LU600993B1

LU600993B1 - Process for preparing sustained-release oral preparations based on microencapsulation technology

Info

Publication number: LU600993B1
Application number: LU600993A
Authority: LU
Inventors: Ai Ning Wang
Original assignee: Winner Rise Trade Ltd
Priority date: 2025-04-08
Filing date: 2025-04-08
Publication date: 2025-10-08

Abstract

The present invention relates to the field of pharmaceutical technology, and discloses a slow-release oral preparation process based on microencapsulation technology, after selecting a drug, it is necessary to carry out a fine pre-treatment operation, using advanced crushing technology, with the help of professional equipment such as an airflow crusher, to carry out crushing operations on the ibuprofen, metformin hydrochloride and other medicines, and in the process of crushing, the use of high-pressure airflow of the powerful impact, the particles of the drug will be gradually refined. The technology, the drug can achieve a slow and sustained release in the body, thus significantly extending its action time, significantly reducing the frequency of drug administration. The microencapsulation serves as a protective barrier to effectively isolate the drug from the external environment, which greatly reduces the risk of degradation of the drug during storage, thus ensuring the high quality of the drug.

Description

DESCRIPTION LU600993

PROCESS FOR PREPARING SUSTAINED-RELEASE ORAL PREPARATIONS

BASED ON MICROENCAPSULATION TECHNOLOGY

TECHNICAL FIELD

This invention relates to the field of pharmaceutical technology, and more specifically to a process for preparing sustained-release oral preparations based on microencapsulation technology.

BACKGROUND TECHNOLOGY

As an advanced drug dosage form, sustained-release oral preparations have the excellent ability to precisely control the release rate of the drug, which can effectively prolong the action time of the drug in the body and significantly reduce the number of drug administrations for the patient. This feature not only optimizes the effect of drug treatment, but also greatly improves the convenience of drug administration for the patient.

Microencapsulation technology is a key means of achieving sustained drug release.

The core principle is to encapsulate the drug in a microcapsule. By carefully controlling the microcapsule material and preparation process, the release characteristics of the microcapsule can be precisely controlled, thereby achieving precise control of the drug release process and achieving the purpose of long-acting sustained release.

Microencapsulation technology is widely used in the pharmaceutical industry.

On the one hand, microcapsules can isolate the drug from adverse external factors;600993 like a fortress, improve the stability of the drug, and effectively reduce the risk of degradation during storage and use. On the other hand, by steadily controlling the release rate of the drug, it can avoid large fluctuations in blood drug concentration and significantly reduce the incidence of drug side effects. The reduced number of administrations of sustained-release oral preparations greatly simplifies the medication process for patients, reduces the possibility of patients missing or forgetting to take medication, significantly improves patient medication compliance, and enables patients to cooperate more actively with treatment, laying a solid foundation for improving the overall treatment effect.

INVENTION CONTENT

The purpose of the present invention is to provide a preparation process for sustained-release oral preparations based on microencapsulation technology to solve the problems set forth in the above background technology.

To achieve the above purpose, the present invention provides the following technical solution: a preparation process for slow-release oral preparations based on microencapsulation technology, comprising the following steps:

S1, drug selection and pretreatment

In the research and development process of slow-release preparations, drugs such as ibuprofen, which are commonly used for antipyretic, analgesic, and anti-inflammatory purposes, and metformin hydrochloride, which is widely used in the treatment of diabetes, are high-quality choices for preparing slow-release preparations because they have suitable pharmacokinetic properties.

After the drugs are selected, they need to be finely pre-processed. Advancgdgooggs crushing technology is used, and professional equipment such as an air jet mill is used to crush drugs such as ibuprofen and metformin hydrochloride. During the crushing process, the powerful impact of the high-pressure airflow is used to gradually refine the drug particles. At the same time, high-precision particle size testing equipment, such as a laser particle size analyzer, is used to monitor the particle size changes of the drug particles in real time and with high accuracy.

S2. Selection and preparation of microencapsulated materials

Polylactic acid was selected as the key material for constructing the microcapsules.

An appropriate amount of polylactic acid was weighed and slowly added to the dichloromethane solvent. During the addition process, the magnetic stirring device was turned on simultaneously, and the stirring speed was set to 300-500 r/min to promote the uniform dispersion of polylactic acid in dichloromethane. As stirring continued, the polylactic acid gradually dissolved. After precise blending, a polylactic acid solution with a mass fraction of 10% was finally formed.

