Merck + Co., Inc.

Allergan, Inc.

University of Nebraska

Kenneth J Himmelstein

Gaylen M Zentner

Gerald S Rork

David Frederick Woodward

Takeru Higuchi

Stefano A Pogany

Gyorgy F Ambrus

Shulin Ding

Abhay Joshi

Nienyuan J Chang

Cara L Baustian

Cheryl Ringeisen

Reversibly gel-forming compositions for sustained delivery of bio-affecting substances are disclosed. The compositions exhibit significant changes in viscosity in response to changes in pH. The compositions contain relatively low concentrations of a stable combination of at least one pH-responsive gelling polymer and at least one other thermally nonresponsive polymer. The compositions are preferably formulated to include one or more therapeutic or diagnostic agents for administration as a liquid that will gel in situ or for topical application as a pre-formed gel.

Reversible gel-forming composition for sustained delivery of

Sustained release pharmaceutical compound delivery compositions and methods for their production are disclosed wherein ion exchange resin particles are loaded with releasably bound pharmaceutical compounds and incorporated in an aqueous reversibly gelling polymeric solution. The pores of the ion exchange resin are sufficiently small to lock in the pharmaceutical compound without exposure to the large polymer molecules. The pharmaceutical compound remains bound within the pores of the ion exchange resin particles until after administration to a target tissue site where small ions migrate into the pores and initiate an exchange reaction.

Compositions for controlled delivery of pharmaceutical compounds

Pharmaceutical compositions are disclosed which effectively treat the symptoms of hypersensitivity diseases without irritation. The pharmaceutical compositions are complexes of at least one leukotriene receptor antagonist and at least one antihistamine. The complexes can be formulated in low viscosity solutions for administering to an individual as an aerosol or drops or through intravenous, subcutaneous, or intramuscular injection. Alternatively, the complexes can be formulated in high viscosity creams for topical delivery to the skin or ocular environment.

Leukotriene receptor antagonist and antihistamine complex pharmaceutical

Reversibly gelling aqueous compositions are disclosed which undergo significant changes in viscosity in response to substantially simultaneous changes in both temperature and pH. The compositions are formed of relatively low concentrations of a stable combination of at least one pH-sensitive reversibly gelling polymer and at least one temperature-sensitive reversibly gelling polymer. The compositions can be formulated to exhibit a sol-gel transition over a wide range of conditions and viscosities and may be modified to incorporate a pharmaceutical compound for utilization as droppable or injectable drug delivery systems which will gel following administration to a physiological system for the sustained delivery of such pharmaceutical compounds.

Reversible gelation compositions and methods of use

The instant invention is directed to an osmotic pump comprising: (A) at least one active agent surrounded by (B) a rate controlling water insoluble wall, having a fluid permeability of 6.96.times.10.sup.-18 to 6.96.times.10.sup.-14 cm.sup.3 sec/g and a reflection coefficient of less than 1, prepared from:

Controlled porosity osmotic pump

The instant invention is directed to a multiparticulate osmotic pump, for the controlled release of a pharmaceutically active agent to an environment of use, said pump comprising:

Multiparticulate controlled porosity osmotic

The invention relates to the use of carboxylic acids incorporated as a catalyst in poly(orthoester)s and other acid labile polymers such that upon exposure to aqueous environments the acid catalyzes the erosion of the polymer matrix. The rate of release of a drug substance incorporated into or surrounded by the poly(orthoester) or other acid labile polymer can be controlled in that the drug is released as the polymer is eroded in response to the catalytic action of the acid incorporated therein.

Organic acids as catalysts for the erosion of polymers

The invention relates to the use of an acid anhydride incorporated as a latentiated catalyst in poly(ortho ester) and other polymers such that upon exposure to aqueous environments the acid anhydride generates the corresponding acid which catalyzes the matrix erosion. The releasing rate of a loaded drug substance incorporated into or surrounded by the poly(ortho ester) or other polymers can be controlled in that the drug is released as the poly(ortho ester)s or other polymer is eroded by action of the acid anhydride incorporated therein.

Acid anhydrides as rate controlling agent for the erosion of polymers

An osmotic drug (or other beneficial substance) delivery system comprises a compartment with one or more chambers in series formed by an external shell and chamber-dividing walls of a microporous material and successive overlayers of semipermeable membranes completely covering the outer shell of all but one chamber and substantially covering the outer shell of that one chamber, each successive overlayer completely covering all but one more chamber and substantially covering that one more chamber. Osmotic agents, adjuvants, enzymes, drugs, pro-drugs, pesticides and the like are incorporated in the chambers covered by the semipermeable membranes, and external fluids that diffuse into that chamber form solutions and by osmotic pressure are forced through the microporous chamber-dividing wall to the drug or drug-forming chamber to form a solution thereof and then through the exposed microporous shell to the exterior of the device at a rate controlled by the permeability of the semipermeable overlay and the osmotic pressure gradient across the shell.

Growing community of inventors

Irvine, CA, United States of America

Kenneth J Himmelstein