Abstract: Methods for preparing microparticles having improved flowability to facilitate processing in automated equipment. Microparticles are conditioned so that a flowability index of the microparticles is greater than about 60. The conditioning preferably includes maintaining the microparticles at a conditioning temperature for a period of time. The conditioning can be used with microparticles containing an active agent, and with placebo microparticles, and it is reversible.

Abstract: This invention relates to the discovery of novel polymorphic forms of naltrexone, including solvates, hydrates, anhydrous and other crystalline forms and combinations thereof. These novel forms of naltrexone impart advantages in pharmaceutical formulations incorporating them, including sustained release, or long acting, formulations.

Abstract: Inhalation device and associated method for facilitating inhalation by a patient of powder medicaments contained in a receptacle. The inhalation device has a chamber for receiving the receptacle. A ring is circumferentially coupled to an inner surface of the chamber to achieve a higher reproducible emitted dose of medicament from the receptacle. The inhalation device also includes an improved implement for puncturing the receptacle, requiring less force and experiencing fewer failures. The inhalation device also includes a means for indicating readiness.

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: Methods for preparing microparticles having improved flowability to facilitate processing in automated equipment. Microparticles are conditioned so that a flowability index of the microparticles is greater than about 60. The conditioning preferably includes maintaining the microparticles at a conditioning temperature for a period of time. The conditioning can be used with microparticles containing an active agent, and with placebo microparticles, and it is reversible.

Abstract: This invention relates to compositions for the sustained release of biologically active polypeptides, and methods of forming and using said compositions, for the sustained release of biologically active polypeptides. The sustained release compositions of this invention comprise a biocompatible polymer having dispersed therein, a biologically active polypeptide and a sugar.

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 present invention is directed to a combination treatment of an opioid antagonist e.g., naltrexone and a second compound selected from the group consisting of a GABA B agonist, an NMDA antagonist, a serotonin antagonist, and a cannabinoid antagonist is the key to the successful treatment of a brain reward system disorder. A brain reward system, include but are not limited, to pathological gambling, compulsive alcohol consumption, compulsive over-eating and obesity, compulsive smoking, and drug addiction. The compounds and methods of the present invention effectively reduce the cravings, withdrawal symptoms and negative drug side effects associated with a monotherapy. As such, patient compliance is greatly increased, thereby decreasing relapse of a brain reward system disorder.

Abstract: This invention relates to compositions for the sustained release of biologically active polypeptides, and methods of forming and using said compositions, for the sustained release of biologically active polypeptides. The sustained release compositions of this invention comprise a biocompatible polymer having dispersed therein, a biologically active polypeptide, a sugar and a salting-out salt.

Abstract: Agents, such as bradykinin agonists, increase the transport of pharmaceutical or diagnostic substances that are initially in the bloodstream of a host animal into the interstitial spaces of non-central nervous system solid tumors that may reside in these hosts. A particularly efficacious agent is Cereport™.

Abstract: The present invention pertains to chimeric antibodies that are reactive with transferrin receptors on brain capillary endothelial cells. These antibodies are composed of a variable region, immunologically reactive with the transferrin receptors, that is obtained from one animal source, and a constant region that is derived from an animal source other than the one that provided the variable region. These chimeric antibodies can exist either as isolated entities or as conjugates with a neuropharmaceutical agent for transferal across the blood brain barrier.

Abstract: The present invention pertains to a method for delivering a neuropharmaceutical or diagnostic agent across the blood brain barrier to the brain of a host. The method comprises administering to the host a therapeutically effective amount of an antibody-neuropharmaceutical or diagnostic agent conjugate wherein the antibody is reactive with a transferrin receptor and the antibody is a chimera between the variable region from one animal source and the constant region from a different animal source. Other aspects of this invention include a delivery system comprising an antibody reactive with a transferrin receptor linked to a neuropharmaceutical or diagnostic agent and methods for treating hosts afflicted with a disease associated with a neurological disorder.

Abstract: The present invention pertains to a method for delivering a neuropharmaceutical agent across the blood brain barrier to the brain of a host. The method comprises administering to the host a therapeutically effective amount of a ligand-neuropharmaceutical agent fusion protein wherein the ligand is reactive with a brain capillary endothelial cell receptor. Other aspects of this invention include a delivery system comprising a ligand reactive with a brain capillary endothelial cell receptor which has formed a fusion protein with a neuropharmaceutical agent. The fusion proteins are also aspects of this invention.

