Method for optimizing disintegration performance of eslicarbazepine acetate tablets

Abstract

The invention relates to the technical field of pharmaceutical preparations, discloses a disintegration performance optimization method for eslicarbazepine acetate tablets, and solves the problems that when an existing eslicarbazepine acetate tablet disintegrant is used, the efficiency is low during timed and quantitative release of drugs and disintegration of drug tablets, the efficient release of the drugs is greatly influenced, and the disintegration performance of the drugs is influenced. And the eslicarbazepine acetate is not easy to absorb by a user. The disintegration efficiency of the medicine tablets can be improved, and efficient dilution of the medicine is greatly improved.

Description

Technical Field

[0001] The invention relates to the technical field of pharmaceutical preparations, in particular to a method for optimizing the disintegration performance of eslicarbazepine acetate tablets. Background Art

[0002] Eslicarbazepine acetate is a derivative of the anti-epileptic drug carbamazepine. It was developed and marketed by the Portuguese pharmaceutical company Bial. It is a new anti-epileptic drug mainly used to treat epilepsy, affective brain dysfunction, and pain and neurological alternation in degenerative and post-ischemic diseases. It was approved for sale in Europe in 2009 under the trade names Zebinix and Exalief. Eslicarbazepine acetate is an anti-epileptic drug developed to improve the efficacy and tolerance of carbamazepine and oxcarbazepine. It is a prodrug of the third-generation CBZ drug S-licarbazepine and an active metabolite of OXC. It is a new type of sodium ion channel blocker that specifically acts on ion channels, preventing them from returning to an active state and thus reducing their repeated activation efficiency.

[0003] Controlled-release tablets are preparations that can control the release rate of drugs in the body so that they are released according to a predetermined program. Starch-based disintegrants play a key role in controlled-release tablets. Immediate-release tablets are preparations that can quickly disintegrate and release drugs so that the drugs reach an effective concentration in a short period of time. Starch-based disintegrants also play an important role in immediate-release tablets.

[0004] For example, application number CN201710140262.1 discloses a method for preparing eslicarbazepine acetate tablets, wherein the raw materials of the eslicarbazepine acetate tablets are: 400 parts by weight of eslicarbazepine acetate, 28 to 32 parts by weight of cross-linked sodium carboxymethyl cellulose, 34 to 36 parts by weight of povidone, and 3 to 4 parts by weight of magnesium stearate; wherein 16 parts by weight of cross-linked sodium carboxymethyl cellulose is added internally, and the remainder is added externally; 18 parts by weight of povidone is added internally, and the remainder is added externally; the preparation method comprises: I. crushing of active ingredients, II. mixing of granulation materials, III. granulation, IV. drying, V. granulation, VI. mixing of external auxiliary materials, and VII. tableting. The existing disintegrants for eslicarbazepine acetate tablets are inefficient in terms of drug timing, quantitative release, and disintegration of drug tablets when used, which greatly affects the efficient release of the drug and is not conducive to the absorption of eslicarbazepine acetate by users.

[0005] In view of the above problems, a method for optimizing the disintegration performance of eslicarbazepine acetate tablets is proposed. Summary of the invention

[0006] The object of the present invention is to provide a method for optimizing the disintegration performance of eslicarbazepine acetate tablets. The device is used to work, thereby solving the problem that the existing eslicarbazepine acetate tablet disintegrant is inefficient in the timing and quantitative release of the drug and the disintegration of the drug tablets, which greatly affects the efficient release of the drug and is not conducive to the absorption of eslicarbazepine acetate by users.

[0007] To achieve the above object, the present invention provides the following technical solution: a method for optimizing the disintegration performance of eslicarbazepine acetate tablets, comprising the following optimization preparation steps:

[0008] Step 1: First, prepare the raw materials, take a certain amount of eslicarbazepine acetate, polyvinyl alcohol and hydroxyethyl cellulose, and put them into the inside of the grinder so that the crushed particles of the raw materials are less than 50 microns;

[0009] Step 2: using sugar alcohol, cross-linked polyvinyl pyrrolidone and water-insoluble film-forming polymer, the raw materials are put into a stirring mill for mixing, and the raw materials are filtered to ensure the subsequent disintegrant manufacturing effect;

[0010] Step 3, mixing the eslicarbazepine acetate and hydroxyethyl cellulose obtained in step 1, and mixing polyvinyl alcohol with water, so that the proportion of the polyvinyl alcohol solution is 10% to 15%;

[0011] Step 4: mixing the polyvinyl alcohol solution with eslicarbazepine acetate and hydroxyethyl cellulose, and performing a mixing operation by a temperature control machine so that the water content in the solvent is reduced to less than or equal to 2%;

[0012] Step 5: Mix the dry particles obtained in step 4, the sugar alcohol obtained in step 2, the cross-linked polyvinyl pyrrolidone and the water-insoluble film-forming polymer, and sieve through a 48-mesh sieve to obtain granulated dry particles;

[0013] Step 6: compress the mixture obtained in step 5 to obtain tablets, thereby completing the preparation of eslicarbazepine acetate tablets.

