Abstract: A device for the sustained release in vivo of a water soluble, biologically active agent wherein the agent is susceptible to aggregation comprising a drug delivery device and aggregation-stabilized, biologically active agent wherein the aggregation-stabilized agent is disposed within the drug delivery device.

Abstract: A pharmaceutical composition for the sustained release of human growth hormone from a polymer matrix is disclosed. The pharmaceutical composition comprises a biocompatible polymer, particles of metal cation-complexed human growth hormone wherein said particles are dispersed within the biocompatible polymer and an aqueous injection vehicle.

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: Drugs, especially low aqueous solubility drugs, are provided in a porous matrix form, preferably microparticles, which enhances dissolution of the drug in aqueous media. The drug matrices preferably are made using a process that includes (i) dissolving a drug, preferably a drug having low aqueous solubility, in a volatile solvent to form a drug solution, (ii) combining at least one pore forming agent with the drug solution to form an emulsion, suspension, or second solution and hydrophilic or hydrophobic excipients that stabilize the drug and inhibit crystallization, and (iii) removing the volatile solvent and pore forming agent from the emulsion, suspension, or second solution to yield the porous matrix of drug. Hydrophobic or hydrophilic excipients may be selected to stabilize the drug in crystalline form by inhibiting crystal growth or to stabilize the drug in amorphous form by preventing crystallization.

Abstract: A lipid or other hydrophobic or amphiphilic compound (collectively referred to herein as “hydrophobic compounds”) is integrated into a polymeric matrix for drug delivery to alter drug release kinetics. In embodiments where the drug is water soluble, the drug is released over longer periods of time as compared to release from the polymeric matrix not incorporating the hydrophobic compound into the polymeric material. In contrast to methods in which a surfactant or lipid is added as an excipient, the hydrophobic compound is actually integrated into the polymeric matrix, thereby modifying the diffusion of water into the microparticle and diffusion of solubilized drug out of the matrix. The integrated hydrophobic compound also prolongs degradation of hydrolytically unstable polymers forming the matrix, further delaying release of encapsulated drug.

Abstract: Drugs, especially low aqueous solubility drugs, are provided in a porous matrix form, preferably microparticles, which enhances dissolution of the drug in aqueous media. The drug matrices preferably are made using a process that includes (i) dissolving a drug, preferably a drug having low aqueous solubility, in a volatile solvent to form a drug solution, (ii) combining at least one pore forming agent with the drug solution to form an emulsion, suspension, or second solution, and (iii) removing the volatile solvent and pore forming agent from the emulsion, suspension, or second solution to yield the porous matrix of drug. The pore forming agent can be either a volatile liquid that is immiscible with the drug solvent or a volatile solid compound, preferably a volatile salt. In a preferred embodiment, spray drying is used to remove the solvents and the pore forming agent.

Abstract: This invention relates to a composition, and method of forming said composition, for the controlled release of interferon. The controlled release composition of this invention comprises a biocompatible polymer and particles of metal cation-stabilized interferon, wherein the particles are dispersed within the biocompatible polymer. The method of the invention, for producing a composition for the controlled release of interferon, includes dissolving a polymer in a polymer solvent to form a polymer solution, dispersing particles of metal cation stabilized-interferon particles in the polymer solution, and then solidifying the polymer to form a polymeric matrix containing a dispersion of the interferon particles.

Abstract: Paclitaxel is provided in a porous matrix form, which allows the drug to be formulated without Cremophor and administered as a bolus. The paclitaxel matrices preferably are made using a process that includes (i) dissolving paclitaxel in a volatile solvent to form a paclitaxel solution, (ii) combining at least one pore forming agent with the paclitaxel solution to form an emulsion, suspension, or second solution, and (iii) removing the volatile solvent and pore forming agent from the emulsion, suspension, or second solution to yield the porous matrix of paclitaxel. The pore forming agent can be either a volatile liquid that is immiscible with the paclitaxel solvent or a volatile solid compound, preferably a volatile salt. In a preferred embodiment, spray drying is used to remove the solvents and the pore forming agent.

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: A lipid or other hydrophobic or amphiphilic compound (collectively referred to herein as “hydrophobic compounds”) is integrated into a polymeric matrix for drug delivery to alter drug release kinetics. In embodiments where the drug is water soluble, the drug is released over longer periods of time as compared to release from the polymeric matrix not incorporating the hydrophobic compound into the polymeric material. In contrast to methods in which a surfactant or lipid is added as an excipient, the hydrophobic compound is actually integrated into the polymeric matrix, thereby modifying the diffusion of water into the microparticle and diffusion of solubilized drug out of the matrix. The integrated hydrophobic compound also prolongs degradation of hydrolytically unstable polymers forming the matrix, further delaying release of encapsulated drug.

Abstract: Improved spray drying methods of have been developed. The spray drying method includes use of a primary drying chamber and a secondary drying apparatus which includes tubing having a length sufficient to increase the contact time between the drying gas and the droplets/particles to dry the particles to the extent desired, at a drying rate and temperature which would be too low to provide adequate drying without the secondary drying apparatus. The secondary drying apparatus increases the drying efficiency of the spray dryer system without increasing the drying rate, while minimizing loss in yield. The ratio of the length of tubing to the length of the primary drying chamber is at least 2:1. The tubing diameter is substantially smaller than the diameter of the primary drying chamber, such that the particles move at higher velocity through the tubing to minimize product losses.

