A kind of doxycycline hydrochloride freeze-dried powder for injection and preparation method thereof

Abstract

The invention relates to a doxycycline hydrochloride freeze-dried powder for injection and a preparation method thereof. The freeze-dried powder comprises an active ingredient doxycycline hydrochloride, a stabilizer, an excipient and water for injection. The stabilizer is vitamin C, cysteine ​​hydrochloride; the excipient is lactose. The weight ratio of doxycycline hydrochloride: vitamin C: cysteine ​​hydrochloride: lactose is 10-20: 40-60: 0.5-1: 30-40. Doxycycline hydrochloride, vitamin C, cysteine ​​hydrochloride, and lactose can form a good co-crystal compound. In the preparation method of the freeze-dried powder, the pre-freezing adopts the method of repeated heating and cooling, and the analytical drying temperature is appropriately increased. The freeze-dried powder prepared by the technical scheme is well formed, has a plump appearance, is loose and porous, and has good resolubility. The moisture limit of the freeze-dried preparation is controllable, the quality is stable, and the storage period of the medicine can be effectively extended.

Description

technical field [0001] The invention belongs to the field of pharmaceutical preparations, in particular to a doxycycline hydrochloride freeze-dried powder for injection and a preparation method thereof. Background technique [0002] The chemical name of doxycycline hydrochloride is: 6-methyl-4-(dimethylamino)-3,5,10,12,12α-pentahydroxy-1,11-dioxo-1,4,4α,5 ,5α,6,11,12α-Octahydro-2-tetracenecarboxamide hydrochloride hemiethanol hemihydrate. The structural formula is: [0003] [0004] Doxycycline hydrochloride is a broad-spectrum semi-synthetic tetracycline antibiotic. Its antibacterial spectrum is similar to that of tetracycline, and its antibacterial effect is 10 times stronger. The medicine has strong water solubility, good absorption, wide distribution, more clinical application and good effect, and its antibacterial activity in vivo and in vitro is stronger than that of tetracycline. This product can inhibit Gram-negative bacteria, positive bacteria, spirochetes, ri...

AI Technical Summary

Problems solved by technology

This patent does not control vitamin C-related substances. Although the freeze-drying curve of this patent has a long sublimation time, most of the free water can be removed, but the analytical drying temperature is low, and the drying time is too short to be conducive to the sublimation of bound water. Product moisture may be high

[0008] Chinese patent CN105078905A discloses a preparation method of doxycycline hydrochloride freeze-dried preparations. The patent test example involves a repeated pre-freezing process. After freeze-drying, the surface of the product is bubbling, with obvious shrinkage, and cannot be formed.

This repeated pre-freezing process cannot meet the characteristics of "cooling and freezing the product first, then raising the temperature to near the eutectic point, and then cooling and freezing", so the product after freeze-drying with this pre-freezing process is unqualified

Moreover, this patent does not control the vitamin C content and related substances

[0009] To sum up, the current formula of doxycycline hydrochloride freeze-dried powder contains vitamin C as an antioxidant, and the dosage is large, and the current research does not control the degraded impurities of vitamin C after oxidation

Moreover, the moisture content of the freeze-dried powder is not effectively controlled in the freeze-drying process. During long-term storage, the drug is easily degraded, the related substances increase, the stability and quality cannot be guaranteed, and the service life of the drug is greatly shortened.

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