Dow Global Technolgoies LLC

Nicholas S Grasman

Meinolf Brackhagen

Steven J Guillaudeu

Oliver Petermann

Robert L Schmitt

Roland Adden

Matthias Knarr

Robert L Sammler

Matthias Sprehe

True L Rogers

Juergen Hermanns

Yvonne M Goerlach-Doht

Jorg Theuerkauf

Sjoerd A De Vries

Yongfu Li

David M Meunier

Uma Shrestha

Wesley J Spaulding

Maureen L Rose

William W Porter, Iii

Kevin P O'donnell

Jennifer L'hote-Gaston

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

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

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

A partially cross-linked esterified cellulose ether having A) groups of the formula &#x2014;C(O)&#x2014;R&#x2014;COOA or a combination of aliphatic monovalent acyl groups and 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, and B) having a molecular weight distribution such that [Wf(&#x3e;100 k)&#x2212;Wf(&#x3e;100 k)XL]/Wf(&#x3e;100 k)XL is at least 0.20, wherein Wf(&#x3e;100 k) is the total weight fraction of the esterified cellulose ether that exceeds 100,000 g/mol, and Wf(&#x3e;100 k)XL is the weight fraction that exceeds 100,000 g/mol of the methylated esterified cellulose ether is useful as enteric polymer for pharmaceutical dosage forms.

Partially cross-linked esterified cellulose ethers

A method of controlling or adjusting release of an active ingredient from a dosage form comprising the active ingredient and a polysaccharide derivative has been found. The method comprises the steps of

Method of controlling the release of an active ingredient from a dosage form

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

A melt-extruded polymer composition comprising a) at least one cellulose ether, b) one or more active ingredients and c) one or more optional additives, wherein said at least one cellulose ether has an MS (hydroxyalkyl) of 0.05 to 0.55 and hydroxyl groups of anhydroglucose units are substituted with methyl groups such that [s23/s26&#x2212;0.2*MS(hydroxyalkyl)] is 0.32 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.

Melt-extruded composition comprising a cellulose ether

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

Polysaccharide derivatives having a median Equivalent Projected Circle Diameter (EQPC) of less than 140 micrometers and a particle size and shape distribution meeting condition A or B or both are useful for preparing dosage forms, particularly for preparing compressed sustained-release dosage forms: A. non-compacted polysaccharide derivative particles have a flowability of at least 45 g/sec through a vertically inverted cone having a vertex angle of about 40 and an outlet diameter of about 50 mm, or B. i) no more than 40 volume percent of the polysaccharide derivative particles are fine particles having a particle length LEFI of less than 40 micrometers and ii) no more than 40 volume percent of the polysaccharide derivative particles are fibrous particles, and the sum of the fine particles and the fibrous particles does not exceed 50 volume percent.

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Midland, MI, United States of America

Nicholas S Grasman