Emisphere Technologies, Inc.

Novartis Ag

Cytec Technology Corporation

Hoffmann-la Roche Inc.

F. Hoffmann-la Roche Ag

William Elliott Bay

Shingai Majuru

JoAnne P Corvino

Steven Minh Dinh

Nikhil Dhoot

Doris C O'Toole

Moise Azria

Simon David Bateman

Michael M Goldberg

Rajesh K Agarwal

Joseph Ault

Joseph Sikora

Kiran Chaudhary

Subash Patel

Rebecca F Yang

Joseph Zielinski

Yi Ren

Jun Liao

Halina Levchik

Puchun Liu

Pingsheng Zhang

Joseph Norman Bernadino

Moses O Oyewumi

George Frederick Klein

Matthew A Brown

David R Kilanowski

The present invention relates to crystalline polymorphic forms of the di-sodium salt of N-(5-chlorosalicyloyl)-8-aminocaprylic acid, pharmaceutical compositions containing the same, methods of preparing the same, and methods for facilitating the delivery of active agents with the same.

Crystalline forms of the di-sodium salt of N-(5-chlorosalicyloyl)-8-aminocaprylic acid

Oral insulin formulations and processes for preparing oral insulin formulations are provided.

Formulations for delivering insulin

The inventors have discovered that the disodium salt of certain delivery agents has surprisingly greater efficacy for delivering active agents than the corresponding monosodium salt. Furthermore, the inventors have discovered that the disodium salts of these delivery agents form solvates with ethanol and hydrates with water. Preferred delivery agents include, but are not limited to, N-(5-chlorosalicyloyl)-8-aminocaprylic acid (5-CNAC), N-(10-[2-hydroxybenzoyl]amino)decanoic acid (SNAD), and sodium N-(8-[2-hydroxybenzoyl]amino)caprylate (SNAC). The invention also provides methods of preparing the disodium salt, ethanol solvate, and hydrate and compositions containing the disodium salt, ethanol solvate, and/or hydrate.

Disodium salts, monohydrates, and ethanol solvates for delivering active agents

Crystalline forms of the di-sodium salt of N-(5-Chlorosalicyloyl)-8-aminocaprylic acid

The inventors have discovered that the disodium salt of certain delivery agents has surprisingly greater efficacy for delivering active agents than the corresponding monosodium salt. Furthermore, the inventors have discovered that the disodium salts of these delivery agents form solvates with ethanol and hydrates with water. The delivery agents have the formula wherein

Disclosed are improved methods for the synthesis of N-(8-[2-hydroxybenzoyl]-amino)caprylic acid. Certain compounds have been found useful for preventing the formation of a colored impurity when included in an ester hydrolysis reaction. Conducting ester hydrolysis in anaerobic conditions has also been found to minimize the formation of the color impurity. Also disclosed are improved methods for synthesizing the sodium salt of N-(8-[2-hydroxybenzoyl]-amino)caprylic acid.

Methods for producing N-(8-[2-hydroxybenzoyl]-amino) caprylic acid

A process is disclosed for preparing acid amides, including isocyanate-functional 1,3,5-triazines and isocyanate-based 1,3,5 triazine derivatives, from the reaction of (Si, Ge or Sn substituted amino)-1,3,5 triazines and acid halides.

Process for preparing acid amides from (Si, Ge, or Sn substituted amino)-1,3,5-triazines and acid halides

Provided is a process for preparing chloroalkyl pyridinium hydrochloride compounds and various regioisomers and analogs thereof having substantially high purity levels and yields and a free-flowing, non-dusting form.

Chloroalkyl pyridinium hydrochloride compounds and processes for their

Growing community of inventors

Ridgefield, CT, United States of America

William Elliott Bay