Voriconazole freeze-dried powder injection for injection and preparation method thereof

Abstract

Belonging to the technical field of drug preparation, the invention relates to a voriconazole freeze-dried powder injection for injection and a preparation method thereof. The invention provides a pharmaceutical preparation that treats invasive fungal infections and has good solubility and high stability for clinical practice. According to a prescription, the voriconazole freeze-dried powder injection for injection provided in the invention is composed of voriconazole, hydroxypropyl-beta-cyclodextrin, mannitol, hydrochloric acid, sodium hydroxide, and water for injection. The preparation process includes: subjecting an aqueous solution of hydroxypropyl-beta-cyclodextrin and an acid solution of voriconazole to clathration, adding mannitol, then conducting stirring dissolving, using a sodium hydroxide solution to adjust the pH value, carrying out activated carbon adsorption, decarbonization, fine filtration by a microfiltration membrane and semi-finished product inspection, if the semi-finished product is qualified, performing subpackaging, freeze-drying, and conducting complete inspection. The cruxes of the preparation method are proportioning of voriconazole and hydroxypropyl-beta-cyclodextrin in the prescription, control of clathration temperature and time, charging sequence and other technical parameters. At the same time, the invention also provides a method for determination of the inclusion encapsulation efficiency.

Description

technical field

[0001] The invention relates to voriconazole freeze-dried powder for injection and a preparation method thereof, and relates to a method for treating invasive aspergillosis, severe invasive infection caused by fluconazole-resistant candida and fungi caused by actinomycetes and fusarium A pharmaceutical preparation for severe infection and a preparation method thereof belong to the technical field of pharmaceutical preparation. Background technique

[0002] In recent years, with the wide application of high-efficiency broad-spectrum antibiotics, immunosuppressants, and anti-cancer drugs, the in-depth development of organ transplantation, catheter technology, and other interventional treatments in surgery, especially the emergence of AIDS, the disease caused by opportunistic fungi Systemic fungal diseases are increasing day by day, new pathogenic bacteria appear constantly, and the condition is becoming more and more serious. Mainly include candidiasis, asperg...

Examples

Embodiment 1

[0058] Embodiment 1 (specification 50mg)

[0059] The weight of each component in the prescription of preparing 1000 voriconazole freeze-dried powder injections for injection is as follows:

[0060] Voriconazole 50g Hydroxypropyl-β-cyclodextrin 400g

[0061] Mannitol 200g 2M hydrochloric acid 250ml

[0062] 2M NaOH to adjust the pH to 5.5 and water for injection to 5L

[0063] The preparation process is as follows:

[0064] Add 400g of hydroxypropyl-β-cyclodextrin to water for injection of 30% of the prescription amount, stir to completely dissolve the hydroxypropyl-β-cyclodextrin; accurately weigh 50g of voriconazole, dissolve it with 250mL of 2M hydrochloric acid, and control Warm at 40°C, add it into the dissolved hydroxypropyl-β-cyclodextrin aqueous solution, and stir while adding; continue to stir for 30 minutes to make voriconazole inclusion as complete as possible; accurately weigh 200g of mannitol, add the above-mentioned package Stir to dissolve the mixed solution; ...

Embodiment 2

[0065] Embodiment 2 (specification 50mg)

[0066] The weight of each component in the prescription of preparing 1000 voriconazole freeze-dried powder injections for injection is as follows:

[0067] Voriconazole 50g Hydroxypropyl-β-cyclodextrin 500g

[0068] Mannitol 200g 2M hydrochloric acid 250ml

[0069] 2M NaOH to adjust the pH to 5.5 and water for injection to 5L

[0070] The preparation process is as follows:

[0071] Add 500g of hydroxypropyl-β-cyclodextrin to water for injection with 40% of the prescription amount, stir to completely dissolve the hydroxypropyl-β-cyclodextrin; accurately weigh 50g of voriconazole, dissolve it with 250mL of 2M hydrochloric acid, and control Warm at 50°C, add it into the dissolved hydroxypropyl-β-cyclodextrin aqueous solution, and stir while adding; continue to stir for 20 minutes to make voriconazole inclusion as complete as possible; accurately weigh 200g of mannitol, add the above-mentioned package Stir to dissolve the mixed soluti...