S3. Mixing of the drug with the microencapsulated material

The finely crushed and uniformly sized drug is slowly and evenly sprinkled into the prepared PLA solution. During this process, the stirring device is turned on simultaneously, and the stirring is continued at a low speed of 150-200 r/min to gradually and evenly disperse the drug particles in the PLA solution, thereby forming a stable drug suspension.

The drug suspension is then transferred to an emulsifying device with high-speed stirring function.

The stirring speed is set to 1000 rpm and the stirring time is 10 minutes. Under th&,600993 action of high-speed shearing force, the drug particles in the drug suspension are fully mixed and emulsified with the PLA solution.

S4. Microencapsulation process

The prepared uniform drug emulsion is transported to a professional spray drying device at a stable flow rate with the help of a high-precision peristaltic pump. The spray drying device is equipped with a precise temperature control system. During operation, the inlet temperature of the device is set precisely to 120°C, and the outlet temperature is maintained at 60°C.

The drug emulsion is dispersed into countless tiny mist droplets and sprayed out through a specially designed atomizing nozzle under the action of high-pressure airflow.

Once these droplets are sprayed, they quickly come into contact with the high-temperature hot air flow. Under the rapid heating of the hot air, the solvent in the droplets (such as dichloromethane) evaporates rapidly, and the polylactic acid solidifies, tightly locking the drug particles it contains. As the hot air continues to flow, the droplets dry further, eventually forming uniform-sized, regular-shaped microcapsule particles, which are collected from the outlet of the equipment, completing the efficient preparation process from the drug emulsion to the microcapsule particles.

S5, Post-processing of microcapsules LU600993

After spray drying, the resulting microcapsules are placed in a clean container and washed with an appropriate amount of ethanol as the washing medium. Gentle stirring is used, with the rotational speed controlled at 100-150r/min, to allow the ethanol to fully contact the microcapsules, thereby effectively removing the drugs that were not successfully encapsulated on the surface of the microcapsules as well as any residual polylactic acid.

After the washing process is complete, the filtered microcapsules are transferred to a vacuum drying oven for drying. The parameters of the vacuum drying oven are precisely controlled, with the set temperature being 40°C and the vacuum degree in the oven being maintained at 0.05-0.08MPa. The drying time is set to 24 hours. Under these conditions, the residual ethanol and a small amount of water in the microcapsules can fully volatilize, and finally, microcapsule particles with a dry texture and stable performance are obtained, to prepare for the subsequent formulation forming and quality testing processes;

S6. Screening and grading of microcapsules

A 100-mesh sieve is used to screen the microcapsule particles after vacuum drying.

The microcapsule particles are slowly and evenly poured onto the sieve, and the vibration device is turned on at the same time to vibrate the sieve at a frequency of 100-150 times/minute, so as to cause the microcapsule particles to roll and flow fully on the sieve.

Using professional testing equipment such as a laser particle size analyzer, th&500993 particle size of the screened microcapsules is accurately measured, and the microcapsules are carefully divided into different grades. Microcapsules with a particle size of 50-80 um and a cumulative drug release rate of 10%-20% in simulated gastric juice within 2 hours and a cumulative drug release rate of 70%-80% in simulated intestinal juice within 12 hours are classified as first-grade microcapsules. Microcapsules with a particle size of 80-120 um and corresponding to a drug release rate in simulated gastric and intestinal fluids in another specific range, are classified as secondary microcapsules, and so on, to achieve a scientific classification of microcapsules to meet the needs of different preparations;

S7, preparation of sustained-release oral preparations

After the microcapsule particles are graded, the microcapsule particles are mixed with various excipients according to the formulation ratio. Microcrystalline cellulose is selected as the filler, microcrystalline cellulose as a filler, hydroxypropyl methylcellulose as a binder, and magnesium stearate as a lubricant. During the mixing process, a three-dimensional mixer was used, with a set speed of 20-30 r/min and a mixing time of 15-20 minutes, to thoroughly blend the microcapsule particles with microcrystalline cellulose, hydroxypropyl methylcellulose, and magnesium stearate to form a mixture with a uniform texture and precise distribution of each component.

The resulting uniform mixture is transferred to a high-precision tablet press for tablet pressing. The tablet weight is controlled to 500 mg as required. During the tablet pressing process, key indicators such as the pressure of the tablet press and the weight difference of the tablets are monitored in real time.

The weight difference of the tablets is controlled to within +5% to ensure that th&,500993 weight of each tablet is accurate, the quality is stable, and the production standards are met.

