A sustained-release fluvoxamine and its preparation method

Abstract

This invention belongs to the technical field of fluvoxamine maleate, specifically relating to a sustained-release fluvoxamine and its preparation method. The sustained-release fluvoxamine comprises the following raw materials: fluvoxamine maleate, a sustained-release coating material, a biodegradable polymer material, and a carrier; the carrier is nanoparticles. The preparation method is as follows: fluvoxamine maleate and the carrier are first mixed evenly in a granulator, then the biodegradable polymer material and binder are added, and granulation is performed to obtain intermediate particles. The sustained-release coating material and the intermediate particles are then placed in a coating machine to complete the coating process, obtaining the sustained-release fluvoxamine maleate. This invention can improve the control of drug release rate and enhance drug stability.

Description

Technical Field

[0001] This invention belongs to the technical field of fluvoxamine maleate, specifically relating to a sustained-release fluvoxamine and its preparation method. Background Technology

[0002] Fluvoxamine maleate is a clinically used medication primarily for treating anxiety, depression, and other mental health disorders. However, traditional fluvoxamine maleate medications typically require multiple daily doses to maintain effective drug concentrations in the body. This leads to patient adherence issues, especially with long-term treatment.

[0003] To address this issue, sustained-release fluvoxamine maleate formulations have been researched and developed, aiming to reduce the frequency of dosing while providing a stable drug release rate, thereby improving patient compliance and enhancing treatment efficacy.

[0004] The challenges in preparing sustained-release fluvoxamine maleate include:

[0005] 1. Release rate control: A major challenge in preparing sustained-release formulations is ensuring that fluvoxamine maleate is released at the desired rate. This requires careful tuning of the carrier material and coating technology to achieve a slow release rather than a burst release.

[0006] 2. Drug stability: Fluvoxamine maleate may degrade during the preparation process or storage, so it is necessary to ensure the stability of the drug to prevent drug failure. Summary of the Invention

[0007] The purpose of this invention is to provide a sustained-release fluvoxamine. This invention can improve the control of drug release rate and enhance drug stability.

[0008] A sustained-release fluvoxamine comprises the following raw materials: fluvoxamine maleate, sustained-release coating material, biodegradable polymer material, and carrier; wherein the carrier is nanoparticles.

[0009] Preferably, the nanoparticles include at least one of silica, chitosan nanoparticles, and polylactic acid nanoparticles.

[0010] Using the above technical solution, this application adds a carrier to the raw materials, enabling a "response" between fluvoxamine maleate and the carrier. Fluvoxamine maleate can be adsorbed onto the carrier, which helps control the drug release rate. This application also adds a sustained-release coating material to the raw materials, giving the finished sustained-release fluvoxamine a coating, essentially stratifying the finished sustained-release fluvoxamine. The dissolution rate of each stratum also helps control the drug release rate. This application adds a biodegradable polymer material to the raw materials, allowing fluvoxamine maleate and the carrier to be retained by the biodegradable polymer material, ensuring that the finished sustained-release fluvoxamine gradually degrades within the biological system, thereby slowly releasing the drug.

[0011] Preferably, the sustained-release coating material includes at least one of hydroxypropyl methylcellulose, polycaprolactone, gelatin, and gelatinic acid.

[0012] Preferably, the biodegradable polymer material includes at least one of polylactic acid-glycolic acid copolymer and polylactic acid.

[0013] Preferably, the sustained-release fluvoxamine comprises the following raw materials in parts by weight: 100 parts of fluvoxamine maleate, 10-50% of the sustained-release coating material of fluvoxamine maleate by weight, 100-300% of the biodegradable polymer material of fluvoxamine maleate by weight, and 8-50% of the carrier of fluvoxamine maleate by weight.

[0014] Preferably, the sustained-release fluvoxamine comprises the following raw materials in parts by weight: 100 parts of fluvoxamine maleate, 25 parts of the sustained-release coating material, 199 parts of the biodegradable polymer material, and 36 parts of the carrier.

[0015] Preferably, the sustained-release fluvoxamine comprises the following raw materials: fluvoxamine maleate, sustained-release coating material, biodegradable polymer material, and carrier; the carrier is nanoparticles; the sustained-release coating material is hydroxypropyl methylcellulose, the biodegradable polymer material is polylactic acid-glycolic acid copolymer, and the carrier is silica.

