Abstract: A compound comprised of a hydrophilic polymer covalently yet reversibly linked to a amine-containing ligand through a dithiobenzyl linkage is described.

Abstract: A composition for administration of a therapeutically effective dose of a topoisomerase inhibitor I or topoisomerase I/II inhibitor is described. The composition includes liposomes having an outer surface and an inner surface defining an aqueous liposome compartment, and being composed of a vesicle-forming lipid and of a vesicle-forming lipid derivatized with a hydrophilic polymer to form a coating of hydrophilic polymer chains on both the inner and outer surfaces of the liposomes. Entrapped in the liposomes is the topoisomerase inhibitor at a concentration of at least about 0.10 ?mole drug per ?mole lipid.

Abstract: Conjugates of a hydrophobic moiety, such as a lipid, linked through a cleavable dithiobenzyl linkage to a therapeutic agent are described. The dithiobenzyl linkage is susceptible to cleavage by mild thiolysis, resulting in release of the therapeutic agent in its original form. The linkage is stable under nonreducing conditions. The conjugate can be incorporated into liposomes for administration in vivo and release of the therapeutic agent in response to endogeneous in vivo reducing conditions or in response to administration of an exogeneous reducing agent.

Abstract: The present invention provides a multi-release oral drug delivery system that initiates drug release following an initial drug-free release interval, after administration to a subject, and a second drug-free release period before release of another dose of drug. The system has (1) inner compartments enclosed within a semipermeable membrane, and (2) a drug coating on the exterior of the semipermeable membrane surrounded by a microporous membrane, which microporous membrane is permeable to fluid and drug. The drug coating is released after the initial drug-free release interval. An inner compartment drug is released after a second drug-free release interval provided by a drug-free inner compartment.

Abstract: An osmotic delivery system having a space-efficient piston is provided. The enclosure has an interior holding the piston, a protein or polypeptide, and an osmotic agent. The piston is movable with respect to an interior surface of the capsule, and defines a movable seal with the interior surface of the capsule. The movable seal separates the osmopolymer from the protein or peptide. The piston has a recess that receives at least a portion of the osmotic agent. The osmotic agent imbibes liquid from a surrounding environment to cause the piston to move and in turn cause delivery of the beneficial agent from the capsule.

Abstract: This invention relates to stable non-aqueous single phase viscous vehicles and to formulations utilizing such vehicles. The formulations comprise at least one beneficial agent uniformly suspended in the vehicle. The formulation is capable of being stored at temperatures ranging from cold to body temperature for long periods of time. The formulations are capable of being uniformly delivered from drug delivery systems at an exit shear rate of between about 1 to 1×10?7 reciprocal second.

Abstract: A dosage form that facilitates the controlled release of an active agent at a desired release rate or release rate profile includes a bi-layer membrane system and an osmotic core. The bi-layer membrane system includes a semipermeable membrane and an osmosensitive membrane and forms an internal compartment occupied by the osmotic core. The osmotic core includes an active agent composition and a light push layer. A passageway is formed through the bi-layer membrane system and permits expulsion of the active agent composition from the dosage form during operation. The bi-layer membrane system and the osmotic core are formulated and formed to provide controlled release of the active agent included in the active agent composition, while simultaneously facilitating increased loading of active agent within a dosage form of given dimension and increasing the delivery efficiency of such active agent relative to prior osmotic dosage forms including a push layer.

Abstract: Compositions of and methods for formulating and delivering biologically active agent formulations having enhanced physical stability, and wherein deterioration from the presence of oxygen and/or water is minimized and/or controlled, to yield a stable formulation. The compositions of and methods for formulating and delivering biologically active agents of the present invention further facilitate their incorporation into a biocompatible coating which can be employed to coat a stratum-corneum piercing microprojection, or a plurality of stratum-corneum piercing microprojections of a delivery device, for delivery of the biocompatible coating through the skin of a subject, thus providing an effective means of delivering the biologically active agents.

Abstract: A composition includes a viscous gel formed from a combination of a biodegradable polymer and a biocompatible solvent. The composition also includes a hydrophilic porogen, which may be incorporated in the viscous gel. The composition may form a porous scaffold in situ.

Abstract: A composition for administration of a therapeutically effective dose of a topoisomerase inhibitor I or topoisomerase I/II inhibitor is described. The composition includes liposomes having an outer surface and an inner surface defining an aqueous liposome compartment, and being composed of a vesicle-forming lipid and of a vesicle-forming lipid derivatized with a hydrophilic polymer to form a coating of hydrophilic polymer chains on both the inner and outer surfaces of the liposomes. Entrapped in the liposomes is the topoisomerase inhibitor at a concentration of at least about 0.10 ?mole drug per ?mole lipid.