Abstract: The present invention pertains to a method for delivering a neuropharmaceutical or diagnostic agent across the blood brain barrier to the brain of a host. The method comprises administering to the host a therapeutically effective amount of an antibody-neuropharmaceutical or diagnostic agent conjugate wherein the antibody is reactive with a transferrin receptor. Other aspects of this invention include a delivery system comprising an antibody reactive with a transferrin receptor linked to a neuropharmaceutical or diagnostic agent and methods for treating hosts afflicted with a disease associated with a neurological disorder.

Abstract: A method for forming polymer/drug microparticles comprising the steps of (1) forming a polymer solution/drug mixture comprising a polymer dissolved in an organic solvent and a suspended labile drug; (2) removing the solvent from the polymer solution/drug mixture, thereby forming a solid polymer/drug matrix; and (3) fragmenting the polymer/drug matrix at a temperature below the glass transition temperature of the polymer/drug matrix, thereby forming polymer/drug matrix microparticles.In one embodiment, the solvent is removed from a polymer solution/drug mixture by freezing the polymer solution/drug mixture and extracting the solvent from the resulting solid polymer solution/drug matrix. The polymer can be a biocompatible polymer, such as poly(lactic acid-co-glycolic acid). The drug can be a labile drug, such as a protein, or a polynucleotide. Another embodiment of the present invention includes the polymer/drug matrix microparticles which are formed by the method outlined above.

Abstract: A composition, and methods of forming and using said composition, for the sustained release of non-aggregated, biologically active, erythropoietin (EPO). The sustained release composition of this invention comprises a polymeric matrix of a biocompatible polymer and particles of biologically active, aggregation-stabilized EPO, wherein said particles are dispersed within the biocompatible polymer.The method of the invention for producing a composition for the sustained release of biologically active EPO, includes dissolving a biocompatible polymer in a polymer solvent to form a polymer solution, dispersing particles of biologically active, aggregation-stabilized EPO in the polymer solution, and then solidifying the polymer to form a polymeric matrix containing a dispersion of said EPO particles.The method for using a composition of the invention is a method for providing a therapeutically effective blood level of biologically active, non-aggregated erythropoietin in a subject for a sustained period.

Abstract: Peptides called receptor mediated permeabilizers (RMP) increase the permeability of the blood-brain barrier to molecules such as therapeutic agents or diagnostic agents. The permeabilizer A-7 or conformational analogues can be intravenously co-administered to a host together with molecules whose desired destination is the interstitial fluid compartment of the brain. Alternatively, the permeabilizer A-7 or conformational analogues can be administered sequentially with the molecule(s) of interest and these molecules can also be administered by routes other than intravascular. The permeabilizer A-7 or conformational analogues allow these molecules to penetrate the blood-brain barrier and arrive in the interstitial fluid.

Abstract: A composition, and methods of forming and using said composition, for the sustained release of non-aggregated, biologically active, erythropoietin (EPO). The sustained release composition of this invention comprises a polymeric matrix of a biocompatible polymer and particles of biologically active, aggregation-stabilized EPO, wherein said particles are dispersed within the biocompatible polymer. The method of the invention for producing a composition for the sustained release of biologically active EPO, includes dissolving a biocompatible polymer in a polymer solvent to form a polymer solution, dispersing particles of biologically active, aggregation-stabilized EPO in the polymer solution, and then solidifying the polymer to form a polymeric matrix containing a dispersion of said EPO particles. The method for using a composition of the invention is a method for providing a therapeutically effective blood level of biologically active, non-aggregated erythropoietin in a subject for a sustained period.

Abstract: The present invention pertains to a method for delivering a neuropharmaceutical agent across the blood brain barrier to the brain of a host. The method comprises administering to the host a therapeutically effective amount of a ligand-neuropharmaceutical agent fusion protein wherein the ligand is reactive with a brain capillary endothelial cell receptor. Other aspects of this invention include a delivery system comprising a ligand reactive with a brain capillary endothelial cell receptor which has formed a fusion protein with a neuropharmaceutical agent. The fusion proteins are also aspects of this invention.

Abstract: The method of using the sustained release composition of the present invention comprises providing a therapeutically effective blood level of biologically active, non-aggregated human growth hormone in a subject for a sustained period by administering to the subject a dose of said sustained release composition.