[0016] The present invention also provides a method for preparing sustained-release fluvoxamine, wherein the fluvoxamine maleate and the carrier are first mixed evenly in a granulator, then biodegradable polymer material and binder are added, granulation is performed to obtain intermediate particles, and the sustained-release coating material and the intermediate particles are placed in a coating machine to complete the coating process to obtain sustained-release fluvoxamine maleate.

[0017] Preferably, the coating temperature is 30–40°C.

[0018] Preferably, the mixing time is 20–60 min.

[0019] The beneficial effects of this invention are:

[0020] First, the formulation of this invention is reasonable and has good compatibility. Specifically, the sustained-release fluvoxamine of this application comprises the following raw materials: fluvoxamine maleate, sustained-release coating material, biodegradable polymer material, and carrier. The addition of a carrier to the raw materials allows fluvoxamine maleate to "respond" to the carrier, enabling fluvoxamine maleate to adsorb onto the carrier, which is beneficial for controlling the drug release rate. The addition of a sustained-release coating material to the raw materials provides a coating for the finished sustained-release fluvoxamine, effectively creating stratified layers. The varying dissolution rates of these layers also help control the drug release rate. The addition of a biodegradable polymer material allows fluvoxamine maleate and the carrier to be retained by the biodegradable polymer material, ensuring that the finished sustained-release fluvoxamine gradually degrades within the biological system, thereby slowly releasing the drug.

[0021] Second, the formulation of this application has high specificity, and the components and weight parts have been further optimized. Through controlled factor experiments, it was found that: (1) Compared with other sustained-release coating materials in this application, ethylene carbonate is not very suitable for the formulation system of this application; (2) Compared with other sustained-release coating materials in this application, the sustained-release coating materials of this application are suitable to be hydroxypropyl methylcellulose, polycaprolactone, gelatin, and gelatinic acid, with polycaprolactone being preferred; the carrier is preferably silica; the biodegradable polymer material is preferably polylactic acid-glycolic acid copolymer; (3) Compared with the weight parts of this application, the sustained-release coating material is preferably 25 parts, the biodegradable polymer material is preferably 199 parts, and the carrier is preferably 36 parts; (4) Compared with the existing commercial products, the sustained-release performance of the finished product of this application is better. The content change of the commercial products is 12% lower than that of this application at the same time. The drug content of the commercial products changes faster and the release rate of the commercial products is faster. Moreover, the stability of the commercial products is inferior to that of this application.

[0022] In summary, this invention can improve the control of drug release rate and enhance drug stability. Detailed Implementation

[0023] The technical solutions of the present invention will be clearly and completely described below with reference to the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative effort are within the scope of protection of the present invention.

[0024] Unless otherwise specified, the reagents used in the examples can be readily obtained from commercial companies or prepared in-house.

[0025] Note: The parts in the formula of this invention are parts by weight.

[0026] Table 1

[0027]

[0028]

[0029] Example 1

[0030] A sustained-release fluvoxamine and its preparation method are as follows:

[0031] Referring to the mass fractions in Table 1, fluvoxamine maleate and the carrier were mixed in a granulator for 30 minutes, then biodegradable polymer material and binder (purified water) were added and granulated to obtain intermediate particles. The sustained-release coating material and intermediate particles were then placed in a coating machine for coating at a temperature of 33°C, so that the sustained-release coating material uniformly coated the intermediate particles to obtain sustained-release fluvoxamine.

[0032] Example 2

[0033] A sustained-release fluvoxamine and its preparation method are as follows:

[0034] Referring to the mass fractions in Table 1, fluvoxamine maleate and the carrier were mixed in a granulator for 35 minutes, then biodegradable polymer material and binder (purified water) were added and granulated to obtain intermediate particles. The sustained-release coating material and intermediate particles were then placed in a coating machine for coating at a temperature of 35°C, so that the sustained-release coating material uniformly coated the intermediate particles to obtain sustained-release fluvoxamine.

[0035] Example 3

[0036] A sustained-release fluvoxamine and its preparation method are as follows:

[0037] Referring to the mass fractions in Table 1, fluvoxamine maleate and the carrier were mixed in a granulator for 40 minutes, then biodegradable polymer material and binder (purified water) were added and granulated to obtain intermediate particles. The sustained-release coating material and the intermediate particles were then placed in a coating machine for coating at a temperature of 38°C, so that the sustained-release coating material uniformly coated the intermediate particles to obtain sustained-release fluvoxamine.

[0038] The sustained-release fluvoxamine maleate from Examples 1 to 3 were tested, and the results are shown in Tables 2 and 3 below.

[0039] Detection:

[0040] A commercially available product (fluvoxamine maleate, Zhuhai Free Trade Zone Lizhu Synthetic Pharmaceutical Co., Ltd.) was selected as control example 1.

