Hydroxychloroquine sulfate sustained release microsphere for articular cavity injection and preparation method thereof

Abstract

The invention discloses a hydroxychloroquine sulfate sustained-release microsphere for articular cavity injection and a preparation method thereof. The preparation method comprises the following steps: dissolving a surfactant in an organic solvent to form an oil phase; adding hydroxychloroquine sulfate and gelatin into water to obtain a water phase; dropwise adding the water phase into the oil phase, stirring and emulsifying to form a W / O type emulsion; transferring the W / O emulsion into an ice bath, and adding a curing agent for cross-linking curing; and then adding isopropanol for dehydration, suction filtration, washing and drying to obtain the hydroxychloroquine sulfate sustained-release microspheres for articular cavity injection. The prepared hydroxychloroquine microspheres can stably and continuously release drugs for more than 48 hours, a sustained-release preparation is obtained, the administration frequency can be reduced, the total dosage can be reduced, the compliance of patients can be improved, and the clinical application potential is good.

Description

technical field

[0001] The invention belongs to the technical field of pharmaceutical preparations, and in particular relates to a hydroxychloroquine sulfate sustained-release microsphere for joint cavity injection and a preparation method thereof. Background technique

[0002] Hydroxychloroquine sulfate (HCQ) is a 4-aminoquinoline antimalarial drug, and the latest version of the drug is currently included in the main foreign pharmacopoeia of USP-NF2021 (Issue 2) and EP10.4. Initially used for malaria, its role in the treatment of skin and connective tissue diseases was recognized and widely used. It is mainly used for the prevention and treatment of malaria, rheumatoid arthritis and lupus erythematosus.

[0003] Rheumatoid arthritis (RA) is a common chronic, systemic autoimmune disease. The cause of the disease is not yet clear. It is mainly manifested as chronic synovitis, which is cartilage destruction. Patients often have persistent joint pain and swelling. and other c...

Examples

Embodiment 1

[0038] Preparation of HCQ Microspheres

[0039] Dissolve 200mg HCQ in 2ml gelatin solution (gelatin solution is prepared by the following method: weigh 0.6g gelatin and put it into a 50ml beaker and add 6ml water) to obtain an aqueous phase, which will be dropped into the oil phase (weigh 1g of splatter). 80, put into a 50ml beaker and add 30ml of liquid paraffin), control the temperature at 55°C, stir for 20min to form a W / O type emulsion, transfer to an ice bath for 5min and add 5ml of glutaraldehyde solution, stir for 1 hour to solidify, Then add 30ml of isopropanol for dehydration for 30min, then carry out suction filtration, rinse with isopropanol, and dry at room temperature to obtain HCQ microsphere powder.

[0040] Microsphere shape:

[0041] Take the microspheres prepared in Example 1, and measure the shape of the microspheres with a scanning electron microscope, see figure 1 .

[0042] Depend on figure 1 It can be seen that the shape of the HCQ microspheres prepa...

Embodiment 2

[0044] Choice of emulsification time

[0045] The preparation methods of the water phase and the oil phase are the same as those in Example 1.

[0046] The water phase was dropped into the oil phase, the temperature was controlled at 55°C, and the mixture was stirred for 10 min, 20 min, and 30 min respectively to form a W / O type emulsion. After being transferred to an ice bath for 5 min, the glutaraldehyde solution was added. The subsequent operations were the same as those in Example 1. The effects of different curing agent addition times on the encapsulation efficiency (EE) and drug loading (DL) were investigated, and the results are shown in Table 1. It can be seen from Table 1 that 20min was selected as the appropriate emulsification time.

[0047] Table 1. Effects of emulsification time on EE and DL ( n=3).

[0048]

Embodiment 3

[0050] The choice of curing agent adding time

[0051] The preparation methods of the water phase and the oil phase are the same as those in Example 1.