Abstract: In one aspect, the present invention is directed to an osmotic pump that automatically provides an ascending release rate of active agent as the osmotic pump functions in an environment of operation and may be designed for implantation within a desired animal or human subject. An osmotic pump according to the present invention includes a reservoir, a rate controlling membrane, an expandable osmotic composition, an active agent formulation and an exit orifice. Once administered to an environment of operation, water passes through the rate controlling membrane and into the osmotic composition, which causes the osmotic composition to expand and expel the active agent formulation through the exit orifice at a rate that is directly proportional to the rate at which water passes through the rate controlling membrane.

Abstract: A conjugate comprised of a hydrophilic polymer covalently yet reversibly linked to a amine-, hydroxy- or carboxyl-containing ligand is described. The resulting conjugate is capable of releasing the parent amine, hydroxy, or carboxyl-containing compound via thiol-mediated cleavage. The system allows for delivery of various amino-, hydroxy-, or carboxy-containing drugs in the form of their thiolytically cleavable macromolecular conjugates.

Abstract: The present invention provides methods and devices for the electrotransport delivery of beneficial agents that utilize polymer electrolyte matrices as drug reservoirs. In certain aspects of the invention, the beneficial agents are hydrolytically unstable, and methods are provided for enhancing the stability of the hydrolytically unstable beneficial agents during long-term storage of devices for the electrotransport delivery of the hydrolytically unstable beneficial agents and during electrotransport delivery of the hydrolytically unstable beneficial agents.

Abstract: An osmotic delivery system having a space-efficient piston is provided. The enclosure has an interior holding the piston, a protein or peptide, and an osmotic agent. The piston is movable with respect to an interior surface of the capsule, and defines a movable seal with the interior surface of the capsule. The movable seal separates the osmopolymer from the protein or peptide. The piston has a recess that receives at least a portion of the osmotic agent. The osmotic agent imbibes liquid from a surrounding environment to cause the piston to move and, in turn, cause delivery of the beneficial agent from the capsule.

Abstract: A membrane system comprising an interior wall, a fluid-permeable exterior wall surrounding the interior wall and an internal compartment defined by the membrane system, wherein fluid permeability of the interior wall is responsive to osmolarity of an osmotic core within the internal compartment are disclosed. A controlled release dosage form comprising the membrane system and a process for delivering an osmotically active formulation from an osmotic pump over an extended period of time are also disclosed.

Abstract: An electrotransport agent delivery device (10) for delivering a therapeutic agent through intact skin, and a method of operating same, is provided. The device applies a pulsing electrotransport current wherein current pulses have a magnitude above a critical level (Ic) at which the skin is transformed into a higher electrotransport delivery efficiency (E) state. Most preferably the length of the applied current pulses is at least 5 msec and preferably at least 10 msec.

Abstract: The present invention includes an osmotic pump that includes a means for venting an osmotic composition included in the pump before the internal pressure of the pump has the opportunity to build to such an extent that the pump is structurally compromised, such as when one or more components of the pump are physically separated. The means for venting osmotic material included in an osmotic pump according to the present invention includes a vent that allows the material included in the osmotic composition of the pump to dissipate into an environment of operation at a rate that results in dissipation of the pressure created within the osmotic pump and a reduced potential for subject discomfort or irritation.

Abstract: An injectable depot formulation includes a biocompatible polymer, an organic solvent combined with the biocompatible polymer to form a viscous gel, and a small molecule drug incorporated in the viscous gel such that the formulation exhibits an in vivo release profile having Cmax to Cmin ratio less than 200 and lag time less than 0.2.

Abstract: A sustained release dosage form includes a capsule made of a thermoplastic polymer having a softening point below 200° C. and an orifice formed or formable within the capsule, an emulsion formulation contained within the capsule, and an expandable composition within the capsule remote from the orifice. The emulsion formulation comprises a drug, an emulsifying surfactant, and an oil. The expandable composition is configured to expand and expel the emulsion formulation through the orifice.

Abstract: A diffusional drug delivery device is described which can provide for stability of the adhesive and system components, elimination of the initial burst of drug and hence irritation, and to provide for delayed onset of therapeutic effect along with delivery of a therapeutic agent at an optimum rate. The therapeutic agent in a first form which is suitable for storage, and the anhydrous activating means are inert when in an anhydrous environment. Moisture activates the system whereby the activating means provides an acidic or basic solution and the first form of the therapeutic agent is converted to a second form which is suitable for absorption through the skin or mucosa.