[0041] Accelerated test: The sample was placed for 30 days at a temperature of 30℃±2℃ and a relative humidity of 65%±5%, and the color change and the change in drug (fluvoxamine maleate) content were observed. The drug content was set to 100% at the beginning and expressed as a reduction ratio.

[0042] Table 2

[0043]

[0044] Table 3

[0045]

[0046] Results analysis:

[0047] (1) Examples 1-3: When only the weight of polycaprolactone is changed and the other ingredients are selected in the lowest possible weight to minimize the impact, the content change in Example 2 is the slowest and the drug release rate is the slowest. The preferred weight of polycaprolactone is 25 parts.

[0048] (2) Examples 1-3 and Comparative Example 1: Comparative Example 1 started to change color after 30 days, and its stability was inferior to that of this application. The content change of Comparative Example 1 was 12% different from that of this application at the same time, and the drug content changed faster and the release rate was faster.

[0049] Table 4

[0050]

[0051]

[0052] Example 4

[0053] A sustained-release fluvoxamine and its preparation method are as follows:

[0054] Referring to the mass fractions in Table 4, fluvoxamine maleate and the carrier were mixed in a granulator for 30 minutes, then biodegradable polymer material and binder (purified water) were added and granulated to obtain intermediate particles. The sustained-release coating material and intermediate particles were then placed in a coating machine for coating at a temperature of 32°C, so that the sustained-release coating material uniformly coated the intermediate particles to obtain sustained-release fluvoxamine.

[0055] Example 5

[0056] A sustained-release fluvoxamine and its preparation method are as follows:

[0057] Referring to the mass fractions in Table 4, fluvoxamine maleate and the carrier were mixed in a granulator for 35 minutes, then biodegradable polymer material and binder (purified water) were added and granulated to obtain intermediate particles. The sustained-release coating material and intermediate particles were then placed in a coating machine for coating at a temperature of 35°C, so that the sustained-release coating material uniformly coated the intermediate particles to obtain sustained-release fluvoxamine.

[0058] Example 6

[0059] A sustained-release fluvoxamine and its preparation method are as follows:

[0060] Referring to the mass fractions in Table 4, fluvoxamine maleate and the carrier were mixed in a granulator for 40 minutes, then biodegradable polymer material and binder (purified water) were added and granulated to obtain intermediate particles. The sustained-release coating material and intermediate particles were then placed in a coating machine for coating at a temperature of 38°C, so that the sustained-release coating material uniformly coated the intermediate particles to obtain sustained-release fluvoxamine.

[0061] Detection: The detection method is the same as that in Examples 1 to 3.

[0062] Table 5

[0063]

[0064] Table 6

[0065]

[0066] Results analysis:

[0067] (1) Examples 4 to 6: When only the weight of polylactic acid-glycolic acid copolymer is changed and the other ingredients are selected in the lowest possible weight to minimize the impact, the content change in Example 5 is the slowest and the drug release rate is the slowest. The preferred weight of polylactic acid-glycolic acid copolymer is 199 parts.

[0068] (2) Examples 4-6 and Comparative Example 1: Comparative Example 1 started to change color after 30 days, and its stability was inferior to that of this application. The content change of Comparative Example 1 was 12.4% different from that of this application at the same time, and the drug content changed faster and the release rate was faster.

[0069] Table 7

[0070]

[0071]

[0072] Example 7

[0073] A sustained-release fluvoxamine and its preparation method are as follows:

[0074] Referring to the mass fractions in Table 7, fluvoxamine maleate and the carrier were mixed in a granulator for 30 minutes, then biodegradable polymer material and binder (purified water) were added and granulated to obtain intermediate particles. The sustained-release coating material and intermediate particles were then placed in a coating machine for coating at a temperature of 32°C, so that the sustained-release coating material uniformly coated the intermediate particles to obtain sustained-release fluvoxamine.

[0075] Example 8

[0076] A sustained-release fluvoxamine and its preparation method are as follows:

[0077] Referring to the mass fractions in Table 7, fluvoxamine maleate and the carrier were mixed in a granulator for 35 minutes, then biodegradable polymer material and binder (purified water) were added and granulated to obtain intermediate particles. The sustained-release coating material and intermediate particles were then placed in a coating machine for coating at a temperature of 35°C, so that the sustained-release coating material uniformly coated the intermediate particles to obtain sustained-release fluvoxamine.

