Abstract: Microparticles that include a bisphosphonate and a polymer are produced by a method that includes forming a water-in-oil emulsion by mixing an aqueous solution of the bisphosphonate with a combination of a biocompatible polymer and a polymer solvent. At least one aqueous liquid can be mixed with the water-in-oil emulsion to form a water-in-oil-in-water emulsion and to extract the polymer solvent from the polymer, thereby forming the microparticles. Methods of treating a patient in need of therapy include administering the microparticles described to the patient. In one embodiment, the microparticles are formulated for the sustained release of the bisphosphonate.

Abstract: A method for forming microparticles includes fragmenting solid particles that include a biologically active agent, a biocompatible polymer and a solvent, thereby producing fragmented solid particles, and separating the solvent from the fragmented solid particles, thereby forming the microparticles. The method can also include the steps of forming a mixture of the biologically active agent, the biocompatible polymer and the solvent, and freezing the mixture to form the solid particles. The present invention also relates to methods for producing injectable pharmaceutical compositions that include an injectable microparticle population.

Abstract: Apparatus and method for preparing microparticles. An emulsion is formed by combining two phases in a static mixing assembly. The static mixing assembly preferably includes a preblending static mixer and a manifold. The emulsion flows out of the static mixing assembly into a quench liquid whereby droplets of the emulsion form microparticles. The residence time of the emulsion in the static mixing assembly is controlled to obtain a predetermined particle size distribution of the resulting microparticles.

Abstract: Apparatus and method for preparing microparticles using in-line solvent extraction. An emulsion is formed by combining two phases in a static mixer. The emulsion is combined with an extraction liquid in a blending static mixer. The outflow of the blending static mixer is combined with additional extraction liquid. The additional extraction liquid and the outflow of the blending static mixer can be combined in a vessel, or through the use of a static mixer manifold that includes a plurality of static mixers.

Abstract: Method and apparatus for preparing microparticles using liquid-liquid extraction. A first phase and a second phase are combined to form an emulsion. A portion of the second phase is separated from the emulsion (solvent rich), and the solvent is extracted from the separated second phase, which is then returned (solvent poor) to the emulsion. This process of separation of a solvent rich phase, extraction of solvent, and return of a solvent poor phase, is carried out until a selected level of solvent in the emulsion is achieved. Alternatively, the separated solvent rich phase is not returned to the emulsion, but replaced with another solution, such as an aqueous solution, that is free from solvent. The solvent is preferably extracted into an extraction liquid that functions as a “solvent sink” for the solvent.

Abstract: Methods for preparing microparticles having reduced residual solvent levels. Microparticles are contacted with a non-aqueous washing system to reduce the level of residual solvent in the microparticles. Preferred non-aqueous washing systems include 100% ethanol and a blend of ethanol and heptane. A solvent blend of a hardening solvent and a washing solvent can be used to harden and wash microparticles in a single step, thereby eliminating the need for a post-hardening wash step.

Abstract: Apparatus and method for preparing microparticles. An emulsion is formed by combining two phases in a static mixing assembly. The static mixing assembly preferably includes a preblending static mixer and a manifold. The emulsion flows out of the static mixing assembly into a quench liquid whereby droplets of the emulsion form microparticles. The residence time of the emulsion in the static mixing assembly is controlled to obtain a predetermined particle size distribution of the resulting microparticles.

Abstract: Sustained-release microparticle composition. The microparticle composition can be formulated to provide multi-phasic release. In one aspect, the composition includes microparticles having more than one rate of release. In another aspect, the composition includes microparticles that exhibit diffusional release and microparticles that exhibit biodegradation release.

Abstract: The present invention relates to crosslinked polymers, synthesized through ring-opening polymerization of ethylenically unsaturated epoxides, in combination with ?-hydroxy acids using a hydrophilic macroinitiator, such as poly(ethylene glycol), to form substituted copolymers having ethylenically unsaturated functionality randomly distributed along the polyester polymer backbone. That copolymer is subsequently crosslinked to form a hydrogel network. More particularly, the present invention relates to the synthesis of biodegradable poly(?-hydroxy acid-co-glycidyl methacrylate)-block-poly(ethylene glycol)-block-poly(?-hydroxy acid-co-glycidyl methacrylate) copolymers, which are subsequently crosslinked to form hydrogel networks. The invention also relates to the use of these hydrogel networks in various applications, in particular, for the controlled release of drugs and proteins.

Abstract: The present invention relates to a method for forming microparticles of a material from microdroplets of a solution, wherein the solution comprises the material dissolved in a solvent. The method includes the steps of directing the microdroplets into a freezing zone, wherein the freezing zone is surrounded by a liquified gas, and wherein the microdroplets freeze. The frozen microdroplets are then mixed with a liquid non-solvent, whereby the solvent is extracted into the non-solvent, thereby forming the microparticles.

Abstract: Method and apparatus for preparing microparticles using liquid-liquid extraction. A first phase and a second phase are combined to form an emulsion. A portion of the second phase is separated from the emulsion (solvent rich), and the solvent is extracted from the separated second phase, which is then returned (solvent poor) to the emulsion. This process of separation of a solvent rich phase, extraction of solvent, and return of a solvent poor phase, is carried out until a selected level of solvent in the emulsion is achieved. Alternatively, the separated solvent rich phase is not returned to the emulsion, but replaced with another solution, such as an aqueous solution, that is free from solvent. The solvent is preferably extracted into an extraction liquid that functions as a “solvent sink” for the solvent.