After tablet pressing is complete, hydroxypropyl methylcellulose is used as the coating material. An efficient coating machine is used, with the coating liquid spray rate set at 5-8 mL/min and the coating pan speed at 15-20 r/min. Under suitable temperature (generally 30-35°C) and humidity (relative humidity 40%-50%) conditions, the hydroxypropyl methylcellulose coating solution is sprayed evenly onto the surface of the tablet;

S8, packaging and storage

An automated aluminum-plastic packaging machine is used to accurately place the tablet in the groove of the medicinal aluminum-plastic blister board, cover it with a layer of aluminum foil that fits the blister board, and use a heat sealing process to tightly adhere the aluminum foil to the blister board, ensuring that the tablet is sealed in an independent blister space;

The finished aluminum-plastic packaged tablets need to be stored in a specific environment to maintain their quality and stability. The storage environment is set to be a cool, dry space with the temperature precisely controlled at 25°C. This temperature can both prevent the tablets from degrading due to high temperatures and avoid problems such as the packaging materials becoming brittle due to low temperatures.

Preferably, in the above-mentioned step S1, the particle size of the drug is limited to the range of 5-20 microns to ensure that the size of each drug particle is uniform and consistent.

Uniform drug particles can achieve more thorough and uniform dispersion during,500993 subsequent mixing with the sustained-release material and during the preparation forming process, laying a solid foundation for the sustained and stable release of the drug in the body by the sustained-release preparation and effectively ensuring the quality and efficacy of the sustained-release preparation.

Preferably, in the above-mentioned step S2, a high-precision electronic balance is used during the solution preparation process to ensure that the weighing accuracy of the polylactic acid is +0.001g, and a pipette is used to accurately measure the dichloromethane to ensure the accuracy of the solution concentration, so as to provide reliable quality raw materials for the subsequent smooth development of the microcapsule preparation process.

Preferably, in the above-mentioned step S3, as stirring progresses, a uniform, fine and stable pharmaceutical emulsion gradually forms in the system, in which the pharmaceutical particles are uniformly encapsulated in the tiny droplets formed by the

PLA solution, laying a solid foundation for the subsequent microencapsulation process to achieve effective drug encapsulation and sustained-release properties.

Preferably, in the above-mentioned step S5, the washing time of the microcapsules is generally maintained at 15-20 minutes, and then filtered through a microporous filter membrane. The pore size of the filter membrane is selected according to the particle size of the microcapsules, generally 0.45-0.8um, to ensure that the microcapsules are retained while the washing liquid can be filtered out smoothly. This is repeated 2-3 times to ensure the purity of the microcapsules.

Preferably, in the above-mentioned step S6, under the action of vibration screening, googg3 microcapsule particles with a particle size that does not meet the standard of a 100-mesh screen are effectively separated, and only microcapsule particles with an appropriate particle size are allowed to pass through the screen, thereby initially ensuring that the particle size distribution of the microcapsule particles under the screen is relatively uniform.

Preferably, in the above-mentioned step S7, as the coating solution is sprayed and dried, a uniform, dense coating film is formed on the surface of the tablet, improving the aesthetics and stability of the tablet, while further regulating the drug release rate to meet different clinical medication needs.

Preferably, in the above-mentioned step S8, the storage area is equipped with professional temperature and humidity monitoring equipment to record environmental data in real time, and an abnormal temperature and humidity alarm system is set up.

Once the environmental parameters exceed the set range, an alarm is immediately issued so that the staff can take timely control measures to ensure the suitability of the tablet storage environment.

Compared with the prior art, the present invention provides a preparation process for slow-release oral preparations based on microencapsulation technology, which has the following beneficial effects: 1. The preparation process for slow-release oral preparations based on microencapsulation technology uses microencapsulation technology, which enables the drug to be released slowly and continuously in the body, thereby significantly extending its duration of action and greatly reducing the frequency of administration.

This technology ensures the stability and persistence of the efficacy, therek;600993 improving the overall therapeutic effect. As a protective barrier, the microcapsule effectively isolates the drug from the external environment, greatly reducing the risk of drug degradation during storage and thereby ensuring the high quality of the drug. As a result, when the patient uses it, the drug can exhibit a more reliable and stable therapeutic effect. 2. The preparation process of sustained-release oral preparations based on microencapsulation technology can precisely control the release rate of the drug.

Microencapsulation technology can maintain a stable blood drug concentration, effectively reducing the side effects caused by concentration fluctuations, thereby making the entire treatment process safer and more comfortable. In addition, as a sustained-release preparation, it significantly reduces the number of times patients take medication, greatly simplifies the medication process, and thus reduces the risk of forgetting or missing a dose. This improvement makes it easier for patients to follow medical advice and improves treatment compliance and effectiveness.