Embodiment 3

[0072] Embodiment 3 (specification 50mg)

[0073] The weight of each component in the prescription of preparing 1000 voriconazole freeze-dried powder injections for injection is as follows:

[0074] Voriconazole 50g Hydroxypropyl-β-cyclodextrin 600g

[0075] Mannitol 200g 2M hydrochloric acid 250ml

[0076] 2M NaOH to adjust the pH to 5.5 and water for injection to 5L

[0077] The preparation process is as follows:

[0078] Add 600g of hydroxypropyl-β-cyclodextrin to water for injection with 50% of the prescription amount, stir to completely dissolve the hydroxypropyl-β-cyclodextrin; accurately weigh 50g of voriconazole, dissolve it with 250mL of 2M hydrochloric acid, and control Warm at 40°C, add it to the dissolved hydroxypropyl-β-cyclodextrin aqueous solution, and stir while adding; continue to stir for 40 minutes to make voriconazole inclusion as complete as possible; accurately weigh 200g of mannitol, add the above-mentioned package Stir to dissolve the mixed solution...

technical field

[0001] The invention relates to voriconazole freeze-dried powder for injection and a preparation method thereof, and relates to a method for treating invasive aspergillosis, severe invasive infection caused by fluconazole-resistant candida and fungi caused by actinomycetes and fusarium A pharmaceutical preparation for severe infection and a preparation method thereof belong to the technical field of pharmaceutical preparation. Background technique

[0002] In recent years, with the wide application of high-efficiency broad-spectrum antibiotics, immunosuppressants, and anti-cancer drugs, the in-depth development of organ transplantation, catheter technology, and other interventional treatments in surgery, especially the emergence of AIDS, the disease caused by opportunistic fungi Systemic fungal diseases are increasing day by day, new pathogenic bacteria appear constantly, and the condition is becoming more and more serious. Mainly include candidiasis, asperg...

Examples

Embodiment 1

[0058] Embodiment 1 (specification 50mg)

[0059] The weight of each component in the prescription of preparing 1000 voriconazole freeze-dried powder injections for injection is as follows:

[0060] Voriconazole 50g Hydroxypropyl-β-cyclodextrin 400g

[0061] Mannitol 200g 2M hydrochloric acid 250ml

[0062] 2M NaOH to adjust the pH to 5.5 and water for injection to 5L

[0063] The preparation process is as follows:

[0064] Add 400g of hydroxypropyl-β-cyclodextrin to water for injection of 30% of the prescription amount, stir to completely dissolve the hydroxypropyl-β-cyclodextrin; accurately weigh 50g of voriconazole, dissolve it with 250mL of 2M hydrochloric acid, and control Warm at 40°C, add it into the dissolved hydroxypropyl-β-cyclodextrin aqueous solution, and stir while adding; continue to stir for 30 minutes to make voriconazole inclusion as complete as possible; accurately weigh 200g of mannitol, add the above-mentioned package Stir to dissolve the mixed solution; ...

Embodiment 2

[0065] Embodiment 2 (specification 50mg)

[0066] The weight of each component in the prescription of preparing 1000 voriconazole freeze-dried powder injections for injection is as follows:

[0067] Voriconazole 50g Hydroxypropyl-β-cyclodextrin 500g

[0068] Mannitol 200g 2M hydrochloric acid 250ml

[0069] 2M NaOH to adjust the pH to 5.5 and water for injection to 5L

[0070] The preparation process is as follows:

[0071] Add 500g of hydroxypropyl-β-cyclodextrin to water for injection with 40% of the prescription amount, stir to completely dissolve the hydroxypropyl-β-cyclodextrin; accurately weigh 50g of voriconazole, dissolve it with 250mL of 2M hydrochloric acid, and control Warm at 50°C, add it into the dissolved hydroxypropyl-β-cyclodextrin aqueous solution, and stir while adding; continue to stir for 20 minutes to make voriconazole inclusion as complete as possible; accurately weigh 200g of mannitol, add the above-mentioned package Stir to dissolve the mixed soluti...

Embodiment 3

[0072] Embodiment 3 (specification 50mg)

[0073] The weight of each component in the prescription of preparing 1000 voriconazole freeze-dried powder injections for injection is as follows:

[0074] Voriconazole 50g Hydroxypropyl-β-cyclodextrin 600g

[0075] Mannitol 200g 2M hydrochloric acid 250ml

[0076] 2M NaOH to adjust the pH to 5.5 and water for injection to 5L

[0077] The preparation process is as follows:

[0078] Add 600g of hydroxypropyl-β-cyclodextrin to water for injection with 50% of the prescription amount, stir to completely dissolve the hydroxypropyl-β-cyclodextrin; accurately weigh 50g of voriconazole, dissolve it with 250mL of 2M hydrochloric acid, and control Warm at 40°C, add it to the dissolved hydroxypropyl-β-cyclodextrin aqueous solution, and stir while adding; continue to stir for 40 minutes to make voriconazole inclusion as complete as possible; accurately weigh 200g of mannitol, add the above-mentioned package Stir to dissolve the mixed solution...

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