[0052]The water phase was dropped into the oil phase, the temperature was controlled at 55°C, and stirred for 20 min to form a W / O type emulsion, which was added immediately after transferring to the ice bath, 5 min after transferring to the ice bath, and 10 min after transferring to the ice bath. Then, 5 mL of glutaraldehyde solution was added, and the subsequent operations were the same as those in Example 1. The effects of different addition times on the encapsulation efficiency and drug loading were investigated, and the results are shown in Table 2. It can be seen from Table 2 that the time for adding the curing agent is selected as the appropriate time for adding the curing agent after 5 minutes after the ice bath.

[0053] Table 2. Effect of curing agent addition time on EE and DL ( n=3)

[0054]

technical field

[0001] The invention belongs to the technical field of pharmaceutical preparations, and in particular relates to a hydroxychloroquine sulfate sustained-release microsphere for joint cavity injection and a preparation method thereof. Background technique

[0002] Hydroxychloroquine sulfate (HCQ) is a 4-aminoquinoline antimalarial drug, and the latest version of the drug is currently included in the main foreign pharmacopoeia of USP-NF2021 (Issue 2) and EP10.4. Initially used for malaria, its role in the treatment of skin and connective tissue diseases was recognized and widely used. It is mainly used for the prevention and treatment of malaria, rheumatoid arthritis and lupus erythematosus.

[0003] Rheumatoid arthritis (RA) is a common chronic, systemic autoimmune disease. The cause of the disease is not yet clear. It is mainly manifested as chronic synovitis, which is cartilage destruction. Patients often have persistent joint pain and swelling. and other c...

Examples

Embodiment 1

[0038] Preparation of HCQ Microspheres

[0039] Dissolve 200mg HCQ in 2ml gelatin solution (gelatin solution is prepared by the following method: weigh 0.6g gelatin and put it into a 50ml beaker and add 6ml water) to obtain an aqueous phase, which will be dropped into the oil phase (weigh 1g of splatter). 80, put into a 50ml beaker and add 30ml of liquid paraffin), control the temperature at 55°C, stir for 20min to form a W / O type emulsion, transfer to an ice bath for 5min and add 5ml of glutaraldehyde solution, stir for 1 hour to solidify, Then add 30ml of isopropanol for dehydration for 30min, then carry out suction filtration, rinse with isopropanol, and dry at room temperature to obtain HCQ microsphere powder.

[0040] Microsphere shape:

[0041] Take the microspheres prepared in Example 1, and measure the shape of the microspheres with a scanning electron microscope, see figure 1 .

[0042] Depend on figure 1 It can be seen that the shape of the HCQ microspheres prepa...

Embodiment 2

[0044] Choice of emulsification time

[0045] The preparation methods of the water phase and the oil phase are the same as those in Example 1.

[0046] The water phase was dropped into the oil phase, the temperature was controlled at 55°C, and the mixture was stirred for 10 min, 20 min, and 30 min respectively to form a W / O type emulsion. After being transferred to an ice bath for 5 min, the glutaraldehyde solution was added. The subsequent operations were the same as those in Example 1. The effects of different curing agent addition times on the encapsulation efficiency (EE) and drug loading (DL) were investigated, and the results are shown in Table 1. It can be seen from Table 1 that 20min was selected as the appropriate emulsification time.

[0047] Table 1. Effects of emulsification time on EE and DL ( n=3).

[0048]

Embodiment 3

[0050] The choice of curing agent adding time

[0051] The preparation methods of the water phase and the oil phase are the same as those in Example 1.

[0052]The water phase was dropped into the oil phase, the temperature was controlled at 55°C, and stirred for 20 min to form a W / O type emulsion, which was added immediately after transferring to the ice bath, 5 min after transferring to the ice bath, and 10 min after transferring to the ice bath. Then, 5 mL of glutaraldehyde solution was added, and the subsequent operations were the same as those in Example 1. The effects of different addition times on the encapsulation efficiency and drug loading were investigated, and the results are shown in Table 2. It can be seen from Table 2 that the time for adding the curing agent is selected as the appropriate time for adding the curing agent after 5 minutes after the ice bath.

[0053] Table 2. Effect of curing agent addition time on EE and DL ( n=3)

[0054]

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