Azacitidine lyophilized powder for injection and preparation method thereof

Abstract

The invention provides azacitidine lyophilized powder for injection. The azacitidine lyophilized powder is prepared from, by weight, 2-8 parts of azacitidine, 2-8 parts of mannitol, 100-300 parts of acetonitrile and 684-896 parts of water. The invention further provides a preparation method of the azacitidine lyophilized powder for injection. The preparation method comprises the steps that part ofthe water for injection is added into a liquid preparation tank; 100-300 parts by weight of acetonitrile is added, and stirring is conducted until the mixture is clear; 2-8 parts by weight of mannitol is added, stirring is conducted until the mixture is completely dissolved, and the temperature is lowered to be 0-4 DEG C; 2-8 parts by weight of a pre-micronized raw azacitidine material is weighed, washed with part of the remaining water for injection and then added into the liquid preparation tank, intensive stirring is conducted until the mixture is dissolved, and the water for injection isadded to reach the constant volume of 1000 parts; after sterile filtration, filling and freeze-drying, the preparation product is obtained. The particle size of the product and the total impurity level of the product can be effectively controlled, the stripping curve and other bioequivalence indexes of the product are equivalent to those of an original research product, and the total impurity level is lower than that of the original research product.

Description

technical field [0001] The invention relates to the technical field of medicine, in particular to azacitidine freeze-dried powder for injection. Background technique [0002] Azacitidine is a cytidine analog that is mainly used in the treatment of myelodysplastic syndromes. U.S. FDA approved this medicine to go on the market in 2004, because the active ingredient azacitidine of this medicine is poor in stability, hydrolyzes rapidly in water, so the preparation on the market is a powder injection preparation. [0003] Azacitidine freeze-dried powder for injection is now on the market in the United States and China, and only the original product is currently on the market in my country. The difficulty in the development of this product is that the product has two administration methods, one is intravenous infusion after reconstitution into a solution, and the other is subcutaneous injection after reconstitution into a suspension. Among them, the drug delivery method of subcu...

AI Technical Summary

Problems solved by technology

Since azacitidine is almost insoluble in acetonitrile, although a high proportion of acetonitrile will delay the degradation rate of hydrolyzed impurities, it will also hinder the improvement of the dissolution rate of the raw material drug, and a high proportion of acetonitrile requires a longer dissolution time, making it The inhibitory effect on the impurity level in the dissolution stage of the raw material drug is limited, and the initial impurity level after the drug solution is constant will not be significantly improved

Moreover, the document mentions that the crystal forms prepared by the patent are Form IV to Form VIII, which are significantly different from Form I and Form II of the original research product, so its particle size may also be different from that of the original research product. The difference in diameter usually results in a significant difference in the dissolution profile. Therefore, the product cannot pass the requirements of the US FDA bioequivalence guidelines and is not practical.

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