CN116115584A - Dextromethorphan sustained-release pellets and suspension - Google Patents
Dextromethorphan sustained-release pellets and suspension Download PDFInfo
- Publication number
- CN116115584A CN116115584A CN202211705125.5A CN202211705125A CN116115584A CN 116115584 A CN116115584 A CN 116115584A CN 202211705125 A CN202211705125 A CN 202211705125A CN 116115584 A CN116115584 A CN 116115584A
- Authority
- CN
- China
- Prior art keywords
- dextromethorphan
- drug
- parts
- release
- pellet
- 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.)
- Pending
Links
Images
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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/5021—Organic macromolecular compounds
- A61K9/5036—Polysaccharides, e.g. gums, alginate; Cyclodextrin
- A61K9/5042—Cellulose; Cellulose derivatives, e.g. phthalate or acetate succinate esters of hydroxypropyl methylcellulose
- A61K9/5047—Cellulose ethers containing no ester groups, e.g. hydroxypropyl methylcellulose
-
- 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
-
- 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
-
- 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
- A61K9/10—Dispersions; Emulsions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/5021—Organic macromolecular compounds
- A61K9/5026—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/14—Antitussive agents
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pulmonology (AREA)
- Dispersion Chemistry (AREA)
- Inorganic Chemistry (AREA)
- Emergency Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a dextromethorphan sustained-release pellet and suspension, and the preparation method comprises the following steps: s1, taking dextromethorphan hydrobromide as a raw material drug and taking a microcrystalline cellulose pellet core as a drug carrying material, and obtaining a drug-containing pellet with the drug contained in the interior and the surface by adopting an adsorption drying method; s2, coating the drug-containing pellets by using a slightly soluble, insoluble or water-insoluble material in water as a slow-release coating material and using a water-soluble material as a plasticizer to obtain the dextromethorphan slow-release pellets. The dextromethorphan oral preparation can slowly release active substances in a human body, continuously exert the drug effect and improve the compliance of patients.
Description
Technical Field
The invention belongs to the field of sustained release preparations, and particularly relates to dextromethorphan sustained release pellets and suspension.
Background
Cough is a main symptom of respiratory diseases, a protective reflex, and has the effects of promoting sputum and foreign matters in respiratory tract to be discharged and keeping respiratory tract clean and unobstructed. Slight cough can help to clear phlegm and foreign matters in the trachea, can be naturally relieved, and generally does not need to take cough-relieving medicines; intense and frequent coughs, especially dry cough, can affect rest and sleep, even aggravate illness and cause other complications, and cough relieving and phlegm reducing medicines are needed to be added while aiming at etiology treatment.
Dextromethorphan is the dextroisomer of morphine levorphanol methyl ether, and plays a central antitussive role by inhibiting the medullary cough center, and the antitussive strength is equal to or slightly stronger than codeine; has no analgesic effect, and tolerance and addiction are not seen in long-term application. Therapeutic doses do not inhibit respiration. The oral administration is good, the effect is achieved within 15-30 minutes, the effect can be maintained for 3-6 hours, and the concentration of the proto-drug in the blood plasma is very low.
Common dextromethorphan formulations are often administered several times a day, e.g., 3-4 times a day for common tablets, 1-2 tablets (15 mg/tablet) each time. Patients can intentionally and unintentionally change the drug taking scheme due to fear of trouble and the like, the drug level concentration in blood plasma and tissues fluctuates greatly due to the fact that the patients take the drug once or twice, even if the drug is continuously taken, the treatment concentration can not be reached in a short period, the treatment level can be rebuilt only by repeated administration, and the drug is wasted and the treatment is delayed. Therefore, the development of a sustained release preparation of dextromethorphan meets the prospect and the demand of clinical application.
Disclosure of Invention
Based on the technical problems, the invention provides the dextromethorphan sustained-release pellets and the suspension, wherein the dextromethorphan sustained-release preparation has higher drug loading rate, can slowly release drugs in a human body, continuously plays the drug effect, and improves the compliance of patients.