Abstract: Improved spray drying apparati, and methods of use thereof, have been developed. The spray drying equipment includes a primary drying chamber and a secondary drying apparatus which includes tubing having a length sufficient to increase the contact time between the drying gas and the droplets/particles to dry the particles to the extent desired, at a drying rate and temperature which would be too low to provide adequate drying without the secondary drying apparatus. The secondary drying apparatus increases the drying efficiency of the spray dryer system without increasing the drying rate, while minimizing loss in yield. The ratio of the length of tubing to the length of the primary drying chamber is at least 2:1. The tubing diameter is substantially smaller than the diameter of the primary drying chamber, such that the particles move at higher velocity through the tubing to minimize product losses.

Abstract: Improved spray drying apparati, and methods of use thereof, have been developed. The spray drying equipment includes a primary drying chamber and a secondary drying apparatus which includes tubing having a length sufficient to increase the contact time between the drying gas and the droplets/particles to dry the particles to the extent desired, at a drying rate and temperature which would be too low to provide adequate drying without the secondary drying apparatus. The secondary drying apparatus increases the drying efficiency of the spray dryer system without increasing the drying rate, while minimizing loss in yield The ratio of the length of tubing to the length of the primary drying chamber is at least 2:1. The tubing diameter is substantially smaller than the diameter of the primary drying chamber, such that the particles move at higher velocity through the tubing to minimize product losses.

Abstract: A lipid or other hydrophobic or amphiphilic compound (collectively referred to herein as “hydrophobic compounds”) is integrated into a polymeric matrix for drug delivery to alter drug release kinetics. In embodiments where the drug is water soluble, the drug is released over longer periods of time as compared to release from the polymeric matrix not incorporating the hydrophobic compound into the polymeric material. In contrast to methods in which a surfactant or lipid is added as an excipient, the hydrophobic compound is actually integrated into the polymeric matrix, thereby modifying the diffusion of water into the microparticle and diffusion of solubilized drug out of the matrix. The integrated hydrophobic compound also prolongs degradation of hydrolytically unstable polymers forming the matrix, further delaying release of encapsulated drug.

Abstract: A lipid or other hydrophobic or amphiphilic compound (collectively referred to herein as “hydrophobic compounds”) is integrated into a polymeric matrix for drug delivery to alter drug release kinetics. In embodiments where the drug is water soluble, the drug is released over longer periods of time as compared to release from the polymeric matrix not incorporating the hydrophobic compound into the polymeric material. In contrast to methods in which a surfactant or lipid is added as an excipient, the hydrophobic compound is actually integrated into the polymeric matrix, thereby modifying the diffusion of water into the microparticle and diffusion of solubilized drug out of the matrix. The integrated hydrophobic compound also prolongs degradation of hydrolytically unstable polymers forming the matrix, further delaying release of encapsulated drug.

Abstract: This invention relates to a composition, and method of forming said composition, for the controlled release of interferon. The controlled release composition of this invention comprises a biocompatible polymer and particles of metal cation-stabilized interferon, wherein the particles are dispersed within the biocompatible polymer. The method of the invention, for producing a composition for the controlled release of interferon, includes dissolving a polymer in a polymer solvent to form a polymer solution, dispersing particles of metal cation-stabilized interferon particles in the polymer solution, and then solidifying the polymer to form a polymeric matrix containing a dispersion of the interferon particles.

Abstract: It has been discovered that the incorporation of fluorinated gases, especially a perfluorocarbon such as octafluoropropane, into synthetic polymeric microparticles, significantly enhances echogenicity as compared with microparticles having air incorporated therein. The microencapsulated perfluorocarbon is manufactured with a diameter suitable for the targeted tissue to be imaged, for example, for intravenous or oral administration. In one embodiment, bioadhesive microparticles are formed for enhanced imaging of mucosal surfaces.

Abstract: The method of the invention for producing a composition for the sustained release of biologically active hGH includes dissolving a biocompatible polymer in a polymer solvent to form a polymer solution, dispersing particles of biologically active, metal cation-stabilized hGH in the polymer solution, and then solidifying the polymer to form a polymeric matrix containing a dispersion of said hGH particles.

Abstract: It has been discovered microparticles formed from natural or synthetic polymer with thicker walls have significantly enhanced echogenicity as compared with microparticles having thinner walls. The effect of wall thickness has been determined experimentally as well as inserted into a formula for use in predicting the optimum conditions. In the preferred embodiment, the polymers are synthetic biodegradable polymers and the wall thickness is between about 100 and 660 nm, although wall thicknesses from about 20 nm to in excess of 500 nm can be used. The microparticles are manufactured with a diameter suitable for the targeted tissue to be imaged, for example, with a diameter of between 0.5 and 8 microns for intravascular administration, and a diameter of between 0.5 and 5 mm for oral administration for imaging of the gastrointestinal tract or other lumens.

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.