[0014] Preferably, the pulverizing time of the pulverizer in step one is forty minutes to fifty-five minutes, and the dust generated by the pulverizing is reduced by spraying mist water to improve the drug recovery efficiency.

[0015] Preferably, the water-insoluble film-forming polymer in step 2 is a mixture of ethyl cellulose, which is a high molecular weight film material that is insoluble in water and is commonly used for film coating.

[0016] Preferably, the step of performing the mixing operation in step 3 comprises the following steps: first, eslicarbazepine acetate and hydroxyethyl cellulose are mixed for a mixing time of eight to thirteen minutes, and the rotation speed is controlled to thirty revolutions per minute to obtain a granulated material. By setting the above steps, the disintegration speed of the tablets is shortened from the original fifteen minutes to five minutes.

[0017] Preferably, the mixing operation in step 3 can be performed with a loading amount of 600 to 750 grams each time, and the mixing can be performed three times each time, so that eslicarbazepine acetate and hydroxyethyl cellulose can be fully mixed, so that the disintegration rate of the overall drug is greatly improved.

[0018] Preferably, the controlled temperature in the temperature controller in step 4 is 70 to 75 degrees, the mixing time is 5 to 8 minutes, and the mixing frequency is 25 to 36 Hz.

[0019] Preferably, a screening machine is used for screening in step five, the purpose of which is to recycle and crush items with larger particles. The vibration frequency of the screening machine is 50 Hz to 70 Hz, and 400 g to 500 g of material can be fed each time, and each time takes three minutes.

[0020] Preferably, the tableting force in step six is ​​15 to 20 kilonewtons, the tablet hardness is 20 to 30 kilograms force, the drug disintegrates in less than three minutes after contact with saliva in the oral cavity, and more than 80% of the total amount is dissolved in nine minutes.

[0021] Preferably, the eslicarbazepine acetate tablets prepared by the preparation method contain 470 mg of eslicarbazepine acetate per tablet, and the average tablet weight is 520 to 580 mg, which improves the disintegration rate of eslicarbazepine acetate and the absorption rate of the human body.

[0022] Compared with the prior art, the present invention has the following beneficial effects:

[0023] 1. The present application proposes a method for optimizing the disintegration performance of eslicarbazepine acetate tablets, which solves the problem that the existing eslicarbazepine acetate tablet disintegrant is inefficient in the timing and quantitative release of the drug and the disintegration of the drug tablets when in use, which greatly affects the efficient release of the drug and is not conducive to the user's absorption of eslicarbazepine acetate. The quantitatively mixed raw materials of eslicarbazepine acetate, polyvinyl alcohol and hydroxyethyl cellulose can be crushed, and the crushing time of the crusher is 40 minutes to 55 minutes. The dust generated by the crushing is reduced by spraying mist water, thereby improving the drug recovery efficiency and avoiding the waste of raw materials. In addition, the water mist humidification method can also be used to reduce the dust generated by the crushing. The mixing efficiency of the raw materials can be improved. Sugar alcohol, cross-linked polyvinyl pyrrolidone and water-insoluble film-forming polymers are used. The raw materials are put into a stirring pulverizer for mixing, and the raw materials are filtered to ensure the subsequent manufacturing effect of the disintegrant. The water-insoluble film-forming polymer includes a mixture of ethyl cellulose, wherein the ethyl cellulose is mainly used as a tablet binder for preparing sustained-release preparations and controlled-release preparations to improve the stability and bioavailability of the drug. The setting of ethyl cellulose can greatly improve the disintegration rate of eslicarbazepine acetate tablets to facilitate the patient's absorption of the drug, thereby achieving the improvement of the efficiency of the disintegration of the drug tablets and greatly improving the efficient dilution of the drug.