The specific scheme of the invention is as follows:
the invention aims at providing a dextromethorphan sustained-release pellet, and the preparation method comprises the following steps: s1, taking dextromethorphan hydrobromide as a raw material drug and taking a microcrystalline cellulose pellet core as a drug carrying material, and obtaining a drug-containing pellet with the drug contained in the interior and the surface by adopting an adsorption drying method; s2, coating the drug-containing pellets by using a slightly soluble, insoluble or water-insoluble material in water as a slow-release coating material and using a water-soluble material as a plasticizer to obtain the dextromethorphan slow-release pellets.
The microcrystalline cellulose pellet core is specifically selected as a drug-carrying material, and firstly, the special microscopic characteristics determine that the microcrystalline cellulose pellet core is easy to form a porous structure, so that an advantage condition is provided for improving the drug-carrying quantity; secondly, in the adsorption process, the excellent structural rigidity ensures the stability of the structure after adsorption, and is beneficial to the subsequent coating; finally, microcrystalline cellulose is insoluble in water but has a certain hydrophilicity, and water can smoothly enter the pill core, so that the medicine in the microcrystalline cellulose is released. Further, when preparing the drug-containing pellets, an adsorption drying method is selected to obtain the drug-containing pellets with drugs both inside and on the surface, and compared with the existing coating method, the drug-loading rate is improved to a great extent by obtaining the pellets with drugs only on the surface; and the active ingredients are adsorbed in the medicine-carrying material, so that the slow release of the medicine is facilitated. Furthermore, the plasticizer with better water solubility is selected to be matched with the coating material which is slightly soluble/insoluble in water during coating, so as to improve the film forming property of the coating film and regulate the drug release rate.
Compared with the existing dextromethorphan pellets adopting cationic resin as a drug-carrying material, the invention uses microcrystalline cellulose pellet cores to be matched with specific coating materials and auxiliary materials, thereby ensuring high drug-carrying capacity and prolonging the release of drugs.
Preferably, the weight ratio of the microcrystalline cellulose pellet core to the dextromethorphan hydrobromide bulk drug is 1-2:2.
Preferably, the microcrystalline cellulose micropellet core D90 has a particle size of 100-200 μm.
The invention controls the D90 particle size of the microcrystalline cellulose pellet core to be 100-200 mu m, has larger specific surface area and stronger adsorption capacity, and under the condition of the particle size, the water absorption rate of the microcrystalline cellulose pellet core can reach 100-130%, and is favorable for preparing dextromethorphan slow-release suspension in later stage.
Preferably, the microcrystalline cellulose micropellet core is selected from commercially available finished products or is self-made; more preferably, the microcrystalline cellulose pellet core preparation method comprises the following steps: adding microcrystalline cellulose into water, and homogenizing to obtain an aqueous microcrystalline cellulose filter cake; and drying the microcrystalline cellulose filter cake, and adopting an extrusion spheronization method.
The core of the commercially available microcrystalline cellulose pellets is not particularly limited, and includes, but is not limited to: the current commercial Asahi chemical industry
Dongchen pharmaceutical->
Etc.
Preferably, the moisture of the drug-containing pellets is less than or equal to 3%; the weight of the drug-containing micropellets is increased by 55-65% relative to the microcrystalline cellulose micropellet core.
Preferably, the adsorption drying method specifically includes: dissolving dextromethorphan hydrobromide bulk drug in a solvent to obtain a drug-containing solution; placing microcrystalline cellulose pellet core into the drug-containing solution, stirring for 4-6h, filtering and drying to obtain drug-containing pellet; more preferably, the solvent is 50-80% ethanol; more preferably, the concentration of the medicated solution is 10-50%; more preferably, the stirring rate is 10-20rpm.
When the drug-containing pellets are prepared, the proper solvent is selected to dissolve the raw materials, so that the raw materials can be well dissolved, the subsequent drying is convenient, and the solvent is better removed; meanwhile, the solvent cannot damage the structure of the microcrystalline cellulose pellet core, so that the integrity and rigidity of the pellet core can be maintained after the raw material medicine is adsorbed.
When the drug-containing pellets are prepared, ethanol is preferably used as a solvent, dextromethorphan hydrobromide serving as a raw material drug is easily dissolved in an ethanol solution, but microcrystalline cellulose pellet cores are insoluble in the ethanol solution, so that the pellet cores can still keep a spherical structure after the raw material drug solution is fully adsorbed, and the solvent is more easily volatilized and removed in the drying process; in the process, the pellet cores are only slightly swelled due to absorption, and immediately recover after drying, so that the friability is not affected, and the integrity and rigidity of the pellet cores can be well maintained.