Illustration

In order to more clearly illustrate the technical solution of the embodiments of the present invention, the following provides a brief description of the drawings needed for use in the description of the embodiments. Obviously, the drawings described below are only some embodiments of the present invention.

For a person skilled in the art, without having to use creative labor, other drawing$,600993 can also be obtained based on these drawings:

Figure 1 is a flowchart of the preparation method of the present invention.

Specific embodiments

The following will clearly and completely describe the technical solution of the embodiments of the present invention in combination with the appended drawings of the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, not all of them. All other embodiments obtained by a person skilled in the art without creative effort are within the scope of protection of the present invention based on the embodiments of the present invention.

In the present invention, unless otherwise expressly provided and limited, terms such as “installed,” “connected,” “connected,” and “fixed” shall be understood in a broad sense. For example, they may be fixed connections, removable connections, or integral; they may be mechanical connections or electrical connections; they may be directly connected or indirectly connected through intermediate media; they may be the internal connection of two components or the interactive relationship between two components.

For a person skilled in the art, the specific meaning of the above terms in the invention can be understood according to the specific context.

The invention provides the following technical solutions:

Example 1 LU600993

In combination with Figure 1, the preparation process of a sustained-release oral preparation based on microencapsulation technology includes the following steps:

S1, drug selection and pretreatment

In the research and development process of sustained-release preparations, drugs such as ibuprofen, which are commonly used for antipyretic, analgesic, and anti-inflammatory purposes, and metformin hydrochloride, which is widely used in the treatment of diabetes, are excellent choices for preparing sustained-release preparations because they have suitable pharmacokinetic properties.

After the drugs are selected, they need to be finely pre-processed. Advanced crushing technology is used, and professional equipment such as an air jet mill is used to crush drugs such as ibuprofen and metformin hydrochloride. During the crushing process, the powerful impact of the high-pressure airflow is used to gradually refine the drug particles. At the same time, high-precision particle size testing equipment, such as a laser particle size analyzer, is used to monitor the particle size changes of the drug particles in real time and with high accuracy.

S2. Selection and preparation of microencapsulated materials

An appropriate amount of polylactic acid was weighed and slowly added to the dichloromethane solvent. During the addition process, the magnetic stirring device was turned on simultaneously, and the stirring speed was set to 300-500 r/min to promote the uniform dispersion of polylactic acid in dichloromethane.

As stirring continued, the polylactic acid gradually dissolved. After precise blending googg3 a polylactic acid solution with a mass fraction of 10% was finally formed.

S3. Mixing of the drug with the microencapsulated material

The drug suspension is then transferred to an emulsifying device with high-speed stirring function. The stirring speed is set to 1000 rpm and the stirring time is 10 minutes.

Under the action of high-speed shearing force, the drug particles in the drug suspension are fully mixed and emulsified with the PLA solution.

S4. Microencapsulation process

Once these droplets are sprayed, they quickly come into contact with the high-temperature hot air flow.

Under the rapid heating of the hot air, the solvent in the droplets (such a$;500993 dichloromethane) evaporates rapidly, and the polylactic acid solidifies, tightly locking the drug particles it contains. As the hot air continues to flow, the droplets dry further, eventually forming uniform-sized, regular-shaped microcapsule particles, which are collected from the outlet of the equipment, completing the efficient preparation process from the drug emulsion to the microcapsule particles.

S5, Post-processing of microcapsules

After spray drying, the resulting microcapsules are placed in a clean container and washed with an appropriate amount of ethanol as the washing medium. Gentle stirring is used, with the rotational speed controlled at 100-150 r/min, to allow the ethanol to fully contact the microcapsules, thereby effectively removing the drugs that were not successfully encapsulated on the surface of the microcapsules as well as the residual polylactic acid.

After the washing process is complete, the filtered microcapsules are transferred to a vacuum drying oven for drying. The parameters of the vacuum drying oven are precisely controlled, with the temperature set at 40°C and the vacuum degree in the oven maintained at 0.05-0.08MPa. The drying time is set at 24 hours. Under these conditions, the residual ethanol and a small amount of water in the microcapsules can fully volatilize, and finally obtain microcapsule particles with a dry texture and stable performance, ready for subsequent preparation molding and quality testing.

S6. Screening and grading of microcapsules LU600993

The microcapsule particles are slowly and evenly poured onto the sieve, and the vibration device is turned on at the same time to vibrate the sieve at a frequency of 100-150 times/minute, causing the microcapsule particles to roll and flow fully on the sieve.