[0024] 2. The present application proposes a method for optimizing the disintegration performance of eslicarbazepine acetate tablets, which solves the problem that the existing eslicarbazepine acetate tablet disintegrant has many operations during the processing and manufacturing process, and needs to add additional drugs for reaction, which is not conducive to the production of eslicarbazepine acetate tablet disintegrants. Eslicarbazepine acetate, polyvinyl alcohol, hydroxyethyl cellulose and water are mixed, sugar alcohol, cross-linked polyvinyl pyrrolidone and water-insoluble film-forming polymer are crushed and added to a crushing mixer, and a mixing operation is performed by a temperature controller. The control temperature in the temperature controller is 70 to 75 degrees, the mixing time is 5 minutes to 8 minutes, and the mixing frequency is 25 Hz to 36 Hz, which can greatly improve the mixing effect and reduce the water content in the solvent to The dry granules obtained in step 4 and the sugar alcohol, cross-linked polyvinyl pyrrolidone and water-insoluble film-forming polymer obtained in step 2 are mixed, and sieved through a 48-mesh sieve to obtain dry granules after granulation, and the obtained raw materials are compressed to obtain compressed tablets, thereby completing the preparation of eslicarbazepine acetate tablets, and the tableting force is 15 to 20 kilonewtons, and the tablet hardness is 20 to 30 kilograms. The obtained eslicarbazepine acetate tablets contain 470 mg of eslicarbazepine acetate per tablet, and the drug disintegrates within less than three minutes of contact with saliva in the oral cavity, and more than 80% of the total amount is dissolved in nine minutes, thereby achieving the ability to improve the preparation rate of the disintegrant for eslicarbazepine acetate tablets and also increasing the content of eslicarbazepine acetate per tablet. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] Figure 1 It is a schematic diagram of the overall process of the present invention;

[0026] Figure 2 is a mixing flow chart of the polyvinyl alcohol solution of the present invention;

[0027] Figure 3 is a mixing flow chart of cross-linked polyvinyl pyrrolidone of the present invention;

[0028] Figure 4 The present invention is a flow chart of the composition of the water-insoluble film-forming polymer. DETAILED DESCRIPTION

[0029] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0030] In order to further understand the content of the present invention, the present invention is described in detail in conjunction with the accompanying drawings.

[0031] Combination Figure 1-Figure 3 , a method for optimizing the disintegration performance of eslicarbazepine acetate tablets, comprising the following optimization preparation steps:

[0032] Step 1: First, prepare the raw materials, take a certain amount of eslicarbazepine acetate, polyvinyl alcohol and hydroxyethyl cellulose, and put them into the inside of the grinder so that the crushed particles of the raw materials are less than 50 microns;

[0033] Step 2: using sugar alcohol, cross-linked polyvinyl pyrrolidone and water-insoluble film-forming polymer, the raw materials are put into a stirring mill for mixing, and the raw materials are filtered to ensure the subsequent disintegrant manufacturing effect;

[0034] Step 3, mixing the eslicarbazepine acetate and hydroxyethyl cellulose obtained in step 1, and mixing polyvinyl alcohol with water, so that the proportion of the polyvinyl alcohol solution is 10% to 15%;

[0035] Step 4: mixing the polyvinyl alcohol solution with eslicarbazepine acetate and hydroxyethyl cellulose, and performing a mixing operation by a temperature control machine so that the water content in the solvent is reduced to less than or equal to 2%;

[0036] Step 5: Mix the dry particles obtained in step 4, the sugar alcohol obtained in step 2, the cross-linked polyvinyl pyrrolidone and the water-insoluble film-forming polymer, and sieve through a 48-mesh sieve to obtain granulated dry particles;

[0037] Step 6: compress the mixture obtained in step 5 to obtain tablets, thereby completing the preparation of eslicarbazepine acetate tablets.

[0038] The pulverizing time of the pulverizer in step one is 40 to 55 minutes, and the dust generated by the pulverizing is reduced by spraying mist water to improve the drug recovery efficiency.

[0039] The water-insoluble film-forming polymer in step 2 is a mixture of ethyl cellulose, which is a high molecular film material that is insoluble in water and is commonly used for film coating.

[0040] The step of mixing operation in step 3 includes the following steps: first, eslicarbazepine acetate and hydroxyethyl cellulose are mixed for a mixing time of eight to thirteen minutes, and the rotation speed is controlled to thirty revolutions per minute to obtain a granulated material. Through the setting of the above steps, the disintegration speed of the tablets is shortened from the original fifteen minutes to five minutes.

[0041] The mixing operation in step 3 can be performed with a loading amount of 600 to 750 grams each time, and the mixing can be performed three times each time, so that the eslicarbazepine acetate and the hydroxyethyl cellulose can be fully mixed, so that the disintegration rate of the overall drug is greatly improved.

[0042] The controlled temperature in the temperature control machine in step 4 is 70 to 75 degrees, the mixing time is 5 minutes to 8 minutes, and the mixing frequency is 25 Hz to 36 Hz.

