Ketoconazole nanometer suspension freeze-dried powder and preparation method thereof

A technology of ketoconazole nanometer and freeze-dried powder, which is applied in freeze-dried transportation, powder transportation, antifungal agents, etc., and can solve the problems of low dissolution and utilization of ketoconazole dosage forms

Inactive Publication Date: 2011-06-29
HUAZHONG NORMAL UNIV
2 Cites 2 Cited by

AI-Extracted Technical Summary

Problems solved by technology

[0003] The object of the invention provides a kind of ketoconazole...
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Abstract

The invention discloses ketoconazole nanometer suspension freeze-dried powder and a preparation method thereof. The ketoconazole nanometer suspension freeze-dried powder is prepared from the following components in part by mass: 1 part of ketoconazole medicinal powder, 1.5 to 4 parts of surfactant and 0.5 to 2 parts of freeze-dried auxiliary material. The preparation method comprises the following steps of: dissolving ketoconazole in mixed solvent of organic solvent and water-soluble organic solvent, adding water in which the surfactant is dissolved, stirring until the mixture is clarified, adding the freeze-dried auxiliary material, stirring until the mixture is clarified, putting into a refrigerator at the temperature of below 20 DEG C, and freeze drying for over 48 hours to prepare the ketoconazole nanometer suspension freeze-dried powder. In the ketoconazole nanometer suspension freeze-dried powder, ketoconazole medicinal granules are reduced to a nanoscale, so the dissolution rate of the ketoconazole in the water is improved greatly, and the antifungal effect of the ketoconazole is fully played. The freeze-dried powder can be applied to the preparation of freeze-dried powder injection, soft capsules, oral liquid, tablets, gel, emulsifiable paste and other liquid and solid formulations which are used for treating superficial and deep fungal infection.

Application Domain

Organic active ingredientsPowder delivery +3

Technology Topic

SolventChemistry +11

Examples

  • Experimental program(21)

Example Embodiment

[0015] Example 1
[0016] Take 10 L of a mixed solvent with a volume ratio of dichloromethane and acetone of 2:8, add 100 g of the original ketoconazole drug, dissolve and filter with suction to remove a small amount of undissolved particles. Weigh 300 g of sodium dodecyl sulfonate into 5 L of water and stir to dissolve. The ketoconazole solution is added into the water in which the sodium dodecyl sulfonate is dissolved, and the ketoconazole nanosuspension is prepared by stirring until it becomes clear. 150 g of sucrose was added to the suspension, dissolved and then placed in a refrigerator below -20° C. for pre-freezing for 12 hours, and then freeze-dried for more than 48 hours to obtain freeze-dried powder. The freeze-dried powder can be dispersed into a clear liquid within half a minute in water, and the measured average particle size of the dispersion is 290 nm. The lyophilized powder was analyzed by headspace gas chromatography and no residual solvent was detected (the minimum detection limit of dichloromethane was 0.027 ppm, and the minimum detection limit of acetone was 102.3 ppm). And the dissolution rates in the buffer medium with PBS of 1.2, 6.8 and 7.4 were 86.9%, 63.5% and 56.8%, respectively.

Example Embodiment

[0017] Example 2
[0018] Take 10 L of a mixed solvent with a volume ratio of dichloromethane and acetone of 2:8, add 100 g of the original ketoconazole drug, dissolve and filter with suction to remove a small amount of undissolved particles. Weigh 120 g of hexadecyl trimethyl ammonium bromide into 5 L of water and stir to dissolve. The ketoconazole solution is added to the water in which cetyltrimethylammonium bromide is dissolved, and the ketoconazole nanosuspension is prepared by stirring until it becomes clear. 50 g of sucrose was added to the suspension, dissolved and then placed in a refrigerator below -20° C. for pre-freezing for 12 hours, and then freeze-dried for more than 48 hours to obtain freeze-dried powder. The freeze-dried powder can be dispersed into a clear liquid within half a minute in water, and the measured average particle size of the dispersion is 360 nm. The lyophilized powder was analyzed by headspace gas chromatography and no residual solvent was detected (the minimum detection limit of dichloromethane was 0.052 ppm, and the minimum detection limit of acetone was 142.1 ppm). And the dissolution rates in the buffer medium with PBS of 1.2, 6.8 and 7.4 were 90.2%, 71.6% and 52.7%, respectively.

Example Embodiment

[0019] Example 3
[0020] Take a mixed solvent of dichloromethane and acetone with a volume ratio of 2:8, add 100 g of the original ketoconazole drug, dissolve and filter with suction to remove a small amount of undissolved particles. Weigh 100 g of Tween 80 into 5 L of water and stir to dissolve. The solution of ketoconazole is added to the water in which Tween 80 is dissolved, and the ketoconazole nanosuspension is prepared by stirring until it becomes clear. 200 g of sucrose was added to the suspension, dissolved and then placed in a refrigerator below -20° C. for pre-freezing for 12 hours, and then freeze-dried for more than 48 hours to obtain freeze-dried powder. The freeze-dried powder can be dispersed into a clear liquid within half a minute in water, and the measured average particle size of the dispersion is 360 nm. The lyophilized powder was analyzed by headspace gas chromatography and no residual solvent was detected (the minimum detection limit of dichloromethane was 0.032 ppm, and the minimum detection limit of acetone was 124.8 ppm). And the dissolution rates in the buffer medium with PBS of 1.2, 6.8 and 7.4 were 81.6%, 72.3% and 56.9%, respectively.

PUM

PropertyMeasurementUnit
Particle size260.0nm
Particle size300.0nm
Particle size240.0nm

Description & Claims & Application Information

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