Using professional testing equipment such as a laser particle size analyzer, the particle size of the screened microcapsules is accurately measured, and the microcapsules are carefully divided into different grades. Microcapsules with a particle size of 50-80 um and a cumulative drug release rate of 10%-20% in simulated gastric juice within 2 hours and a cumulative drug release rate of 70%-80% in simulated intestinal juice within 12 hours are classified as first-grade microcapsules. Microcapsules with a particle size of 80-120 um and corresponding to a drug release rate in simulated gastric and intestinal fluids in another specific range, are classified as secondary microcapsules, and so on, to achieve a scientific classification of microcapsules to meet the needs of different preparations;

S7, preparation of sustained-release oral preparations

After the microcapsule particles are graded, the microcapsule particles are mixed with various excipients according to the formulation ratio. Microcrystalline cellulose is selected as the filler, microcrystalline cellulose as a filler, hydroxypropyl methylcellulose as a binder, and magnesium stearate as a lubricant.

During the mixing process, a three-dimensional mixer was used, with a set speed Pf;600993 20-30 r/min and a mixing time of 15-20 minutes, to thoroughly blend the microcapsule particles with microcrystalline cellulose, hydroxypropyl methylcellulose, and magnesium stearate to form a mixture with a uniform texture and precise distribution of each component.

The resulting homogeneous mixture is transferred to a high-precision tablet press for tablet pressing. The tablet weight is controlled to 500 mg as required. During the tablet pressing process, key indicators such as the pressure of the tablet press and the weight difference of the tablets are monitored in real time. The weight difference of the tablets is controlled to within £5% to ensure that the weight of each tablet is accurate, the quality is stable, and the production standards are met.

After the tablets are pressed, hydroxypropyl methyl cellulose is selected as the coating material, and a high-efficiency coating machine is used the spray rate of the coating solution is set at 5-8mL/min, the speed of the coating pan is 15-20r/min, and the coating solution is evenly sprayed on the surface of the tablet under suitable temperature (generally 30-35°C) and humidity (relative humidity 40%-50%) conditions;

S8, Packaging and storage

An automated aluminum-plastic packaging machine is used to accurately place the tablets in the grooves of the medicinal aluminum-plastic blister board, cover them with a layer of aluminum foil that matches the blister board, and use a heat sealing process to tightly adhere the aluminum foil to the blister board, ensuring that the tablets are sealed in individual blister spaces.

The finished aluminum-plastic packaged tablets need to be stored in a specifi&;600993 environment to maintain their stable quality. The storage environment is set to be a cool, dry space with the temperature precisely controlled at 25°C. This temperature can not only prevent the tablets from degrading due to high temperatures, but also prevent problems such as the packaging materials becoming brittle due to low temperatures.

Example 2

Refer to Figure 1, and on the basis of Example 1, a further preparation process for a sustained-release oral preparation based on microencapsulation technology is obtained, comprising the following steps:

S1. Drug selection and pretreatment

In the research and development process of sustained-release preparations, drugs commonly used for antipyretic, analgesic, and anti-inflammatory purposes, such as ibuprofen, and metformin hydrochloride, which is widely used in the treatment of diabetes, are high-quality choices for preparing sustained-release preparations because they have suitable pharmacokinetic properties.

S2. Selection and preparation of microencapsulated materials LU600993

S3. Mixing of the drug with the microencapsulated material

S4. Microencapsulation process

The prepared uniform drug emulsion is transported to a professional spray drying device at a stable flow rate with the help of a high-precision peristaltic pump. The spray drying device is equipped with a precise temperature control system.

During operation, the inlet temperature of the device is set precisely to 120°C, andıeo0993 the outlet temperature is maintained at 60°C.

S5, Post-processing of microcapsules

After the washing process is complete, the filtered microcapsules are transferred to a vacuum drying oven for drying. The parameters of the vacuum drying oven are precisely controlled, with the set temperature being 40°C and the vacuum degree in the oven maintained at 0.05-0.08MPa. The drying time is set to 24 hours.

Under these conditions, the residual ethanol and a small amount of water in th&500993 microcapsules can fully volatilize, and finally, dry and stable microcapsule particles, ready for subsequent preparation and quality testing;

S6. Microcapsule screening and classification

The microcapsule particles are slowly and evenly poured onto the sieve, while the vibration device is turned on to vibrate the sieve at a frequency of 100-150 times per minute, causing the microcapsule particles to roll and flow fully on the sieve.

S7, preparation of sustained-release oral preparations

The resulting homogeneous mixture is transferred to a high-precision tablet press for tablet pressing. The weight of the tablets is controlled to 500 mg as required. During the tablet pressing process, key indicators such as the pressure of the tablet press and the weight difference of the tablets are monitored in real time. The weight difference of the tablets is controlled to within £5% to ensure that the weight of each tablet is accurate, the quality is stable, and the production standards are met.