The micropill pill core is placed in the high-concentration drug-containing solution, and the drug-containing solution is contacted with the micropill pill core through stirring at a low speed for a long time, so that the microcrystalline cellulose micropill pill core is ensured to fully adsorb the raw materials.
The method of drying is not particularly limited, and a conventional drying method may be employed; such as, but not limited to, heated air circulation oven drying, fluid bed drying, and the like; preferably, fluidized bed drying is employed, so that drying efficiency and uniformity can be improved.
Preferably, the slow release coating material is selected from one or more of celluloses, polyacrylic resins and derivatives thereof, polydimethylsiloxanes and analogues thereof; more preferably, the cellulose-based coating material is cellulose acetate or ethylcellulose.
Preferably, the plasticizer is selected from one or more of polyethylene glycol, triethyl citrate, diethyl phthalate; more preferably, the coating is weighted 5-8%.
The second object of the invention is to provide dextromethorphan suspension, which comprises dextromethorphan sustained-release pellets according to any one of the above.
Preferably, the dextromethorphan suspension comprises, by weight: 200-300 parts of dextromethorphan sustained-release pellets, 20-30 parts of thickening agent, 6-10 parts of pH regulator, 5-10 parts of corrigent, 1-5 parts of bacteriostat and 200-300 parts of water; more preferably, the food additive also comprises 1-2 parts of food essence and 1-5 parts of food pigment.
In the suspension, the thickener, pH regulator, correctant, bacteriostat, edible essence and edible pigment are not particularly limited. Such as thickeners include, but are not limited to, sodium carboxymethyl cellulose, hypromellose, xanthan gum, acacia, and the like; pH modifiers include, but are not limited to, citric acid, lactic acid, tartaric acid, and the like; flavoring agents include, but are not limited to, sucrose, sodium saccharin, sucralose, aspartame, etc.; bacteriostats include, but are not limited to, sodium benzoate, methylparaben, ethylparaben, and the like; the edible pigment and the corresponding edible essence are matched and selected, including but not limited to, yellow pigment and lemon essence or pineapple essence are matched; the red pigment is matched with watermelon essence or strawberry essence.
The method for preparing the suspension is not particularly limited, and conventional methods may be employed. If the rest auxiliary materials of the suspension are dissolved into the solvent in the stirring process, then the prepared dextromethorphan slow-release pellets are put into the solvent, finally the mixture is uniformly filled into HDPE bottles or glass bottles with proper sizes through a filling machine, and the finished product is obtained after capping.
The invention has the beneficial effects that:
the invention provides a dextromethorphan sustained-release pellet and a suspension, wherein the dextromethorphan sustained-release preparation has a simple preparation process, can reduce burst release while improving the drug loading rate, ensures that the drug can be stably released in the drug application period, prolongs the action time of the drug, reduces the administration times of patients and improves the compliance of the patients.
Drawings
FIG. 1 is a flow chart of a preparation process of the drug-containing pellets of the invention;
FIG. 2 is a flow chart of a preparation process of the sustained-release pellets of the invention;
FIG. 3 is a flow chart of a process for preparing a suspension of the present invention;
FIG. 4 is an in vitro release profile of dextromethorphan suspensions prepared in examples 2 and 3;
Detailed Description
The technical scheme of the present invention will be described in detail by means of specific examples, which should be explicitly set forth for illustration, but should not be construed as limiting the scope of the present invention.
Example 1
The dextromethorphan sustained-release pellet is prepared by the following steps:
s1, preparing a drug-containing pellet: 200 parts of dextromethorphan hydrobromide raw material medicine is taken and added into 300 parts of 50% ethanol solution, and stirred for 30 minutes at 300rpm to obtain medicine-containing solution; then 150 parts of microcrystalline cellulose micropill is added into the medicine-containing solutionCore (commercial production of CELPHERE by Japanese Xudi chemical industry)
Model: SCP-100, D90 is 100 μm), the stirring speed is reduced to 20rpm, stirring is stopped after 5 hours, and standing is carried out for 2 hours; filtering the above medicinal liquid with 10 μm pore diameter filter paper/membrane, collecting medicinal pellets (wet), placing in fluidized bed, setting air inlet temperature at 60deg.C, starting air blast, drying, stopping when material temperature reaches 50deg.C, and obtaining 235 parts of medicinal pellets (dry);
the measured moisture content of the drug-containing pellets is less than 2%, the friability is 0, and the weight gain of the drug-containing pellets relative to the microcrystalline cellulose pellet core is 57%.
