Dow Global Technolgoies LLC

University of Minnesota

Rohm and Haas Company

Steven J Guillaudeu

Nicholas S Grasman

Meinolf Brackhagen

Robert L Schmitt

Oliver Petermann

Matthias Knarr

Roland Adden

Robert L Sammler

Michael J Mullins

Frank Steven Bates

Marc Andrew Hillmyer

Matthias Sprehe

True L Rogers

Mark B Wilson

Theresa M Reineke

Li Guo

Stephanie L Potisek

Ashwin R Bharadwaj

Jeffrey M Ting

Uma Shrestha

Wesley J Spaulding

Lakmini Widanapathirana

Maureen L Rose

William W Porter, Iii

Kevin P O'donnell

Ligeng Yin

Swapnil Tale

Oliver Peterman

A liquid composition which comprises an organic liquid diluent and at least one non-ionic cellulose ether having a viscosity of up to 2.33 mPa&#xb7;s, measured as a 2 wt.-% solution in water at 20&#xb0; C., is stable over an extended time period. The liquid composition is useful for preparing a solid dispersion comprising at least one active ingredient in at least one cellulose ether by spray-drying. Alternatively a solid dispersion can be produced by blending and extruding at least one active ingredient, at least one cellulose ether having a viscosity of up to 2.33 mPa&#xb7;s and optionally one or more adjuvants.

Composition comprising an organic liquid diluent and a cellulose ether of very low viscosity

The present invention relates to the use of uncrosslinked copolymers having a backbone comprising i) a plurality of thermo-responsive structural units derived from one or more than one N-alkyl or N,N-dialkyl substituted (alkyl)acrylamide monomer and ii) a plurality of hydrophilic structural units derived from one or more than one second ethylenically unsaturated monomer as excipients in solid mixtures with poorly water-soluble substances for effective solubilization of the latter in aqueous media. Solid dosage forms comprising a solid mixture of such copolymer(s) and poorly water-soluble substance(s) are also within the scope of the invention.

Copolymers as excipients for effective solubilization of poorly water-soluble substances from solid mixtures

A solid dispersion comprising at least one active ingredient in at least one hydroxyalkyl methylcellulose having a DS of from 1.0 to 2.7 and an MS of from 0.40 to 1.30, wherein DS is the degree of substitution of methoxyl groups and MS is the molar substitution of hydroxyalkoxyl groups, can be produced by extrusion or spray-drying.

Solid dispersion comprising a highly substituted hydroxyalkyl methylcellulose

Esterified cellulose ethers comprising groups of formula &#x2014;C(O)&#x2014;CHR'&#x2014;CHR&#x2033;&#x2014;COOA, wherein, R&#x2032; and R&#x2033; are hydrogen or (&#x2014;S)m(&#x2014;R)n-R, wherein Ris a hydrocarbon group having 1 to 4 carbon atoms, Ris an optionally substituted 5- or 6-membered cyclic group, m and n each independently are 0 or 1, and A is hydrogen or a cation, with the proviso that in each group CHR&#x2032;&#x2014;CHR&#x2033; one of R&#x2032; and R&#x2033; is hydrogen and the other one is (&#x2014;S)m(&#x2014;R)n-R, are useful as excipients for maintaining the concentration of poorly water-soluble drugs in aqueous liquids at supersaturation levels.

Cellulose ethers esterified with dicarboxylic acid

A liquid composition comprises an organic diluent and at least one cellulose ether having anhydroglucose units joined by 1-4 linkages and having methyl groups, hydroxyalkyl groups, and optionally alkyl groups being different from methyl as substituents such that hydroxyl groups of anhydroglucose units are substituted with methyl groups such that s23/s26 is 0.29 or less, wherein s23 is the molar fraction of anhydroglucose units wherein only the two hydroxyl groups in the 2- and 3-positions of the anhydroglucose unit are substituted with a methyl group and wherein s26 is the molar fraction of anhydroglucose units wherein only the two hydroxyl groups in the 2- and 6-positions of the anhydroglucose unit are substituted with a methyl group. The liquid composition can be used for preparing a solid dispersion of an active ingredient in a cellulose ether.

Composition comprising an organic diluent and a cellulose ether

Esterified cellulose ethers which comprise (i) aliphatic monovalent acyl groups or (ii) groups of the formula &#x2014;C(O)&#x2014;R&#x2014;COOA, wherein R is a divalent aliphatic or aromatic hydrocarbon group and A is hydrogen or a cation, or (iii) a combination of aliphatic monovalent acyl groups and groups of the formula &#x2014;C(O)&#x2014;R&#x2014;COOA, which have a viscosity of up to 2.33 mPa&#xb7;s, measured as a 2.0 wt % solution of the esterified cellulose ether in 0.43 wt % aqueous NaOH at 20&#xb0; C., and which have a viscosity of up to 13 mPao&#xb7;s, measured as a 10 wt % solution of the esterified cellulose ether in acetone at 20&#xb0; C. are useful for preparing solid dispersions comprising drugs.

Esterified cellulose ethers of low viscosity

An esterified cellulose ether comprises (i) aliphatic monovalent acyl groups or (ii) groups of the formula &#x2014;C(O)&#x2014;R&#x2014;COOA wherein R is a divalent aliphatic or aromatic hydrocarbon group and A is hydrogen or a cation or (iii) a combination of aliphatic monovalent acyl groups and groups of the formula &#x2014;C(O)&#x2014;R&#x2014;COOA, wherein the cellulose ether has anhydroglucose units joined by 1-4 linkages and has methyl groups, hydroxyalkyl groups, and optionally alkyl groups being different from methyl as substituents such that the esterified cellulose ether has an MS (hydroxyalkyl) of 0.05 to 1.00, and hydroxyl groups of anhydroglucose units are substituted with methyl groups such that [s23/s26&#x2212;0.2*MS(hydroxyalkyl)] is 0.36 or less, wherein s23 is the molar fraction of anhydroglucose units wherein only the two hydroxyl groups in the 2- and 3-positions of the anhydroglucose unit are substituted with a methyl group and wherein s26 is the molar fraction of anhydroglucose units wherein only the two hydroxyl groups in the 2- and 6-positions of the anhydroglucose unit are substituted with a methyl group. The esterified cellulose ether is useful as an excipient for poorly water-soluble drugs.

Esterified cellulose ethers having a specific substituent distribution

A multifunctional aromatic amine hardener composition including the reaction condensation product of (a) at least one aniline and (b) at least one non-aromatic cyclic dicarboxaldehyde; and a reactive thermosettable resin composition including (i) at least one multifunctional aromatic amine hardener composition curing agent, (ii) at least one thermoset resin, and optionally (c) at least one catalyst; and a process for preparing a thermoset product from the thermosettable composition. The hardener composition above and a thermoset resin may be used to prepare a thermoset product with improved thermo-mechanical behavior.

Hardeners for thermosettable resin compositions

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Midland, MI, United States of America

Steven J Guillaudeu