After the tablets are pressed, hydroxypropyl methyl cellulose is selected as the coating material. using a high-efficiency coating machine, set the spray rate of the coating solution to 5-8mL/min, the speed of the coating pan to 15-20r/min, and spray the hydroxypropyl methyl cellulose coating solution evenly on the surface of the tablet under suitable temperature (generally 30-35°C) and humidity (relative humidity 40%-50%) conditions;

S8, packaging and storage LU600993

The finished aluminum-plastic packaged tablets need to be stored in a specific environment to maintain their stable quality. The storage environment is set to be a cool, dry space with the temperature precisely controlled at 25°C. This temperature can both prevent the tablets from degrading due to high temperatures and avoid problems such as the packaging materials becoming brittle due to low temperatures.

In the above-mentioned step S1, the particle size of the drug is limited to the range of 5-20 microns to ensure that the size of each drug particle is uniform and consistent.

Uniform drug particles can achieve more thorough and uniform dispersion during the subsequent mixing with the sustained-release material and the formulation forming process, laying a solid foundation for the sustained-release preparation to stably and continuously release the drug in the body, and effectively ensuring the quality and efficacy of the sustained-release preparation.

In the above-mentioned step S2, during the solution preparation process, |3,600993 high-precision electronic balance is used to ensure that the weighing accuracy of the polylactic acid is +0.001g, and a pipette is used to accurately measure the dichloromethane to ensure the accuracy of the solution concentration, so as to provide reliable quality raw materials for the subsequent smooth development of the microcapsule preparation process;

In the above-mentioned step S3, as stirring progresses, a uniform, fine and stable pharmaceutical emulsion gradually forms in the system, in which the pharmaceutical particles are uniformly encapsulated in the tiny droplets formed by the PLA solution, laying a solid foundation for the effective encapsulation and sustained-release performance of the drug in the subsequent microencapsulation process.

In the above-mentioned step S5, the washing time of the microcapsules is generally maintained at 15-20 minutes, and then filtered through a microporous filter membrane.

The pore size of the filter membrane is selected according to the particle size of the microcapsules, generally 0.45-0.8um, to ensure that the microcapsules are retained while the washing liquid can be successfully filtered out. This is repeated 2-3 times to ensure the purity of the microcapsules.

In the above-mentioned step S6, under the action of vibration screening, microcapsule particles with a particle size that does not meet the 100-mesh screen standard are effectively separated, and only microcapsule particles with an appropriate particle size are allowed to pass through the screen, thereby initially ensuring a relatively uniform particle size distribution of the microcapsule particles below the screen.

In the above-mentioned step S7, as the coating solution is sprayed and dried, |3,600993 uniform, dense coating film is formed on the surface of the tablet, improving the appearance and stability of the tablet, while further regulating the drug release rate to meet different clinical medication needs.

In the above-mentioned step S8, the storage area is equipped with professional temperature and humidity monitoring equipment to record environmental data in real time, and an abnormal temperature and humidity alarm system is set up. Once the environmental parameters exceed the set range, an alarm will be issued immediately so that the staff can take timely control measures to ensure the suitability of the tablet storage environment.

It should be noted that in this article, relational terms such as first and second are used only to distinguish one entity or operation from another, and do not necessarily require or imply any such actual relationship or order between these entities or operations. Moreover, the terms “including”, “includes” or any other variation thereof are intended to cover non-exclusive inclusion, so that the process, method, article or device including a series of elements includes not only those elements but also other elements that are not expressly listed or that are also inherent in such process, method, article or device. In the absence of further limitations, elements qualified by the phrase ‘comprising a...” does not exclude the presence of additional identical elements in the process, method, article or device in which the said element is included.

Claims

CLAIMS LU600993

1. The preparation process of sustained-release oral preparations based on microencapsulation technology includes the following steps:

S1. drug selection and pretreatment in the research and development process of sustained-release preparations, drugs such as ibuprofen, which are commonly used for antipyretic, analgesic, and anti-inflammatory purposes, and metformin hydrochloride, which is widely used in the treatment of diabetes, are high-quality choices for the preparation of sustained-release preparations because they have suitable pharmacokinetic properties: after the drugs are selected, they need to be finely pre-processed; advanced crushing technology is used, and professional equipment such as an air jet mill is used to crush drugs such as ibuprofen and metformin hydrochloride; during the crushing process, the powerful impact of the high-pressure airflow is used to gradually refine the drug particles; at the same time, high-precision particle size testing equipment, such as a laser particle size analyzer, is used to monitor the particle size changes of the drug particles in real time and with high accuracy;