S2, preparing sustained-release pellets: 20 parts of Astand Ethyl Cellulose (EC) Aqualon was taken
(model: N14) and 2 parts of triethyl citrate (TEC), adding into 378 parts of 80% ethanol solution, stirring at 300rpm to dissolve completely to obtain coating solution; 200 parts of the drug-containing pellets (dried) prepared in the example are taken and put into a fluidized bed with a bottom spraying device, and coating liquid is sprayed into the fluidized bed for coating at the air inlet temperature of 45 ℃; after all coating liquid is sprayed, the air inlet temperature is regulated to be 60 ℃, and the drying is continued for 30 minutes, thus obtaining 216 parts of dextromethorphan sustained-release pellets (the coating weight gain is 8%).
A dextromethorphan suspension comprising: 216 parts of dextromethorphan sustained-release pellets, 20 parts of xanthan gum, 6 parts of citric acid, 5 parts of aspartame, 1 part of methylparaben, 1 part of lemon essence, 1 part of lemon yellow and 250 parts of purified water.
The preparation method comprises the following steps: firstly, adding 20 parts of xanthan gum into 250 parts of purified water, stirring to dissolve the xanthan gum to form viscous liquid, then sequentially adding 6 parts of citric acid, 5 parts of aspartame, 1 part of methylparaben, 1 part of lemon essence and 1 part of lemon yellow, and stirring to dissolve completely; finally, 216 parts of dextromethorphan sustained-release pellets prepared in the embodiment are taken and put into the sustained-release pellets, and stirred for 30 minutes at 300rpm, so that uniform suspension is formed; and finally filling the mixture into an HDPE bottle, and capping to obtain a finished product.
Example 2
The dextromethorphan sustained-release pellet is prepared by the following steps:
s1, preparing a drug-containing pellet: adding 300 parts of dextromethorphan hydrobromide bulk drug into 300 parts of 80% ethanol solution, and stirring for 30 minutes at 300rpm to obtain a drug-containing solution; then, 150 parts of self-made microcrystalline cellulose pellet cores are added, the stirring speed is reduced to 15rpm, stirring is stopped after 5 hours, and standing is carried out for 2 hours; filtering the above medicinal liquid with filter paper/membrane with 50 μm pore diameter, collecting the medicinal pellets (wet), placing in fluidized bed, setting air inlet temperature at 60deg.C, starting air blast, starting drying, stopping until the material temperature reaches 50deg.C, and obtaining 240 parts of medicinal pellets (dry);
the measured moisture of the drug-containing pellets is within 1.5%, the friability is 0, and the weight gain of the drug-containing pellets relative to the microcrystalline cellulose pellet core is 60%.
S2, preparing sustained-release pellets: adding 25 parts of ethyl cellulose and 2 parts of triethyl citrate into 243 parts of 75% ethanol, and stirring to completely dissolve to obtain coating liquid with solid content of 10%; 240 parts of the drug-containing pellets (dried) prepared in the example are taken and put into a fluidized bed provided with a bottom spraying device, and the air quantity is controlled at 1000m at the air inlet temperature of 45 DEG C 3 And/h, when the temperature of the material reaches above 42 ℃, the peristaltic pump can be started, the rotating speed is kept at 20rpm, the rotating speed of the peristaltic pump can be regulated according to the temperature of the material, and the temperature of the material in the whole coating process is not lower than 32 ℃. After the coating liquid is consumed, a peristaltic pump is closed, the air inlet temperature is regulated to 60 ℃, and the drying is continued for 35 minutes, so that 260 parts of sustained-release pellets (the coating weight gain is 8.0%) are obtained.
