glass plate, pushing the film material forwards by using a push rod to perform film coating, drying, demolding, cutting into required specifications, sealing, packaging and sterilizing to obtain the glass plate.
4. The clonidine hydrochloride oral film is characterized by comprising the following components:
clonidine hydrochloride 12g
Hydroxypropyl methylcellulose 68g
Dried starch 4g
Sorbitol 12g
Xylitol 3g
1g of gardenia yellow; the preparation method comprises the following steps:
(1) weighing hydroxypropyl methylcellulose with the formula amount, adding water at 45 ℃ for swelling, and cooling to 35 ℃ when the solution is completely clear;
(2) adding the dry starch, sorbitol, xylitol and gardenia yellow according to the prescription amount, continuously stirring until the mixture is uniformly mixed, and cooling to room temperature;
(3) adding clonidine hydrochloride in a prescription amount, fully stirring to dissolve, and uniformly mixing;
(4) standing for 2 hours, ultrasonically degassing for 10s every time at intervals of 3s, and controlling the temperature to be kept at 20-30 ℃ to prepare a membrane material;
(5) and pouring the film material onto the lower edge of the glass plate, pushing the film material forwards by using a push rod to perform film coating, drying, demolding, cutting into required specifications, sealing, packaging and sterilizing to obtain the glass plate.
5. The clonidine hydrochloride oral film is characterized by comprising the following components:
clonidine hydrochloride 8g
Povidone 74g
Sodium carboxymethyl starch 10g
Polyethylene glycol 5g
Aspartame 1g
2g of titanium dioxide; the preparation method comprises the following steps:
(1) weighing povidone with the prescription amount, adding 60 ℃ for swelling, and cooling to 40 ℃ when the solution is completely clear;
(2) adding the sodium carboxymethyl starch, the polyethylene glycol, the aspartame and the titanium dioxide according to the prescription amount, continuously stirring to be uniformly mixed, and cooling to room temperature;
(3) adding clonidine hydrochloride in a prescription amount, fully stirring to dissolve, and uniformly mixing;
(4) standing for 3 hours, ultrasonically degassing for 10s every time at intervals of 3s, and controlling the temperature to be kept at 20-30 ℃ to prepare a membrane material;
(5) and pouring the film material onto the lower edge of the glass plate, pushing the film material forwards by using a push rod to perform film coating, drying, demolding, cutting into required specifications, sealing, packaging and sterilizing to obtain the glass plate.
6. The clonidine hydrochloride oral film is characterized by comprising the following components:
clonidine hydrochloride 15g
Poloxamer 40g
Polyvinyl alcohol 20g
Sodium carboxymethyl starch 5g
Polyethylene glycol 13g
Mint essence 4g
3g of carotene; the preparation method comprises the following steps:
(1) weighing poloxamer and polyvinyl alcohol according to the prescription amount, adding 65 ℃ water for swelling, and cooling to 50 ℃ when the solution is completely clear;
(2) adding the sodium carboxymethyl starch, the polyethylene glycol, the mint essence and the carotene according to the prescription amount, continuously stirring until the mixture is uniformly mixed, and cooling to room temperature;
(3) adding clonidine hydrochloride in a prescription amount, fully stirring to dissolve, and uniformly mixing;
(4) standing for 3 hours, ultrasonically degassing for 10s every time at intervals of 3s, and controlling the temperature to be kept at 20-30 ℃ to prepare a membrane material;
(5) and pouring the film material onto the lower edge of the glass plate, pushing the film material forwards by using a push rod to perform film coating, drying, demolding, cutting into required specifications, sealing, packaging and sterilizing to obtain the glass plate.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710736034.0A CN107441068B (en) | 2017-08-24 | 2017-08-24 | Clonidine hydrochloride oral film and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710736034.0A CN107441068B (en) | 2017-08-24 | 2017-08-24 | Clonidine hydrochloride oral film and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN107441068A CN107441068A (en) | 2017-12-08 |
| CN107441068B true CN107441068B (en) | 2021-02-26 |
Family
ID=60493152
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710736034.0A Active CN107441068B (en) | 2017-08-24 | 2017-08-24 | Clonidine hydrochloride oral film and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN107441068B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2618810A (en) * | 2022-05-17 | 2023-11-22 | Novumgen Ltd | Pharmaceutical composition for sublingual administration of clonidine |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| CN115813886B (en) * | 2021-09-18 | 2024-05-10 | 中国药科大学 | Toovilin citrate oral film and preparation method thereof |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101384249A (en) * | 2006-02-17 | 2009-03-11 | 诺瓦提斯公司 | Disintegrable oral films |
