Dispersible phospholipid stabilized microparticles

Abstract

Rapidly dispersing solid dry therapeutic dosage form comprised of a water insoluble compound existing as a nanometer or micrometer particulate solid which is surface stabilized by the presence of at least one phospholipid, the particulate solid being dispersed throughout a bulking matrix. When the dosage form is introduced into an aqueous environment the bulking matrix is substantially completely dissolves within less than 2 minutes thereby releasing the water insoluble particulate solid in an unaggregated and / or unagglomerated state. The matrix is composed of a water insoluble substance or therapeutically useful water insoluble or poorly water soluble compound, a phospholipid and optionally also at least one non-ionic, anionic, cationic, or amphipathic surfactant, together with a matrix or bulking agent and if needed a release agent. The volume weighted mean particle size of the water insoluble particle is 5 micrometers or less.

Description

CROSS-REFERENCE TO RELATED APPLICATION[0001]This is a continuation of U.S. patent application Ser. No. 09 / 443,863, filed Nov. 19, 1999, which claims the benefit of U.S. provisional application No. 60 / 109,202, filed Nov. 20, 1998. The disclosures of the '863 and '202 applications are incorporated by reference.FIELD OF THE INVENTION[0002]This invention relates to compositions comprised of water-insoluble or poorly soluble drug particles of a size of about 0.05 to 10 micrometers having a surface modifying agent or combination of agents, of which at least one is a phospholipid, adsorbed on to the surface thereof. The composition includes a matrix-forming agent(s) which is present in an amount sufficient to allow freeze-drying and subsequent release of the surface coated drug particles upon contact with an aqueous environment. Small surface coated particles are sometimes referred to as MicroCrystals (in U.S. Pat. Nos. 5,091,187 and 5,091,188 patents), MicroParticles (WO 98 / 07414 and PA S...

AI Technical Summary

Benefits of technology

[0012]According to this invention the microparticle suspension so produced is further admixed with surface modifying agent(s) and / or matrix-forming agent(s) which are present in an amount sufficient to allow freeze-drying and subsequent release of the surface coated drug particles upon contact with an aqueous environment. The selection of these components serves to minimize the tendency of microparticles to aggregate upon drying. Such aggregates are extremely difficult to redisperse due to the very high particle surface area which facilitates the degree of contact available to interacting particles resulting in irreversible lattices.

[0013]Small particle sizes of drugs are often needed in drug formulation development in order to maximize surface area, bioavailability, and dissolution requirements. The introduction of a suitable matrix-forming agent(s) in the above noted process serves to stabilize the phospholipid coated drug particle during the freeze-drying process and in the resulting freeze-dried product by suppressing any tendency of particle agglomeration or particle growth.

Problems solved by technology

Such aggregates are extremely difficult to redisperse due to the very high particle surface area which facilitates the degree of contact available to interacting particles resulting in irreversible lattices.