Abstract: The present invention relates to a polymer paste and a sustained release composition comprising the paste and a biologically active agent. The polymer paste comprises a biocompatible, biodegradable polymer having an inherent viscosity of about 0.12 dL/g or less and a viscosity reducing agent, wherein the biocompatible, biodegradable polymer is present in the polymer paste in at least 60% by weight and the viscosity of the paste is about 400 cP or less. The sustained release composition comprises a biologically active agent and a polymer paste comprising a biocompatible, biodegradable polymer having an inherent viscosity of about 0.12 dL/g or less and a viscosity reducing agent, wherein the biocompatible, biodegradable polymer is present in the polymer paste in at least 60% by weight and the viscosity of the sustained release composition is about 400 cP or less. In a particular embodiment, the sustained release composition is injectable.

Abstract: The present invention relates to a composition for the modulated release of a biologically active agent. The composition comprises a biocompatible polymeric matrix, a biologically active agent which is dispersed within the polymeric matrix, and a metal cation component which is separately dispersed within the polymeric matrix, whereby the metal cation component modulates the release of the biologically active agent from the polymeric matrix. The present invention also relates to a method for modulating the release of a biologically active agent from a biocompatible polymeric matrix, comprising the steps of dissolving a biocompatible polymer in a solvent to form a polymer solution and also separately dispersing a metal cation component and a biologically active agent within the polymer solution.

Abstract: Methods for preparing microparticles having reduced residual solvent levels. Microparticles are contacted with a non-aqueous washing system to reduce the level of residual solvent in the microparticles. Preferred non-aqueous washing systems include 100% ethanol and a blend of ethanol and heptane. A solvent blend of a hardening solvent and a washing solvent can be used to harden and wash microparticles in a single step, thereby eliminating the need for a post-hardening wash step.

Abstract: The invention relates to an improved method for administering live cells to a patient and compositions useful in the method. The composition comprises live cells and biocompatible, biodegradable polymer microparticles. The cells and microparticles of the cell/microparticle composition can be contacted immediately prior to administration, or can be contacted in culture for a specified period of time prior to administration. In the method of the invention, an effective amount of the cell/microparticle composition is administered to a patient in need thereof by injection to a treatment site of the patient to provide a therapeutic effect in the patient. The therapeutic effect can be, for example, the formation of new tissue at the treatment site, or the production and secretion of a biologically active secretory molecule at the treatment site. The therapeutic effect resulting from injection of the cell/microparticle composition into a treatment site, is determined by the type of cell present in the composition.

Abstract: The present invention relates to a sustained release composition comprising micron particles of labile agent and a method of preparing and using the sustained release composition. The invention further relates to micron particles of a labile agent and a method of preparing the micron particles.

Abstract: Injectable compositions having improved injectability. The injectable compositions include microparticles suspended in an aqueous injection vehicle having a viscosity of at least 20 cp at 20° C. The increased viscosity of the injection vehicle that constitutes the fluid phase of the suspension significantly reduces in vivo injectability failures. The injectable compositions can be made by mixing dry microparticles with an aqueous injection vehicle to form a suspension, and then mixing the suspension with a viscosity enhancing agent to increase the viscosity of the fluid phase of the suspension to the desired level for improved injectability.

Abstract: A method for preparing biodegradable, biocompatible microparticles. A first phase is_ prepared that includes a biodegradable, biocompatible polymer, an active agent, and a solvent. A second phase is prepared. The first and second phases are combined to form an emulsion in which the first phase is discontinuous and the second phase is continuous. The discontinuous first phase is separated from the continuous second phase. The residual level of solvent in the discontinuous first phase is reduced to less than about 2% by weight.

Abstract: Apparatus and method for preparing microparticles. An emulsion is formed by combining two phases in a static mixing assembly. The static mixing assembly preferably includes a preblending static mixer and a manifold. The emulsion flows out of the static mixing assembly into a quench liquid whereby droplets of the emulsion form microparticles. The residence time of the emulsion in the static mixing assembly is controlled to obtain a predetermined particle size distribution of the resulting microparticles.

Abstract: The present invention relates to crosslinked polymers, synthesized through ring-opening polymerization of ethylenically unsaturated epoxides, in combination with &agr;-hydroxy acids using a hydrophilic macroinitiator, such as poly(ethylene glycol), to form substituted copolymers having ethylenically unsaturated functionality randomly distributed along the polyester polymer backbone. That copolymer is subsequently crosslinked to form a hydrogel network. More particularly, the present invention relates to the synthesis of biodegradable poly(&agr;-hydroxy acid-co-glycidyl methacrylate)-block-poly(ethylene glycol)-block-poly(&agr;-hydroxy acid-co-glycidyl methacrylate) copolymers, which are subsequently crosslinked to form hydrogel networks. The invention also relates to the use of these hydrogel networks in various applications, in particular, for the controlled release of drugs and proteins.