[0043] In step five, a screening machine is used for screening in order to recycle and crush items with larger particles. The vibration frequency of the screening machine is 50 Hz to 70 Hz. It can feed 400 grams to 500 grams each time, and each time takes three minutes.

[0044] The tableting force in step six is ​​15 to 20 kilonewtons, and the tablet hardness is 20 to 30 kilograms of force. The drug disintegrates in less than three minutes after contacting with saliva in the oral cavity, and more than 80% of the total amount is dissolved in nine minutes.

[0045] The eslicarbazepine acetate tablets prepared by the preparation method contain 470 mg of eslicarbazepine acetate per tablet, and the average tablet weight is 520 to 580 mg, thereby increasing the disintegration rate of eslicarbazepine acetate and the absorption rate of the human body.

[0046] The present invention will be further described below in conjunction with the embodiments.

[0047] Embodiment 1:

[0048] In order to solve the problem that the existing eslicarbazepine acetate tablet disintegrant has low efficiency in drug timing, quantitative release and disintegration of drug tablets, which greatly affects the efficient release of the drug and is not conducive to the absorption of eslicarbazepine acetate by users, the present embodiment discloses the following technical solutions, specifically as follows Figure 1-Figure 3 As shown, the quantitatively mixed raw materials of eslicarbazepine acetate, polyvinyl alcohol and hydroxyethyl cellulose can be pulverized, the pulverizing time of the pulverizer is 40 minutes to 55 minutes, and the dust generated by the pulverization is reduced by spraying mist water, thereby improving the drug recovery efficiency and avoiding the waste of raw materials. The mixing efficiency of the raw materials can also be improved by humidifying with water mist. Sugar alcohol, cross-linked polyvinyl pyrrolidone and water-insoluble film-forming polymer are used, and the raw materials are put into the inside of the stirring pulverizer for mixing, and the raw materials are filtered to ensure the subsequent manufacturing efficiency of the disintegrant. The invention relates to a method for preparing a sustained-release preparation and a controlled-release preparation, wherein the water-insoluble film-forming polymer comprises a mixture of ethyl cellulose, wherein the ethyl cellulose is mainly used as a tablet binder, and is used to prepare sustained-release preparations and controlled-release preparations, so as to improve the stability and bioavailability of the drug. The disintegration rate of the eslicarbazepine acetate tablet can be greatly improved by the setting of the ethyl cellulose, so as to facilitate the absorption of the drug by the patient, so that the time for the drug to disintegrate after contacting with saliva in the oral cavity for fifteen minutes is shortened to less than three minutes, thereby achieving the improvement of the disintegration efficiency of the drug tablet and greatly improving the efficient dilution of the drug.

[0049] At the same time, in order to solve the problem that the existing eslicarbazepine acetate tablet disintegrant has many operations during the processing and manufacturing process, and additional drugs need to be added for reaction, which is not conducive to the production of the eslicarbazepine acetate tablet disintegrant, the present embodiment also discloses the following scheme: eslicarbazepine acetate, polyvinyl alcohol, hydroxyethyl cellulose and water are mixed, sugar alcohol, cross-linked polyvinyl pyrrolidone and water-insoluble film-forming polymer are crushed and added to a crushing mixer, and a mixing operation is performed by a temperature controller. The control temperature in the temperature controller is 70 to 75 degrees, the mixing time is 5 minutes to 8 minutes, and the mixing frequency is 25 Hz to 36 Hz, which can greatly improve the mixing effect, so that the water content in the solvent is reduced to less than or equal to 100 The method comprises the steps of: mixing the dry granules obtained in step 4 and the sugar alcohol, cross-linked polyvinyl pyrrolidone and water-insoluble film-forming polymer obtained in step 2, and granulating the granules through a 48-mesh sieve to obtain dry granules after granulation, and compressing the obtained raw materials to obtain compressed tablets, thereby completing the preparation of eslicarbazepine acetate tablets, and the tableting force is 15 to 20 kilonewtons, and the tablet hardness is 20 to 30 kilograms of force. The obtained eslicarbazepine acetate tablets contain 470 mg of eslicarbazepine acetate per tablet, and the medicament disintegrates within less than three minutes after contacting with saliva in the oral cavity, and more than 80% of the total amount is dissolved within nine minutes, thereby achieving the ability to improve the preparation rate of the disintegrant for eslicarbazepine acetate tablets, and also improving the content of eslicarbazepine acetate per tablet.

[0050] It should be noted that, in this article, relational terms such as first and second, etc. are only used to distinguish one entity or operation from another entity or operation, and do not necessarily require or imply any such actual relationship or order between these entities or operations. Moreover, the terms "include", "comprise" or any other variants thereof are intended to cover non-exclusive inclusion, so that a process, method, article or device including a series of elements includes not only those elements, but also other elements not explicitly listed, or also includes elements inherent to such process, method, article or device.

