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Preparation of solid dispersion of paclitaxel and its homologues and oral preparations thereof

A technology of solid dispersions and homologues, applied in the field of medicine, can solve problems such as limitations in clinical application, achieve tumor suppression effects, significant effects, and improve bioavailability

Inactive Publication Date: 2015-12-09
SHENYANG PHARMA UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] Docetaxel (also known as docetaxel) is a chemical homologue of paclitaxel, only a small part of the functional group is different, the physical and chemical properties are similar, and some paclitaxel homologues are similar in structure to paclitaxel, and all have the above shortcomings , so that its clinical application is greatly limited, therefore, choosing a new method to improve the solubility and dissolution rate of paclitaxel and its homologues, thereby improving its bioavailability is the direction that pharmaceutical workers are working hard to study

Method used

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  • Preparation of solid dispersion of paclitaxel and its homologues and oral preparations thereof
  • Preparation of solid dispersion of paclitaxel and its homologues and oral preparations thereof
  • Preparation of solid dispersion of paclitaxel and its homologues and oral preparations thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0034] Example 1: Preparation of paclitaxel-HPMCAS-LG solid dispersion microspheres (without micronized silica gel)

[0035]Weigh paclitaxel (0.1, 0.3, 0.8g) and hypromellose acetate succinate (HPMCAS-LG) (1.9g, 1.7g, 1.2g) (Shin-Etsu Chemical Co. 2g) into a 50mL Erlenmeyer flask with a ground mouth, add 3~8mL acetone and 3~6mL dichloromethane, and stir until completely dissolved. A drug-polymer solution is formed under magnetic stirring. Use distilled water containing 0.05%~0.15% surfactant sodium dodecylsulfonate as a poor solvent, take 250mL and place it in a columnar preparation container. Slowly add the above suspension into the poor solvent under the stirring (500~700rpm) of the push-type stirring paddle. Once the suspension is poured into a poor solvent, translucent emulsion droplets are formed, and as dichloromethane and acetone continue to diffuse into the poor solvent, the emulsion droplets gradually solidify into microspheres. After stirring for 20-40min, filter ...

Embodiment 2

[0039] Example 2: Paclitaxel-hypromellose phthalate (HP55) solid dispersion microspheres (without micronized silica gel)

[0040] Weigh paclitaxel (0.1, 0.3, 0.7g) and HP55 (1.9g, 1.7g, 1.3g) (Japan Shin-Etsu Chemical Co., Ltd.) (the total amount of drug and polymer is 2g) in a 50mL conical flask with a ground mouth, Add 3~5mL of acetone and 6~8mL of dichloromethane, stir until completely dissolved, and form a drug-polymer solution under magnetic stirring. Other preparation methods are the same as in Example 1. The overall recovery rate is 60-85%. The obtained preparations are named as F4, F5, and F6, and the drug content in the prescription is about 5%, 15%, and 35%.

[0041] It can be seen from Table 2 that better oral bioavailability can also be obtained by using hypromellose phthalate (HP55) as the solid dispersion carrier. As the proportion of drug content in solid dispersion increases, Tmax decreases, but there is no significant difference between F5 and F6. Depend o...

Embodiment 3

[0044] Embodiment 3: Paclitaxel - Preparation of HPMCAS-LG (or HP55) solid dispersion (without micropowdered silica gel, solvent evaporation method)

[0045] Weigh 2 parts of paclitaxel 100mg, mix them with polymer materials HPMCAS-LG (300mg) and HP55 (300mg) respectively (the total amount of drug and polymer in each prescription is 400mg), and add them to a mixed solvent of 2mL acetone and 2mL dichloromethane After dissolving, evenly spread on the glass plate. Place in an oven at 45°C for 12 hours to evaporate the organic solvent to dryness. The solid dispersion mixture was taken off with a razor blade, and the resulting preparations were respectively F7 and F8, and the drug content in the prescription was 25%. It can be seen from Table 3 that better oral bioavailability can also be obtained by using a simple solvent evaporation method. This shows that the combination of drugs and suitable polymers is one of the key factors to improve the oral bioavailability of drugs.

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Abstract

A solid dispersion and solid dispersion microsphere of paclitaxel or a homologue thereof and a preparation method therefor. By means of preparing a solid dispersion and solid dispersion microsphere to improve the rapid release in vivo and in vitro of paclitaxel or a homologue thereof, and by maintaining a supersaturated drug concentration or, in the case of high molecularity, increasing the apparent solubility of the drug, the bioavailability of the drug is increased. The solid dispersion carrier of paclitaxel or a homologue thereof is either hydroxypropyl methylcellulose acetate succinate or hypromellose phthalate or a mixture thereof or a silica gel-based micropowder mixture. The prepared solid dispersion microsphere has a particle size of between 100 and 600 mum and a yield rate of over 80%; the appropriate drug content therefore is between 5% and 40%.

Description

technical field [0001] The present invention relates to the technical field of medicine, specifically, it selects a type of solid dispersion dispersion carrier, and provides a corresponding preparation method to improve the bioavailability and the The method of efficacy. Background technique [0002] Paclitaxel is a broad-spectrum anticancer drug with definite curative effect, but the drug is extremely insoluble, so the injection prepared by dissolving it in a mixture of surfactant (polyoxyethylene castor oil) and ethanol (1:1) is on the market. The quick onset of the injection is an advantage, but the initial blood concentration is high, which is prone to toxic and side effects, especially paclitaxel injection, which uses a large amount of surfactants, resulting in various adverse reactions, which affect the safety of the drug. Therefore, pharmacists are trying to study oral preparations while reforming injection prescriptions. The oral administration preparations of anti...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K9/14A61K31/337A61K47/38A61P35/00
CPCA61K9/1652A61K31/337A61P35/00
Inventor 崔福德朴洪泽朴洪宇杨亮
Owner SHENYANG PHARMA UNIVERSITY
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