Wherein, the microcrystalline cellulose pellet core is prepared by the following steps: adding 100 parts of microcrystalline cellulose into 300 parts of purified water, homogenizing under 1200bar pressure by a high-pressure homogenizer, vacuum filtering to obtain a microcrystalline cellulose filter cake containing water with water content of 40%, and drying by using a fluidized bed; finally, putting the mixture into an extrusion spheronizer, and preparing the microcrystalline cellulose pellet core by using a section plate with the thickness of 0.1 mm. The particle size distribution D90 of the pellet cores was 130 μm as measured by a laser particle sizer, and the friability was 0 as measured.
A dextromethorphan suspension comprising: 260 parts of dextromethorphan sustained-release pellets prepared in the embodiment, 20 parts of xanthan gum, 8 parts of citric acid, 5 parts of sucralose, 5 parts of sodium benzoate, 1 part of strawberry essence, 1 part of carmine and 200 parts of purified water.
The preparation method comprises the following steps: adding 20 parts of xanthan gum into 200 parts of purified water, stirring to dissolve to form viscous liquid, sequentially adding 8 parts of citric acid, 5 parts of sucralose, 5 parts of sodium benzoate, 1 part of strawberry essence and 1 part of carmine, and stirring to dissolve completely; finally, 260 parts of dextromethorphan slow release pellets prepared in the embodiment are taken and put into the slow release pellets, and stirred for 30 minutes at 300rpm, so that uniform suspension is formed; and finally filling the mixture into a white or brown HDPE bottle, and capping to obtain a finished product.
Example 3
The dextromethorphan sustained-release pellet is prepared by the following steps:
s1, preparing a drug-containing pellet: the same as in example 2;
s2, preparing sustained-release pellets: 25 parts of methacrylic acid-methyl acrylate copolymer (1:1) and 3 parts of diethyl phthalate are added into 205 parts of 80% ethanol, and the mixture is stirred to be completely dissolved, so as to obtain a coating liquid with the solid content of 12%. Then 240 parts of drug-containing pellets (dry) are taken and put into a fluidized bed with a bottom spraying device, the air inlet temperature is set to be 45 ℃, and the air quantity is controlled to be 800m 3 And/h, when the temperature of the material reaches above 42 ℃, the peristaltic pump can be started, the rotating speed is kept at 10rpm, the rotating speed of the peristaltic pump can be regulated according to the temperature of the material, and the temperature of the material in the whole coating process is not lower than 32 ℃. After the coating liquid is consumed, a peristaltic pump is closed, the air inlet temperature is regulated to 60 ℃, the drying is continued for 30 minutes, and 255 parts of slow-release pellets (the coating weight gain is 6.25%) are obtained.
The dextromethorphan suspension is prepared by replacing dextromethorphan sustained-release pellets with dextromethorphan sustained-release pellets prepared in the embodiment, and other formula compositions and preparation methods are the same as those in the embodiment 1.
Comparative example 1
The dextromethorphan sustained-release pellet is prepared by the following steps:
s1, preparing a drug-containing pellet: taking 300 parts of dextromethorphan hydrobromide bulk drug, adding the bulk drug into 300 parts of 50% methanol solution, and stirring for 30 minutes at 300 rpm; then, 150 parts of self-made microcrystalline cellulose pellet cores are added, the stirring speed is reduced to 15rpm, stirring is stopped after 5 hours, and standing is carried out for 2 hours; filtering the above medicinal liquid with filter paper/membrane with 50 μm pore diameter, collecting the medicinal pellets (wet), placing in fluidized bed, setting air inlet temperature at 60deg.C, starting air blast, starting drying, stopping when material temperature reaches 50deg.C, and obtaining 247.5 parts of medicinal pellets (dry);
the measured moisture of the drug-containing pellets is within 3%, the friability is 0.2%, and the weight gain of the drug-containing pellets relative to the microcrystalline cellulose pellet core is 65%.
Wherein, microcrystalline cellulose micropellet cores were self-made in the same manner as in example 2.
S2, preparing sustained-release pellets: the same as in example 2.
