Camptothecin analogue solid dispersion as well as preparation method and application thereof

Abstract

The invention discloses a camptothecin analogue solid dispersion as well as a preparation method and the application thereof. The camptothecin analogue solid dispersion is prepared from a camptothecin analogue (I), a water-soluble carrier and functional auxiliary materials, and can be prepared by any one of a rotary evaporation method, a spray drying method and a hot melt extrusion method; through detection, the camptothecin analogue is converted into an amorphous form from an original crystal form and is dispersed in the solid dispersion, the camptothecin analogue solid dispersion prepared by the invention solves the problem of poor water solubility of the camptothecin analogue, and the bioavailability of the camptothecin analogue is improved;.

Description

technical field

[0001] The invention relates to a solid dispersion of camptothecin analogues and a preparation method and application thereof. Background technique

[0002] 40% of the world's marketed drugs are poorly soluble drugs, and the proportion of poorly soluble candidate drugs in the research and development stage is as high as 90%. Therefore, increasing the solubility and dissolution rate of poorly soluble drugs, and then improving their oral bioavailability has become one of the most active research directions in the field of pharmacy. After oral administration, poorly soluble drugs have a small dissolution rate and a slow dissolution rate in gastrointestinal fluid, and incomplete absorption leads to low bioavailability, which affects the efficacy of the drug.

[0003] FL118 shown in formula (I) is a semi-synthetic compound similar to camptothecin, and its molecular structure is 10,11-methylenedioxycamptothecin, which was discovered by American researchers using S...

Examples

Embodiment 1

[0041] The main raw material of the camptothecin analog solid dispersion of the present embodiment is made up of 10% camptothecin analog, 80% PVPk30 and 10% sodium lauryl sulfate, and its specific preparation process is as follows:

[0042] Mix and dissolve 41mg of camptothecin analogues, 320mg of PVP k30 and 43mg of sodium lauryl sulfate in 30mL of 20% acetone-acetonitrile solution (v / v), fully stir at 50°C for 3h, and rotate the mixture The evaporator removes the solvent at 65°C to obtain a camptothecin analog solid dispersion film, put the film in a vacuum oven at 50°C and dry it overnight, then crush it and pass it through a 80-mesh sieve to obtain a camptothecin analog solid Dispersion powder.

Embodiment 2

[0044] The main raw material of the camptothecin analog solid dispersion of the present embodiment is made up of 5% camptothecin analog, 90% PVPk30, and 5% sodium lauryl sulfate, and its specific preparation process is as follows:

[0045] Mix and dissolve 22mg of camptothecin analogues, 396mg of PVP k30 and 21mg of sodium lauryl sulfate uniformly in 23mL of 20% dichloromethane-acetone solution (v / v), fully stir at 50°C for 3h, and dissolve the mixture The solvent was removed by a rotary evaporator at 50°C to obtain a camptothecin analog solid dispersion film, which was dried overnight in a vacuum oven at 50°C, crushed, and passed through an 80-mesh sieve to obtain a camptothecin analog solid dispersion powder.

Embodiment 3

[0047] The main raw material of the camptothecin analog solid dispersion of the present embodiment is made up of 10% camptothecin analog, 80% PVPk30, and 10% sodium lauryl sulfate, and its specific preparation process is as follows:

[0048] 501mg of camptothecin analogs, 4.021g of PVP k30 and 498mg of sodium lauryl sulfate were uniformly mixed and dissolved in 300mL of 20% acetone-acetonitrile solution (v / v), fully stirred at 50°C for 3h, and the mixture solution was used The spray drying method is used for drying, and the spray drying parameters are set as follows: inlet temperature 70°C, outlet temperature 50°C, atomization pressure 4kg / cm 2 1. The speed of the peristaltic pump is 2mL / min, and the powder is collected to obtain the camptothecin analog solid dispersion powder.

technical field

[0001] The invention relates to a solid dispersion of camptothecin analogues and a preparation method and application thereof. Background technique

[0002] 40% of the world's marketed drugs are poorly soluble drugs, and the proportion of poorly soluble candidate drugs in the research and development stage is as high as 90%. Therefore, increasing the solubility and dissolution rate of poorly soluble drugs, and then improving their oral bioavailability has become one of the most active research directions in the field of pharmacy. After oral administration, poorly soluble drugs have a small dissolution rate and a slow dissolution rate in gastrointestinal fluid, and incomplete absorption leads to low bioavailability, which affects the efficacy of the drug.

[0003] FL118 shown in formula (I) is a semi-synthetic compound similar to camptothecin, and its molecular structure is 10,11-methylenedioxycamptothecin, which was discovered by American researchers using S...

Examples

Embodiment 1

[0041] The main raw material of the camptothecin analog solid dispersion of the present embodiment is made up of 10% camptothecin analog, 80% PVPk30 and 10% sodium lauryl sulfate, and its specific preparation process is as follows:

[0042] Mix and dissolve 41mg of camptothecin analogues, 320mg of PVP k30 and 43mg of sodium lauryl sulfate in 30mL of 20% acetone-acetonitrile solution (v / v), fully stir at 50°C for 3h, and rotate the mixture The evaporator removes the solvent at 65°C to obtain a camptothecin analog solid dispersion film, put the film in a vacuum oven at 50°C and dry it overnight, then crush it and pass it through a 80-mesh sieve to obtain a camptothecin analog solid Dispersion powder.

Embodiment 2

[0044] The main raw material of the camptothecin analog solid dispersion of the present embodiment is made up of 5% camptothecin analog, 90% PVPk30, and 5% sodium lauryl sulfate, and its specific preparation process is as follows:

[0045] Mix and dissolve 22mg of camptothecin analogues, 396mg of PVP k30 and 21mg of sodium lauryl sulfate uniformly in 23mL of 20% dichloromethane-acetone solution (v / v), fully stir at 50°C for 3h, and dissolve the mixture The solvent was removed by a rotary evaporator at 50°C to obtain a camptothecin analog solid dispersion film, which was dried overnight in a vacuum oven at 50°C, crushed, and passed through an 80-mesh sieve to obtain a camptothecin analog solid dispersion powder.

Embodiment 3

[0047] The main raw material of the camptothecin analog solid dispersion of the present embodiment is made up of 10% camptothecin analog, 80% PVPk30, and 10% sodium lauryl sulfate, and its specific preparation process is as follows:

[0048] 501mg of camptothecin analogs, 4.021g of PVP k30 and 498mg of sodium lauryl sulfate were uniformly mixed and dissolved in 300mL of 20% acetone-acetonitrile solution (v / v), fully stirred at 50°C for 3h, and the mixture solution was used The spray drying method is used for drying, and the spray drying parameters are set as follows: inlet temperature 70°C, outlet temperature 50°C, atomization pressure 4kg / cm 2 1. The speed of the peristaltic pump is 2mL / min, and the powder is collected to obtain the camptothecin analog solid dispersion powder.

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