Delivery system for sustained release of a calcium-channel blocking agent

摘要

A delivery system for sustained release of a calcium-channel blocking agent is adapted for introduction in the cerebrospinal fluid of a subject. The delivery system comprises a solid dispersion product of a calcium-channel blocking agent in a mixture of a (i) first poly(lactide-co-glycolide) having a molecular weight distribution centered around a first number average molecular weight Mn1 and a (ii) second poly(lactide-co-glycolide) having a molecular weight distribution centered around a second number average molecular weight Mn2, wherein Mn1 is in the range of from 2000 to 3000 g/mol and the ratio of Mn1/Mn2 is from 1.8 to 3.5. The delivery system is deposited in the vicinity of or adjacent to a blood vessel showing vasospasm or suspected of developing vasospasm.

主权项

1. A delivery system for sustained release of nicardipine free base, a hydrate or solvate thereof, adapted for introduction into the cerebrospinal fluid of a subject, comprising a solid dispersion product of nicardipine free base, hydrate or solvate thereof, in a mixture of:
(i) a first poly(lactide-co-glycolide) having a molecular weight distribution centered around a first number average molecular weight Mn1 and a lactate:glycolate molar ratio of from 45:55 to 55:45; and (ii) a second poly(lactide-co-glycolide) having a molecular weight distribution centered around a second number average molecular weight Mn2 and a lactate:glycolate molar ratio in the second poly(lactide-co-glycolide) of from 45:55 to 55:45; wherein: Mn1 is in the range of from 2000 to 3000 g/mol and the ratio of Mn1/Mn2 is from 1.8 to 3.5; the nicardipine free base, hydrate or solvate thereof is molecularly dispersed in a monophasic mixture comprising the first poly(lactide-co-glycolide) and the second poly(lactide-co-glycolide); and the solid dispersion product is formed into a predetermined shape prior to introduction into the cerebrospinal fluid of said subject.