S2. selection and preparation of microencapsulated materials polylactic acid was selected as the key material for constructing the microcapsules; an appropriate amount of polylactic acid was weighed and slowly added to the dichloromethane solvent; during the addition process, the magnetic stirring device was turned on simultaneously, and the stirring speed was set to 300-500 r/min to promote the uniform dispersion of polylactic acid in dichloromethane; as stirring continued, the polylactic acid gradually dissolved; after precise blending, a polylactic acid solution with;500993 a mass fraction of 10% was finally formed;

S3. mixing of the drug with the microencapsulated material the finely crushed and uniformly sized drug is slowly and evenly sprinkled into the prepared PLA solution; during this process, the stirring device is turned on simultaneously, and the stirring is continued at a low speed of 150-200 r/min to gradually and evenly disperse the drug particles in the PLA solution, thereby forming a stable drug suspension; the drug suspension is then transferred to an emulsifying device with high-speed stirring function; the stirring speed is set to 1000 rpm and the stirring time is 10 minutes; under the action of high-speed shearing force, the drug particles in the drug suspension are fully mixed and emulsified with the PLA solution;

S4. microencapsulation process the prepared uniform drug emulsion is transported to a professional spray drying device at a stable flow rate with the help of a high-precision peristaltic pump; the spray drying device is equipped with a precise temperature control system; during operation, the inlet temperature of the device is set precisely to 120°C, and the outlet temperature is maintained at 60°C; the drug emulsion is dispersed into countless tiny mist droplets and sprayed out through a specially designed atomizing nozzle under the action of high-pressure airflow; once these droplets are sprayed, they quickly come into contact with the high-temperature hot air flow; under the rapid heating of the hot air, the solvent in the droplets (such as dichloromethane) evaporates rapidly, and the polylactic acid solidifieß 690993 tightly locking the drug particles it contains; as the hot air continues to flow, the droplets dry further, eventually forming uniform-sized, regular-shaped microcapsule particles, which are collected from the outlet of the equipment, completing the efficient preparation process from the drug emulsion to the microcapsule particles; S5, post-processing of microcapsules after spray drying, the resulting microcapsules are placed in a clean container and washed with an appropriate amount of ethanol as the washing medium; gentle stirring is used, with the rotational speed controlled at 100-150 r/min, to allow the ethanol to fully contact the microcapsules, thereby effectively removing the drugs that were not successfully encapsulated on the surface of the microcapsules as well as the residual polylactic acid; after the washing process is complete, the filtered microcapsules are transferred to a vacuum drying oven for drying; the parameters of the vacuum drying oven are precisely controlled, with the temperature set at 40°C and the vacuum degree in the oven maintained at 0.05-0.08MPa; the drying time is set at 24 hours; under these conditions, the residual ethanol and a small amount of water in the microcapsules can fully volatilize, and finally obtain microcapsule particles with a dry texture and stable performance, ready for subsequent preparation molding and quality testing;

S6. screening and grading of microcapsules a 100-mesh sieve is used to screen the microcapsule particles after vacuum drying; the microcapsule particles are slowly and evenly poured onto the sieve, and the vibration device is turned on at the same time to vibrate the sieve at a frequency of 100-130 690993 times/minute, causing the microcapsule particles to roll and flow fully on the sieve;

using professional testing equipment such as a laser particle size analyzer, the particle size of the screened microcapsules is accurately measured, and the microcapsules are carefully divided into different grades; microcapsules with a particle size of 50-80 um and a cumulative drug release rate of 10%-20% in simulated gastric juice within 2 hours and a cumulative drug release rate of 70%-80% in simulated intestinal juice within 12 hours are classified as first-grade microcapsules; microcapsules with a particle size of 80-120 um and corresponding to a drug release rate in simulated gastric and intestinal fluids in another specific range, are classified as secondary microcapsules, and so on, to achieve a scientific classification of microcapsules to meet the needs of different preparations;