| CN102940617A (en) * | 2012-11-21 | 2013-02-27 | 北京润德康医药技术有限公司 | Desloratadine oral dispersible film |
| CN103211801A (en) * | 2013-04-02 | 2013-07-24 | 苏州人本药业有限公司 | Film agent quickly dissolved in oral cavity and preparation method thereof |
| CN105997949A (en) * | 2016-06-02 | 2016-10-12 | 云南省药物研究所 | Oral dissolving film preparation containing bulleyaconitine A and preparation technology of oral dissolving film preparation |
| CN106176690A (en) * | 2016-08-30 | 2016-12-07 | 华熙福瑞达生物医药有限公司 | Hyaluronic acid mouth care film and preparation method and application |
| CN106619577A (en) * | 2016-10-08 | 2017-05-10 | 中国药科大学 | Novel loratadine oral quickly soluble film and preparation method thereof |
-
2017
- 2017-08-24 CN CN201710736034.0A patent/CN107441068B/en active Active
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101384249A (en) * | 2006-02-17 | 2009-03-11 | 诺瓦提斯公司 | Disintegrable oral films |
| CN102940617A (en) * | 2012-11-21 | 2013-02-27 | 北京润德康医药技术有限公司 | Desloratadine oral dispersible film |
| CN103211801A (en) * | 2013-04-02 | 2013-07-24 | 苏州人本药业有限公司 | Film agent quickly dissolved in oral cavity and preparation method thereof |
| CN105997949A (en) * | 2016-06-02 | 2016-10-12 | 云南省药物研究所 | Oral dissolving film preparation containing bulleyaconitine A and preparation technology of oral dissolving film preparation |
| CN106176690A (en) * | 2016-08-30 | 2016-12-07 | 华熙福瑞达生物医药有限公司 | Hyaluronic acid mouth care film and preparation method and application |
| CN106619577A (en) * | 2016-10-08 | 2017-05-10 | 中国药科大学 | Novel loratadine oral quickly soluble film and preparation method thereof |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2618810A (en) * | 2022-05-17 | 2023-11-22 | Novumgen Ltd | Pharmaceutical composition for sublingual administration of clonidine |
Also Published As
| Publication number | Publication date |
|---|---|
| CN107441068A (en) | 2017-12-08 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2426263C (en) | Nateglinide-containing preparation | |
| EP2979707B1 (en) | Composite structural material and pharmaceutical composition thereof | |
| RU2201754C2 (en) | Pharmaceutical composition, method for its obtaining, method for treating psychotic states and hyperactivity | |
| CN107441068B (en) | Clonidine hydrochloride oral film and preparation method thereof | |
| KR20110020782A (en) | Oral contraceptive dosage forms comprising a progestogen dispersed in an enteric polymer and further comprising an estrogen | |
| JPH10194969A (en) | Tablet composition | |
| JP2002526437A (en) | AGITATION-INDEPENDENT PHARMACEUTICAL MULTI-UNIT RELEASE FORMULATION AND PROCESS FOR PRODUCING THE SAME | |
| CN104784157B (en) | A kind of montelukast oral membrane agent of stabilization | |
| CN116211835A (en) | Agomelatine oral film and preparation method thereof | |
| CN109431966A (en) | Edaravone pharmaceutical composition | |
| CN102008469B (en) | Method for preparing telmisartan amlodipine tablets | |
| CN105012276A (en) | Imidafenacin oral fast dissolving film and preparation method and application thereof | |
| CA2378379C (en) | Fast-release extrudates and process for their production, and preparations obtainable therefrom | |
| CN113181143B (en) | 2-oxo-1-pyrrolidine derivative oral dissolving film and preparation method and application thereof | |
| US20170319518A1 (en) | Sodium Ibuprofen Tablets and Methods of Manufacturing Pharmaceutical Compositions Including Sodium Ibuprofen | |
| JP4165224B2 (en) | Effervescent composition | |
| CN116685317A (en) | Solid preparation | |
| CN102442942A (en) | Polymorphic substances of 4-aminopyridine, and preparation and application thereof | |
| CN108938580B (en) | Paroxetine hydrochloride oral disintegrating tablet | |
| CN105596306B (en) | Sodium houttuyfonate tablet composite and preparation method thereof | |
| CN109010323A (en) | Molten film of rivastigmine-hydrogentartrate mouth and preparation method thereof | |
| CN100450548C (en) | Oral patches containing pdacrilin resin composition and its preparing method | |
| CN110840863B (en) | Oral quick-dissolving film agent of alexanide and preparation method thereof | |
| CN113952312A (en) | Silodosin medicine absorbed through oral mucosa | |
| CN113712928A (en) | Brivudine drug absorbed through oral mucosa |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| CB02 | Change of applicant information |
Address after: 266103 block L, Haier Industrial Park, Laoshan District, Qingdao City, Shandong Province Applicant after: CP PHARMACEUTICAL (QINGDAO) Co.,Ltd. Address before: 266103 block L, Haier Industrial Park, Laoshan District, Qingdao City, Shandong Province Applicant before: Qingdao Zhengda Haier Pharmaceutical Co.,Ltd. Address after: No.3601 Tuanjie Road, Qingdao Economic and Technological Development Zone, Shandong Province 266426 Applicant after: CP PHARMACEUTICAL (QINGDAO) Co.,Ltd. Address before: 266103 block L, Haier Industrial Park, Laoshan District, Qingdao City, Shandong Province Applicant before: CP PHARMACEUTICAL (QINGDAO) Co.,Ltd. |
|
| CB02 | Change of applicant information | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |