Gemcitabine hydrochloride lyophilized composition and preparation method thereof

Abstract

The invention relates to a gemcitabine hydrochloride lyophilized composition and a preparation method thereof, and aims to solve the technical problems of poor stability and long production cycle in the current gemcitabine hydrochloride lyophilized preparation. The gemcitabine hydrochloride lyophilized composition comprises the following components: gemcitabine hydrochloride, cyclodextrin or cyclodextrin derivative, lyophilized excipient and pH regulator, wherein the weight proportion of the components is 1:0.2-0.55:0.2-0.7:0.01-0.1. The gemcitabine hydrochloride lyophilized composition and the preparation method thereof have the benefits that a proper amount of solubilizer (cyclodextrin or cyclodextrin derivative) is added to the gemcitabine hydrochloride lyophilized composition, so thatthe solubility of gemcitabine hydrochloride can be enhanced, the preparation has good reconfigurability and stability, the production cycle of medicine is shortened, the energy consumption is reduced, the gemcitabine hydrochloride lyophilized composition is convenient to store and transport, and security is provided for clinical medication.

Description

technical field [0001] The invention relates to the field of pharmaceutical preparations, in particular to a gemcitabine hydrochloride freeze-dried composition and a preparation method thereof. Background technique [0002] Gemcitabine hydrochloride (gemcitabine hydrochloride) is a pyrimidine antineoplastic drug, its chemical name is 2-deoxy-2,2-difluorodeoxycytidine hydrochloride (β-isomer), and its anti-tumor mechanism is its in vivo Activated by phosphorylation, it becomes an active metabolite, incorporates DNA in cells, and prevents tumor cells from progressing from G1 phase to S phase. Gemcitabine hydrochloride for injection (trade name Gemzar) was developed by Eli Lilly and Company, and was first launched in the United States in 1996. It is indicated for the treatment of locally advanced or metastatic non-small cell lung cancer and pancreatic cancer. [0003] Because gemcitabine hydrochloride has a strong gastrointestinal stimulating effect, it is mainly administered ...

AI Technical Summary

Problems solved by technology

[0013] However, the composition still has the following defects. As everyone knows, hemolytic reaction is a common adverse reaction of cyclodextrin. Tests have shown that under the intravenous route, slight hemolysis will occur when the concentration of cyclodextrin reaches 0.02mol / L. Obvious hemolysis occurs at 0.04mol / L, according to the best ratio of inclusion, that is, the pharmaceutical composition is prepared at a ratio of 1:1 with gemcitabine hydrochloride and cyclodextrin molar ratio, gemcitabine hydrochloride cyclodextrin inclusion compound according to The normal dose is very close to the range of hemolytic reaction, and the risk of hemolytic reaction is greatly increased. However, when the clathrate is prepared with a molar ratio of gemcitabine hydrochloride and cyclodextrin at a ratio of 1:2, obvious hemolytic reaction occurs

In addition, due to the high market price of cyclodextrin, the use of too much cyclodextrin greatly increases the cost of the product

[0014] In view of the above, there is a lack of a gemcitabine hydrochloride freeze-dried composition with excellent performance in the prior art, which not only has better quality stability and safety, but also has a preparation process with lower manufacturing costs and high production efficiency.

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