Pharmaceutical composition for improving in-vitro dissolution and liquidity of spironolactone

Abstract

The invention belongs to the field of pharmaceutical preparations, and relates to a pharmaceutical composition for improving in-vitro dissolution and liquidity of spironolactone and a preparation method of the pharmaceutical composition. The pharmaceutical composition is mainly characterized by being prepared from an indissolvable drug spironolactone and a carrier material, wherein the mass ratio of the drug to the carrier is 1:3-1:10, the pharmaceutical composition prepared through a hot-melt extrusion technique is solid dispersion, the spironolactone is dispersed into the carrier in a molecular or amorphous mode, and therefore the in-vitro dissolution of the spironolactone is significantly improved. After the spironolactone is smashed, the liquidity of the spironolactone is significantly improved, and the smashed spironolactone can be directly filled into capsules or directly subpackaged by serving as powder and granules or used by being mixed with other pharmaceutical auxiliary materials to prepare tablets. Compared with traditional methods such as the solvent method and the solvent-melt method, the adopted hot-melt extrusion technique has the advantages of being capable of not using an organic solvent, safe, free of pollution, stable in technology, capable of achieving continuous operation, easily achieving industrialized enlarged production and improving the liquidity without needing to add a flow aid and the like.

Description

technical field [0001] The invention belongs to the field of pharmaceutical preparations, and relates to a pharmaceutical composition for improving spironolactone dissolution and fluidity in vitro and a preparation method thereof. Background technique [0002] The chemical name of Spironolactone is 17β-hydroxy-3-oxo-7α-(acetylthio)-17α-pregna-4-ene-21-carboxylic acid γ-lactone, and its chemical structure is very similar to that of aldosterone, so it is used as Aldosterone competitive inhibitor, acts on the cortex of the distal convoluted tubule and collecting duct, antagonizes the potassium excretion and sodium preservation of aldosterone on the above parts, and promotes Na + and water discharge, reducing K + The secretion of the diuretic, which produces a diuretic effect, is called a "potassium-sparing diuretic." The diuretic effect of spironolactone is slow, mild and long-lasting, so it is often used in combination with the strong diuretic furosemide clinically, mainly f...

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Problems solved by technology

[0005] Chinese patent CN201210221305.6 discloses a kind of oil-in-water compound spironolactone nanoemulsion medicine, although preparing spironolactone into nanoemulsion can improve its in vitro dissolution and bioavailability, but the prescription needs to add surfactant, cosurfactone, Oil and other auxiliary materials, the preparation process is relatively complicated, and the route of administration is also limited; Chinese patent CN201410735870.3 discloses a spironolactone composition freeze-dried tablet and its preparation method, and spironolactone, starch, and sucrose are prepared into freeze-dried Tablets, but spironolactone still exists in crystal form, and the fluidity problem has not been significantly improved; Chinese patent CN200780020789.5 discloses a solid dispersion of a poorly soluble drug in a graft copolymer, mainly using polyvinyl alcohol- Polyethylene glycol graft copolymer is used as a carrier to improve the dissolution of insoluble drugs in vitro through thermal graded extrusion technology, but the melting point of spironolactone raw material is 209°C, which is relatively high, and the carrier polyvinyl alcohol-polyethylene glycol graft copolymer The glass transition temperature is low. In the extrudate obtained under this process, spironolactone still exists in the form of crystals, which fails to significantly improve the in vitro dissolution, and the obtained extrudate needs to be added with micronized silica gel to further improve the fluidity of the drug.

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