[0078] Example 9

[0079] A sustained-release fluvoxamine and its preparation method are as follows:

[0080] Referring to the mass fractions in Table 7, fluvoxamine maleate and the carrier were mixed in a granulator for 40 minutes, then biodegradable polymer material and binder (purified water) were added and granulated to obtain intermediate particles. The sustained-release coating material and intermediate particles were then placed in a coating machine for coating at a temperature of 38°C, so that the sustained-release coating material uniformly coated the intermediate particles to obtain sustained-release fluvoxamine.

[0081] Detection: The detection method is the same as that in Examples 1 to 3.

[0082] Table 8

[0083]

[0084] Table 9

[0085]

[0086] Results analysis:

[0087] (1) Examples 7-9: When only the weight of silica is changed and the other ingredients are selected in the lowest possible weight to minimize the impact, the content change in Example 8 is the slowest and the drug release rate is the slowest. The preferred weight of silica is 36 parts.

[0088] (2) Examples 7-9 and Comparative Example 1: Comparative Example 1 started to change color after 30 days, and its stability was inferior to that of this application. The content change of Comparative Example 1 was 12.2% different from that of this application at the same time, and the drug content changed faster and the release rate was faster.

[0089] Table 10

[0090]

[0091]

[0092] Example 10

[0093] A sustained-release fluvoxamine and its preparation method are as follows:

[0094] Referring to the mass fractions in Table 10, fluvoxamine maleate and the carrier were mixed in a granulator for 30 minutes, then biodegradable polymer material and binder (purified water) were added and granulated to obtain intermediate particles. The sustained-release coating material and the intermediate particles were then placed in a coating machine for coating at a temperature of 32°C, so that the sustained-release coating material uniformly coated the intermediate particles to obtain released fluvoxamine maleate.

[0095] The preparation methods of Examples 11-13 and Comparative Example 2 are the same as those of Example 10, but the formulations are different, as shown in the table.

[0096] Detection: The detection method is the same as that in Examples 1 to 3.

[0097] Table 11

[0098]

[0099]

[0100] Table 12

[0101]

[0102] Results analysis:

[0103] (1) Examples 10-13: When only the composition of the sustained-release coating material is changed, the optimal weight part is selected as 25 parts, and the other ingredients are selected as the minimum weight part to minimize the impact, the content change in Example 11 is the slowest and the drug release rate is the slowest. The sustained-release coating material of this application is preferably polycaprolactone.

[0104] (2) Examples 10-13 and Comparative Examples 1 and 2: Comparative Example 1 began to change color after 30 days, and its stability was inferior to that of this application. The content change of Comparative Example 1 was 12% different from that of this application at the same time, indicating a faster rate of drug content change and release. Comparative Example 2 showed the fastest change, although it was still within -20%. However, compared with other sustained-release coating materials of this application, ethylene carbonate was not very suitable for the formulation system of this application. Suitable sustained-release coating materials for this application include hydroxypropyl methylcellulose, polycaprolactone, gelatin, and gelatinous acid, with polycaprolactone being preferred.

[0105] Table 13

[0106]

[0107] Example 14

[0108] A sustained-release fluvoxamine and its preparation method are as follows:

[0109] Referring to the mass fractions in Table 13, fluvoxamine maleate and the carrier were mixed in a granulator for 30 minutes, then biodegradable polymer material and binder (purified water) were added and granulated to obtain intermediate particles. The sustained-release coating material and intermediate particles were then placed in a coating machine for coating at a temperature of 32°C, so that the sustained-release coating material uniformly coated the intermediate particles to obtain released fluvoxamine maleate.

[0110] The preparation method of Example 15 is the same as that of Example 14, but the formula is different, as shown in Table 13.

[0111] Detection: The detection method is the same as that in Examples 1 to 3.

[0112] Table 14

[0113]

[0114] Table 15

[0115]

[0116] Results analysis:

[0117] (1) Examples 14-15: When only the components of the biodegradable polymer material are changed, the optimal weight part is selected as 199 parts, and the other ingredients are selected as the minimum weight part to minimize the impact, the content change in Example 14 is the slowest and the drug release rate is the slowest. The biodegradable polymer material of this application is preferably polylactic acid-glycolic acid copolymer.

[0118] (2) Examples 14-15 and Comparative Example 1: Comparative Example 1 started to change color after 30 days, and its stability was inferior to that of this application. The content change of Comparative Example 1 was 12.4% different from that of this application at the same time, and the drug content changed faster and the release rate was faster.