S7, preparation of sustained-release oral preparations after the microcapsule particles are graded, the microcapsule particles are mixed with various excipients according to the formulation ratio; microcrystalline cellulose is selected as the filler, microcrystalline cellulose as a filler, hydroxypropyl methylcellulose as a binder, and magnesium stearate as a lubricant; during the mixing process, a three-dimensional mixer was used, with a set speed of 20-30 r/min and a mixing time of 15-20 minutes, to thoroughly blend the microcapsule particles with microcrystalline cellulose, hydroxypropyl methylcellulose, and magnesium stearate to form a mixture with a uniform texture and precise distribution of each component;

the resulting homogeneous mixture is transferred to a high-precision tablet press for tablet pressing; the weight of the tablets is controlled to 500 mg as required; during the tablet pressing process, key indicators such as the pressure of the tablet press and th&,600993 weight difference of the tablets are monitored in real time; the weight difference of the tablets is controlled to within £5% to ensure that the weight of each tablet is accurate, the quality is stable, and the production standards are met;

after the tablets are pressed, hydroxypropyl methyl cellulose is selected as the coating material; using a high-efficiency coating machine, set the spray rate of the coating solution to 5-8mL/min, and the speed of the coating pan to 15-20r/min; under suitable temperature (generally 30-35°C) and humidity (relative humidity 40%-50%) conditions, the hydroxypropyl methyl cellulose coating solution is evenly sprayed on the surface of the tablet;

S8, packaging and storage an automated aluminum-plastic packaging machine is used to accurately place the tablets in the grooves of the medicinal aluminum-plastic blister board, cover them with a layer of aluminum foil that matches the blister board, and use a heat sealing process to tightly adhere the aluminum foil to the blister board, ensuring that the tablets are sealed in individual blister spaces;

the tablets in the finished aluminum-plastic packaging must be stored in a specific environment to maintain their quality and stability; the storage environment is set to be a cool, dry space with the temperature precisely controlled at 25°C; this temperature can both prevent the tablets from degrading due to high temperatures and avoid problems such as the packaging materials becoming brittle due to low temperatures;

2. The preparation process for a sustained-release oral preparation based qn,600993 microencapsulation technology according to claim 1, characterized in that in the above-mentioned step S1, the particle size of the drug is limited to the range of 5-20 microns to ensure that the size of each drug particle is uniform and consistent; uniform drug particles can achieve more complete and uniform dispersion during subsequent mixing with the sustained-release material and during the preparation forming process, laying a solid foundation for the sustained-release preparation to stably and continuously release the drug in the body, and effectively ensuring the quality and efficacy of the sustained-release preparation.

3. According to the preparation process of sustained-release oral preparations based on microencapsulation technology as claimed in claim 1, the process is characterized in that in the above-mentioned step S2, in the process of solution preparation, a high-precision electronic balance is used to ensure that the weighing accuracy of polylactic acid reaches +0.001g, and a pipette is used to accurately measure dichloromethane to ensure the accuracy of the solution concentration, so as to provide reliable raw materials for the subsequent smooth development of the microcapsule preparation process.

4. The preparation process of sustained-release oral preparations based on microencapsulation technology according to claim 1 is characterized in that: in the above-mentioned step S3, as stirring progresses, a uniform, fine and stable drug emulsion gradually forms in the system, wherein the drug particles are uniformly encapsulated in the tiny droplets formed by the PLA solution, laying a solid foundation for the effective encapsulation of the drug and the realization of sustained-release performance in the subsequent microencapsulation process.

5. According to the preparation process of sustained-release oral preparation$;600993 based on microencapsulation technology as claimed in claim 1, the process is characterized in that: in the above-mentioned step S5, the washing time of the microcapsules is generally maintained at 15-20 minutes, and then filtered through a microporous filter membrane, and the pore size of the filter membrane is selected according to the particle size of the microcapsules, generally 0.45-0.8 um, to ensure that the microcapsules are retained while the washing liquid can be successfully filtered out, this is repeated 2-3 times to ensure the purity of the microcapsules.

6. The preparation process of a sustained-release oral preparation based on microencapsulation technology according to claim 1 is characterized in that: in the above-mentioned step S6, under the action of vibration screening, microcapsule particles whose particle size does not meet the standard of a 100-mesh screen are effectively separated, and only microcapsule particles with an appropriate particle size are allowed to pass through the screen, thereby initially ensuring a relatively uniform particle size distribution of the microcapsule particles below the screen.

7. According to the preparation process of sustained-release oral dosage forms based on microencapsulation technology as claimed in claim 1, the process is characterized in that in the above-mentioned step S7, as the coating liquid is sprayed and dried, a uniform and dense coating film is formed on the surface of the tablet, which improves the appearance and stability of the tablet and further regulates the drug release rate to meet different clinical medication needs.

8. According to the preparation process of sustained-release oral preparation$;600993 based on microencapsulation technology as claimed in claim 1, the process is characterized in that in the storage area in step S8 above, professional temperature and humidity monitoring equipment is provided to record environmental data in real time, and an abnormal temperature and humidity alarm system is provided, so that once the environmental parameters exceed the set range, an alarm is issued immediately, so that the staff can take timely control measures to ensure the suitability of the tablet storage environment.