Southern Biosystems, Inc.

Southern Research Institute

Durect Corporation

Lexicon Pharmaceutical Inc.

Richard J. Holl

John W. Gibson

Arthur J. Tipton

Stacey Meador

Richard J Holl

Arthur J Tipton

John W Gibson

Thomas R Tice

Antonio Belton

David W Mason

Alan H Dean

Laura L Williams

Jinling Chen

Matthew S Deaver

Kalyan Nuguru

Applicator for implantable drug delivery

A coaxial implant has been developed using biodegradable polymeric materials. The coaxial implant has a core containing drug, surrounded by a semi-permeable membrane that controls the rate of release of material from the core. The core containing the drug and the polymer membrane(s) can be the same or different polymer. The core acts as a reservoir of drug, which partitions from the core polymer to form a saturated solution of drug at the polymer membrane.

Zero-order prolonged release coaxial implants

A coaxial implant has been developed using entirely biodegradable polymeric materials. As referred to herein, a coaxial implant is a device having a core containing drug, surrounded by a semi-permeable membrane that controls the rate of release of material from the core. The device is formed by extrusion, using a pre-milling and extruding step to maximize uniformity of drug dispersion within the polymeric material. In one embodiment, the polymer is processed to yield a semi-crystalline polymer, rather than an amorphous polymer. The core containing the drug and the polymer membrane(s) can be the same or different polymer. The polymer can be the same or different composition (i.e., both polycaprolactone, or both poly(lactide-co-glycolide) of different monomer ratios, or polycaprolactone outside of a core of poly(lactide)), of the same or different molecular weights, and of the same or different chemical structure (i.e., crystalline, semi-crystalline or amorphous). The core acts as a reservoir of drug, which partitions from the core polymer to form a saturated solution of at least 10% drug at the polymer membrane.

Processes for making microparticles, preferably containing an active agent, are provided. In a preferred embodiment, the process involves preparing (1) a dispersed phase containing an agent in a solution of polymer and a first solvent; (2) a continuous phase containing a surfactant, and a second solvent that is totally or partially immiscible with the first solvent; and (3) an extraction phase that is a nonsolvent for the polymer, a solvent for the continuous phase components, and a solvent for the first solvent, wherein the first solvent has solubility in the extraction phase of between about 0.1% and 25% by weight. Then, the dispersed phase and the continuous phase are mixed to form an emulsion, and the emulsion is then briefly mixed with a suitable quantity of extraction phase to induce skin formation at the interface of the dispersed and continuous phases. Remaining solvent is removed by an evaporation process step. The emulsification and solvent removal steps are preferably conducted in a continuous process. The brief extraction step prior to evaporation minimizes the loss of active agent from the microparticles, and reduces the required volume of extraction phase as compared to other extraction-based processes. Alternate emulsification methods and solvent removal methods, such as incremental extraction, cryogenic extraction, or membrane separation, also are provided, and can be used in various combinations to make microparticles.

Emulsion-based processes for making microparticles

Processes for making microparticles, preferably containing an active agent, are provided. In a preferred embodiment, the process involves preparing (1) a dispersed phase containing an agent in a solution of polymer and a first solvent; (2) a continuous phase containing a surfactant, a second solvent that is totally or partially immiscible with the first solvent, and sufficient first solvent to saturate the continuous phase; and (3) an extraction phase that is a nonsolvent for the polymer, a solvent for the continuous phase components, and a solvent for the first solvent, wherein the continuous phase solvent has solubility in the extraction phase of between about 0.1% and 25% by weight. Then, the dispersed phase and the continuous phase are mixed to form an emulsion, and the emulsion is then briefly mixed with a suitable quantity of extraction phase to induce skin formation at the interface of the dispersed and continuous phases. Remaining solvent is removed by an evaporation process step. The emulsification and solvent removal steps are preferably conducted in a continuous process. The brief extraction step prior to evaporation minimizes the loss of active agent from the microparticles, and reduces the required volume of extraction phase as compared to other extraction-based processes. Alternate emulsification methods, such as nonstatic mixers or emulsion lag tube, and solvent removal methods, such as incremental extraction, cryogenic extraction, or membrane separation, also are provided, and can be used in various combinations to make microparticles.

A composition, comprising an agent, a carrier admixed with the agent to form a mixture, and a film-forming polymer coating around the mixture which is insoluble in a selected solvent. A biocidal composition, comprising a biocide, such as an aldehyde, a carrier admixed with the aldehyde to form a mixture, and a film-forming polymer coating around the mixture which is insoluble in a selected solvent. The composition of the invention further comprising an acidifying agent admixed with the aldehyde. The composition of the invention and an activator. An article of manufacture, comprising the composition of the invention contained inside a fluid-permeable mesh bag. A method of making a biocidal composition, comprising admixing a carrier with an aldehyde to form a mixture, and coating the mixture with a film-forming polymer coating which is insoluble in a selected solvent. A method of making a biocidal article of manufacture, comprising enclosing within a fluid-permeable mesh bag the biocidal composition of the invention and an activator. A method of making a biocidal composition, comprising contacting the biocidal composition of the invention with the selected solvent and adding an activator to the composition in the solvent.

Encapsulated biocidal preparation

A composition for the controlled release of substances is provided that includes: (i) a non-polymeric, non-water soluble liquid carrier material (HVLCM) of viscosity of at least 5,000 cP at 37.degree. C. that does not crystallize neat under ambient or physiological conditions; and (ii) a substance to be delivered.

High viscosity liquid controlled delivery system

An antiphlogistic, analgesic, antipyretic parenteral preparation is disclosed comprising diclofenac, its salt, or both, a surfactant, cosurfactant, water, having a pH of 3-10, and optionally comprising an oily component, that can exhibit sustained therapeutic levels of diclofenac in plasma.

Growing community of inventors

Birmingham, AL, United States of America

Richard J Holl