Performance test:
the in vitro release curves of dextromethorphan suspensions prepared in examples 2 and 3 of the invention are measured by referring to the second method of the general rule 0931 in the year 2020 of Chinese pharmacopoeia: precisely measuring about 10ml of a sample, placing the sample in 900ml of degassed phosphate buffer with pH of 6.8, and rotating at 100rpm and 37 ℃; when the sample is put into the container, the timing is started, 10ml is sampled at a set time point, simultaneously, the isothermal and equal-volume release medium is supplemented, the sample solution is obtained by filtering, and the content of dextromethorphan is detected by the sample at each time point.
Examples 2, 3 in vitro release profiles of dextromethorphan suspensions are shown in fig. 4, it can be seen that the release of the drug in dextromethorphan suspensions prepared according to the present invention is free of burst release; from the accumulated release, the release curve is more gentle, approaching "zero order release"; the total release time is about 10-12 hours, and compared with the conventional dextromethorphan preparation, the drug release period is prolonged by almost one time, and the good in-vitro release curve is in-vivo drug release and maintains a good drug effect basis.
The key point of the dextromethorphan suspension provided by the invention, which has a good in-vitro release curve, is that: (1) Microcrystalline cellulose micropellet cores with rich pores are used as drug-carrying materials, and an adsorption drying method is used, so that the drug loading capacity is improved; (2) The drug-containing pellets are coated by adopting a material which is slightly soluble, indissolvable or water insoluble in water as a slow-release coating material and matching with a water-soluble plasticizer to regulate the release rate of the drug.
The foregoing is only a preferred embodiment of the present invention, but the scope of the present invention is not limited thereto, and any person skilled in the art, who is within the scope of the present invention, should make equivalent substitutions or modifications according to the technical scheme of the present invention and the inventive concept thereof, and should be covered by the scope of the present invention.
Claims (10)
1. The dextromethorphan sustained-release pellet is characterized in that the preparation method comprises the following steps: s1, taking dextromethorphan hydrobromide as a raw material drug and taking a microcrystalline cellulose pellet core as a drug carrying material, and obtaining a drug-containing pellet with the drug contained in the interior and the surface by adopting an adsorption drying method; s2, coating the drug-containing pellets by using a slightly soluble, insoluble or water-insoluble material in water as a slow-release coating material and using a water-soluble material as a plasticizer to obtain the dextromethorphan slow-release pellets.
2. The dextromethorphan sustained release pellet of claim 1, wherein the weight ratio of microcrystalline cellulose pellet core to dextromethorphan hydrobromide bulk drug is 1-2:2.
3. Dextromethorphan sustained release pellets according to claim 1 or 2 wherein the microcrystalline cellulose pellet core D90 has a particle size of 100-200 μm.
4. Dextromethorphan sustained release pellets as set forth in any one of claims 1-3 wherein the microcrystalline cellulose pellet core is selected from a commercially available finished product or is self-made; preferably, the preparation method of the microcrystalline cellulose pellet core comprises the following steps: adding microcrystalline cellulose into water, and homogenizing to obtain an aqueous microcrystalline cellulose filter cake; and drying the microcrystalline cellulose filter cake, and adopting an extrusion spheronization method.
5. The dextromethorphan sustained-release pellet according to any one of claims 1-4, wherein the moisture of the drug-containing pellet is less than or equal to 3%; the weight of the drug-containing micropellets is increased by 55-65% relative to the microcrystalline cellulose micropellet core.
6. The dextromethorphan sustained release pellet as recited in any one of claims 1-5, wherein the adsorption drying process specifically comprises: dissolving dextromethorphan hydrobromide bulk drug in a solvent to obtain a drug-containing solution; placing microcrystalline cellulose pellet core into the drug-containing solution, stirring for 4-6h, filtering and drying to obtain drug-containing pellet; preferably, the solvent is 50-80% ethanol; preferably, the concentration of the drug-containing solution is 10-50%; preferably, the stirring rate is 10-20rpm.
7. Dextromethorphan sustained-release pellets as recited in any one of claims 1-6 wherein the sustained-release coating material is selected from the group consisting of one or more of celluloses, polyacrylic resins and derivatives thereof, polydimethylsiloxanes and analogs thereof; preferably, the cellulose-based coating material is cellulose acetate or ethylcellulose.
8. Dextromethorphan sustained release pellets as set forth in any one of claims 1-7 wherein the plasticizer is selected from the group consisting of polyethylene glycol, triethyl citrate, diethyl phthalate, and combinations thereof; preferably, the coating is weighted 5-8%.
