A kind of pramipexole sustained-release microsphere and preparation method thereof

Abstract

The invention discloses a pramipexole sustained-release microsphere. The pramipexole drug is prepared into the pramipexole sustained-release microsphere by an emulsification (O / W)-solvent volatilization method, and the prepared sustained-release microsphere has drug-loading properties. With the advantages of high dosage and high encapsulation efficiency, it can realize the stable release of drugs, the preparation process is simple, and it is easy for industrial scale-up.

Description

technical field [0001] The invention belongs to the technical field of medicine, and relates to a pramipexole sustained-release microsphere and a preparation method thereof. Background technique [0002] With the rapid development of the global aging society, anti-Parkinson's disease (PD) prescription drugs have attracted much attention in recent years. The main varieties of anti-Parkinson drugs are: pramipexole, encatabone, ropinirole, pseudodopamines and rasagiline. Pramipexole (trade name Senfulol) is a second-generation potent, selective non-ergot alkaloid dopamine D2 receptor agonist for the treatment of primary Parkinson's disease, which can be used alone or in combination with levodopa, available Throughout the disease stages up to advanced Parkinson's disease. Pramipexole can significantly improve the motor symptoms of patients with early and late Parkinson's disease, and can also improve the symptoms of depression associated with Parkinson's disease. Pramipexole ...

AI Technical Summary

Problems solved by technology

When adopting the water-in-oil-in-water double emulsion method to prepare microspheres, there are following disadvantages: (1) the stability change problem of water-in-oil colostrum, whether it is the water-in-oil type colostrum before secondary emulsification, has a great influence on drug loading The amount of colostrum has a great influence, and the stability of colostrum needs to be placed statically for a long time by visual evaluation (simple colostrum is divided into excellent, medium, and poor) or stratification. In pilot scale or large-scale production, there are big problem

(2) The particle size of the colostrum prepared each time is quite different, which directly affects the particle size of the prepared microspheres

(3) During the scale-up production process of microspheres prepared by the water-in-oil-in-water double emulsion method, the solvent volatilization time is prolonged due to the increase of the total amount of the oil phase, which causes the drug to be released from the microspheres to be released into the water phase in advance, thereby The drug loading capacity of the microspheres is greatly reduced

The process is cumbersome, and the content uniformity is difficult to guarantee, so it is not suitable for industrial scale-up production

[0007] At present, the commonly used pramipexole hydrochloride preparations still have a lot of problems due to the preparation process and the dosage relationship between the components: on the one hand, because pramipexole hydrochloride has a bitter taste, the pramipexole hydrochloride preparations have a bitter taste. Poor, the existing preparations usually solve the mouthfeel problem by adding sweeteners and flavoring agents, but the addition of sweeteners and flavoring agents has an impact on the dispersion and absorption of drug molecules; on the other hand, hydrochloric acid in the preparation The dissolution rate and content uniformity of pramipexole are low, and the pharmacodynamic molecules are also lacking in uniform release and dispersion

[0008] Patent CN111212640A discloses a pharmaceutically acceptable salt of pramipexole, pramipexole pamoate; compared with pramipexole hydrochloride, this salt shows unique advantages: significantly reduced solubility in water, no bitter taste, Good stability, but not yet used in the development of long-acting sustained-release dosage forms

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