[0119] Table 16

[0120]

[0121] Example 16

[0122] A sustained-release fluvoxamine and its preparation method are as follows:

[0123] Referring to the mass fractions in Table 16, fluvoxamine maleate and the carrier were mixed in a granulator for 30 minutes, then biodegradable polymer material and binder (purified water) were added and granulated to obtain intermediate particles. The sustained-release coating material and the intermediate particles were then placed in a coating machine for coating at a temperature of 32°C, so that the sustained-release coating material uniformly coated the intermediate particles to obtain released fluvoxamine maleate.

[0124] The preparation methods for Examples 17 and 18 are the same as those for Example 16, but the formulations are different, as shown in Table 16.

[0125] Detection: The detection method is the same as that in Examples 1 to 3.

[0126] Table 17

[0127]

[0128] Table 18

[0129]

[0130] Results analysis:

[0131] (1) Examples 16-18: When only the components of the carrier are changed, the optimal weight part is selected as 36 parts, and the other ingredients are selected as the minimum weight part to minimize the impact, the content change in Example 16 is the slowest and the drug release rate is the slowest. The carrier of this application is preferably silica.

[0132] (2) Examples 16-18 and Comparative Example 1: Comparative Example 1 started to change color after 30 days, and its stability was inferior to that of this application. The content change of Comparative Example 1 was 11.6% different from that of this application at the same time, and the drug content changed faster and the release rate was faster.

[0133] In summary, the sustained-release performance and stability of the finished product of this application are superior to those of commercially available products in the prior art. Further optimization of the preparation conditions yields:

[0134] (1) The optimal weight parts are 25 parts for the sustained-release coating material, 199 parts for the biodegradable polymer material, and 36 parts for the carrier.

[0135] (2) The composition is optimal. Compared with other sustained-release coating materials in this application, ethylene carbonate is not very suitable for the formulation system of this application. The sustained-release coating materials of this application are suitable to be hydroxypropyl methylcellulose, polycaprolactone, gelatin, gelatinic acid, with polycaprolactone being preferred; the carrier is preferably silica; and the biodegradable polymer material is preferably polylactic acid-glycolic acid copolymer.

[0136] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art can still modify the technical solutions described in the foregoing embodiments or make equivalent substitutions for some of the technical features. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A sustained-release fluvoxamine, characterized in that, The sustained-release fluvoxamine comprises the following raw materials: fluvoxamine maleate, sustained-release coating material, biodegradable polymer material, and carrier; the carrier is nanoparticles. The nanoparticles include at least one of silica, chitosan nanoparticles, and polylactic acid nanoparticles; The sustained-release coating material includes at least one of hydroxypropyl methylcellulose, polycaprolactone, gelatin, and gelatinic acid. The biodegradable polymer material includes at least one of polylactic acid-glycolic acid copolymer and polylactic acid.

2. The sustained-release fluvoxamine according to claim 1, characterized in that, The sustained-release fluvoxamine comprises the following raw materials in parts by weight: 100 parts of fluvoxamine maleate, 10-50% of the sustained-release coating material of fluvoxamine maleate by weight, 100-300% of the biodegradable polymer material of fluvoxamine maleate by weight, and 8-50% of the carrier of fluvoxamine maleate by weight.

3. The sustained-release fluvoxamine according to claim 1, characterized in that, The sustained-release fluvoxamine comprises the following raw materials in parts by weight: 100 parts of fluvoxamine maleate, 25 parts of the sustained-release coating material, 199 parts of the biodegradable polymer material, and 36 parts of the carrier.

4. The sustained-release fluvoxamine according to claim 1, characterized in that, The sustained-release fluvoxamine comprises the following raw materials: fluvoxamine maleate, sustained-release coating material, biodegradable polymer material, and carrier; the carrier is nanoparticles; the sustained-release coating material is hydroxypropyl methylcellulose, the biodegradable polymer material is polylactic acid-glycolic acid copolymer, and the carrier is silica.

5. A method for preparing sustained-release fluvoxamine according to any one of claims 1 to 4, characterized in that, The fluvoxamine maleate and the carrier are first mixed evenly in a granulator, then biodegradable polymer material and binder are added, and granulation is performed to obtain intermediate particles. The sustained-release coating material and the intermediate particles are then placed in a coating machine to complete the coating process, thereby obtaining sustained-release fluvoxamine maleate.

6. The method for preparing sustained-release fluvoxamine according to claim 1, characterized in that, The coating temperature is 30~40℃.

7. The method for preparing sustained-release fluvoxamine according to claim 1, characterized in that, Mixing time is 20-60 minutes.

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