9. Dextromethorphan suspension comprising dextromethorphan slow release pellets according to any one of claims 1-8.
10. Dextromethorphan suspension according to claim 9, comprising, in parts by weight: 200-300 parts of dextromethorphan sustained-release pellets, 20-30 parts of thickening agent, 6-10 parts of pH regulator, 5-10 parts of corrigent, 1-5 parts of bacteriostat and 200-300 parts of water; preferably, the food additive also comprises 1-2 parts of edible essence and 1-5 parts of edible pigment.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211705125.5A CN116115584A (en) | 2022-12-29 | 2022-12-29 | Dextromethorphan sustained-release pellets and suspension |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211705125.5A CN116115584A (en) | 2022-12-29 | 2022-12-29 | Dextromethorphan sustained-release pellets and suspension |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN116115584A true CN116115584A (en) | 2023-05-16 |
Family
ID=86302150
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202211705125.5A Pending CN116115584A (en) | 2022-12-29 | 2022-12-29 | Dextromethorphan sustained-release pellets and suspension |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN116115584A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN117017911A (en) * | 2023-08-15 | 2023-11-10 | 山东则正医药技术有限公司 | Dextromethorphan hydrobromide sustained-release suspension and preparation method thereof |
-
2022
- 2022-12-29 CN CN202211705125.5A patent/CN116115584A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN117017911A (en) * | 2023-08-15 | 2023-11-10 | 山东则正医药技术有限公司 | Dextromethorphan hydrobromide sustained-release suspension and preparation method thereof |
| CN117017911B (en) * | 2023-08-15 | 2024-06-07 | 山东则正医药技术有限公司 | Dextromethorphan hydrobromide sustained-release suspension and preparation method thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| RU2072840C1 (en) | Solid medicinal form of the prolonged action for cardiovascular disease treatment | |
| EP0797991B1 (en) | Extended release formulation containing venlafaxine | |
| CN1886119B (en) | Pantoprazole multiparticulate formulations | |
| CA2473200C (en) | Extended release compositions comprising as active compound venlafaxine hydrochloride | |
| CN101495103B (en) | Pharmaceutical preparation for oral administration with controlled drug release in the small intestine colon and process of preparation thereof | |
| EP3498264B1 (en) | Pharmaceutical preparation for oral administration with controlled dissolution rate, the preparation comprising tamsulosin hydrochloride-containing sustained-release pellets | |
| CN101574323B (en) | Migltol microcapsule tablet and preparation method thereof | |
| JP2002520351A (en) | Pellets having a core coated with an antibacterial / mold agent and a polymer | |
| AU1300399A (en) | Extended release formulation | |
| CN116115584A (en) | Dextromethorphan sustained-release pellets and suspension | |
| EP0083372B1 (en) | Sustained release theophyline | |
| JP2004513182A (en) | Oral formulation for specific colon delivery and method for producing the same | |
| CN1994285B (en) | Sustained release micro-pellet of guaifenesin and preparation process thereof | |
| CN102626428A (en) | Ginkgo leaf extract osmotic pump controlled-release preparation and preparation method thereof | |
| CN106963736A (en) | Dextromethorphan hydrobromide sustained-release dry suspensoid agent and preparation method thereof | |
| EP1839649A1 (en) | Coated formulations for tolterodine | |
| CN103054813A (en) | Azithromycin oral sustained-release dry suspension and preparation method thereof | |
| CN101756982B (en) | Artesunate compound medicine composition with improved mouth feeling and high stability | |
| CN114699386B (en) | Azithromycin composition and preparation method thereof | |
| CN101120931A (en) | Bezafibrate sustained-release composition | |
| CN105902500A (en) | Mesalazine enteric positioned controlled-release preparation and preparation method thereof | |
| CN101869544A (en) | Ambroxol hydrochloride controlled release suspension and preparation method thereof | |
| CN112472715B (en) | Sodium bicarbonate enteric capsule and preparation method thereof | |
| CN102657615A (en) | Vincamine sustained-release pellet preparation and preparation method thereof | |
| CN104644565B (en) | A kind of Doxycycline Hyclate pastille piller and preparation method thereof |
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 |