[0051] Although embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that various changes, modifications, substitutions and variations may be made to the embodiments without departing from the principles and spirit of the present invention, and that the scope of the present invention is defined by the appended claims and their equivalents.

Claims

1. A method for optimizing the disintegration performance of eslicarbazepine acetate tablets, characterized in that: The method comprises the following optimized preparation steps: Step 1: First, prepare the raw materials, take a certain amount of eslicarbazepine acetate, polyvinyl alcohol and hydroxyethyl cellulose, and put them into the inside of the grinder so that the crushed particles of the raw materials are less than 50 microns; Step 2: using sugar alcohol, cross-linked polyvinyl pyrrolidone and water-insoluble film-forming polymer, the raw materials are put into a stirring mill for mixing, and the raw materials are filtered to ensure the subsequent disintegrant manufacturing effect; Step 3, mixing the eslicarbazepine acetate and hydroxyethyl cellulose obtained in step 1, and mixing polyvinyl alcohol with water, so that the proportion of the polyvinyl alcohol solution is 10% to 15%; Step 4: mixing the polyvinyl alcohol solution with eslicarbazepine acetate and hydroxyethyl cellulose, and performing a mixing operation by a temperature control machine so that the water content in the solvent is reduced to less than or equal to 2%; Step 5: Mix the dry particles obtained in step 4, the sugar alcohol obtained in step 2, the cross-linked polyvinyl pyrrolidone and the water-insoluble film-forming polymer, and sieve through a 48-mesh sieve to obtain granulated dry particles; Step 6: compress the mixture obtained in step 5 to obtain tablets, thereby completing the preparation of eslicarbazepine acetate tablets.

2. The method for optimizing the disintegration performance of eslicarbazepine acetate tablets according to claim 1, characterized in that: The pulverizing time of the pulverizer in step 1 is 40 minutes to 55 minutes, and the dust generated by the pulverization is reduced by spraying mist water to improve the drug recovery efficiency.

3. The method for optimizing the disintegration performance of eslicarbazepine acetate tablets according to claim 1, characterized in that: The water-insoluble film-forming polymer in step 2 is a mixture of ethyl cellulose, which is a high molecular weight film material that is insoluble in water and is commonly used for film coating.

4. The method for optimizing the disintegration performance of eslicarbazepine acetate tablets according to claim 1, characterized in that: The step of mixing operation in step 3 includes the following steps: first, eslicarbazepine acetate and hydroxyethyl cellulose are mixed for a mixing time of eight to thirteen minutes, and the rotation speed is controlled to thirty revolutions per minute to obtain a granulated material. Through the setting of the above steps, the disintegration speed of the tablets is shortened from the original fifteen minutes to five minutes.

5. The method for optimizing the disintegration performance of eslicarbazepine acetate tablets according to claim 4, characterized in that: The mixing operation in step 3 can be performed with a loading amount of 600 to 750 grams each time, and the mixing can be performed three times each time, so that eslicarbazepine acetate and hydroxyethyl cellulose can be fully mixed, so that the disintegration rate of the overall drug is greatly improved.

6. The method for optimizing the disintegration performance of eslicarbazepine acetate tablets according to claim 1, characterized in that: The controlled temperature in the temperature control machine in step 4 is 70 to 75 degrees, the mixing time is 5 to 8 minutes, and the mixing frequency is 25 Hz to 36 Hz.

7. The method for optimizing the disintegration performance of eslicarbazepine acetate tablets according to claim 1, characterized in that: In the step five, a screening machine is used for screening, the purpose of which is to recycle and crush items with larger particles. The vibration frequency of the screening machine is 50 Hz to 70 Hz, and 400 g to 500 g of material can be fed each time, and each time takes three minutes.

8. The method for optimizing the disintegration performance of eslicarbazepine acetate tablets according to claim 1, characterized in that: The tableting force in step six is ​​15 to 20 kN, and the tablet hardness is 20 to 30 kilograms. The drug disintegrates in less than three minutes after contact with saliva in the oral cavity, and more than 80% of the total amount is dissolved in nine minutes.

9. The method for optimizing the disintegration performance of eslicarbazepine acetate tablets according to claim 1, characterized in that: The eslicarbazepine acetate tablets prepared by the preparation method contain 470 mg of eslicarbazepine acetate per tablet, and the average tablet weight is 520 to 580 mg, thereby increasing the disintegration rate of eslicarbazepine acetate and the absorption rate of the human body.

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