초록 ▼

The described invention provides a biodegradable, biocompatible delivery system of flowable sustained release microparticulate composition of a substantially pure crystalline form of a bioactive agent such as, for example, nimodipine, a process of preparing a therapeutic form of a substantially pure

The described invention provides a biodegradable, biocompatible delivery system of flowable sustained release microparticulate composition of a substantially pure crystalline form of a bioactive agent such as, for example, nimodipine, a process of preparing a therapeutic form of a substantially pure crystalline form of the bioactive agent and a method for treating an interruption of a cerebral artery in a subarachnoid space at risk of interruption caused by brain injury in a mammal, which reduces signs or symptoms of at least one delayed complication associated with brain injury.

대표청구항 ▼

1. A semisolid, biodegradable, biocompatible delivery system capable of sustained release kinetics comprising: (i) a flowable microparticulate formulation comprising a crystalline polymorphic Form I of Nimodipine characterized by a melting range of 122° C. to 127° C. as measured by Differential Scan

1. A semisolid, biodegradable, biocompatible delivery system capable of sustained release kinetics comprising: (i) a flowable microparticulate formulation comprising a crystalline polymorphic Form I of Nimodipine characterized by a melting range of 122° C. to 127° C. as measured by Differential Scanning calorimetry (DSC), the microparticulate formulation being characterized by:(a) a plurality of microparticles wherein each microparticle comprises a matrix;(b) dispersal of the polymorphic Form I of Nimodipine throughout each microparticle, and(c) a load of at least 70 percent by weight, relative to the total weight of Nimodipine, of Form I of Nimodipine;(d) wherein said matrix comprises a biodegradable polymer selected from the group consisting of polylactide-polyglycolide, poly(orthoester), and poly(anhydride); and(e) a pharmaceutically acceptable carrier,the delivery system being characterized by delayed release of the polymorphic Form I of Nimodipine from the delivery system, wherein one half of the polymorphic Form I of Nimodipine is released from the delivery system within 1 day to 30 days in vivo. 2. The delivery system according to claim 1, wherein the microparticulate formulation comprises a powder suspension of microparticles. 3. The delivery system according to claim 1, wherein Nimodipine load of the formulation contained within the delivery system ranges from about 25% (by weight) to 75% by weight relative to the total weight of the formulation. 4. The semisolid, biodegradable, biocompatible delivery system capable of sustained release kinetics according to claim 1, wherein the microparticulate formulation is characterized by a Nimodipine load of from about 25% to 75% by weight relative to the total weight of the formulation. 5. The semisolid, biodegradable, biocompatible delivery system capable of sustained release kinetics according to claim 1, wherein the flowable microparticulate formulation is prepared by a process comprising: (a) providing the polymorphic Form I of Nimodipine characterized by a melting range of 122° C. to 127° C. as measured by Differential Scanning calorimetry (DSC);(b) adding the polymorphic Form I of Nimodipine to a polymer solution, thereby creating a mixture of the polymorphic Form I of Nimodipine and the polymer solution;wherein the polymer solution comprises a solvent and a biodegradable polymer, the solvent in the polymer solution comprises ethyl acetate or dichloromethane or a mixture thereof and the biodegradable polymer is selected from the group consisting of polylactide, polylactide-co-glycolide, poly(orthoester), and poly(anhydride);(c) homogenizing the mixture to form a disperse phase;(d) mixing the disperse phase with a continuous phase comprising a continuous process medium, thereby forming an emulsion comprising the polymorphic Form I of Nimodipine;(e) forming and extracting the microparticles comprising the polymorphic form of Nimodipine; and(f) drying the microparticles for a time from 4 to 48 hours,wherein the microparticulate formulation is characterized by:(i) a plurality of microparticles;(ii) dispersal of the polymorphic form I of Nimodipine throughout each microparticle; and(iii) a load of at least 70% by weight relative to the total weight of Nimodipine of Form I of Nimodipine.