PHARMACEUTICAL COMPOSITION AND ADMINISTRATIONS THEREOF

• US 20170087144A1
• Filed: 08/31/2016
• Published: 03/30/2017
• Est. Priority Date: 08/13/2008
• Status: Active Grant

• Current Assignee: Vertex Pharmaceuticals Incorporated
• Original Assignee: Vertex Pharmaceuticals Incorporated
• Inventors: ROWE, WIlliam, HURTER, Patricia, YOUNG, Christopher, DINEHART, Kirk, VERWIJS, Marinus Jacobus, OVERHOFF, Kirk, BOTFIELD, Martyn, GROSSI, Alfredo, GROOTENHUIS, Peter D.J.
• Granted Patent: US 10,646,481 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/44 Non condensed pyridines; Hydrogenated derivatives thereof
• CPC Class Codes: A61K 31/47 Quinolines; Isoquinolines
• CPC Class Codes: A61K 9/0053 Mouth and digestive tract, i.e. intraoral and peroral administration rectal administration A61K9/0031
• CPC Class Codes: A61K 9/1635 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/1652 Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin homeopathic globules A61K9/1623
• CPC Class Codes: A61K 9/2009 Inorganic compounds
• CPC Class Codes: A61K 9/2013 Organic compounds, e.g. phospholipids, fats
• CPC Class Codes: A61K 9/2018 Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
• CPC Class Codes: A61K 9/2027 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/28 Dragees; Coated pills or tablets , e.g. with film or compression coating A61K9/2072 takes precedence, e.g. partially coated tablets A61K9/2072, coated multilayer tablets A61K9/2086, tablets with drug-coated core A61K9/209
• CPC Class Codes: A61K 9/282 Organic compounds, e.g. fats
• CPC Class Codes: A61K 9/284 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/08 Bronchodilators
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 19/08 for bone diseases, e.g. rachitism, Paget's disease
• CPC Class Codes: A61P 19/10 for osteoporosis
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/00 : Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

The present invention relates to pharmaceutical compositions comprising a solid dispersion of N-[2,4-Bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide, methods of manufacturing pharmaceutical compositions of the present invention, and methods of administering pharmaceutical compositions of the present invention.

Claims

1-111. -111. (canceled)

112. A pharmaceutical tablet comprising 34.1% of a solid dispersion by weight of the tablet, wherein the solid dispersion comprises 80% of a mixture of amorphous N-[2,4-Bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide (Compound 1) and less than 15% crystalline Compound 1 by weight of the dispersion, 19.5% of HPMCAS by weight of the dispersion, and 0.5% SLS by weight of the dispersion.

113. The pharmaceutical tablet of claim 112, wherein the tablet further comprises 30.5% of microcrystalline cellulose by weight of the tablet.

114. The pharmaceutical tablet of claim 112, wherein the tablet further comprises 30.4% of lactose by weight of the tablet.

115. The pharmaceutical tablet of claim 112, wherein the tablet further comprises 3% of sodium croscarmellose by weight of the tablet.

116. The pharmaceutical tablet of claim 112, wherein the tablet further comprises 0.5% of SLS by weight of the tablet.

117. The pharmaceutical tablet of claim 112, wherein the tablet further comprises 0.5% of colloidal silicon dioxide by weight of the tablet.

118. The pharmaceutical tablet of claim 112, wherein the tablet further comprises 1.0% of magnesium stearate by weight of the tablet.

119. The pharmaceutical tablet of claim 112, wherein the tablet further comprises a coating.

120. The pharmaceutical tablet of claim 112, wherein the tablet has a hardness of 98 N (10 kp)±

20 percent.

121. The pharmaceutical tablet of claim 112, wherein the tablet contains 150 mg of Compound 1.

122. The pharmaceutical tablet of claim 112, wherein the tablet contains 100 mg of Compound 1.

123. A method of treating or lessening the severity of cystic fibrosis in a patient in need thereof, comprising administering to the patient the pharmaceutical tablet of claim 112.

124. The method of claim 123, wherein said patient has a cystic fibrosis transmembrane conductance regulator (CFTR) protein with a Δ

F508 amino acid deletion.

125. The method of claim 123, wherein said patient has a cystic fibrosis transmembrane conductance regulator (CFTR) protein with a R117H amino acid substitution.

126. The method of claim 123, wherein said patient has a cystic fibrosis transmembrane conductance regulator (CFTR) protein with a G551 D amino acid substitution.

127. The method of claim 123, wherein the tablet is orally administered to the patient once per day.

128. The method of claim 123, wherein the tablet is orally administered every 12 hours.

129. The method of claim 123, wherein the tablet is orally administered concurrently with a high fat, high calorie CF meal or snack.

130. The method of claim 123, wherein the tablet is orally administered 30 minutes after administering a high fat, high calorie CF meal or snack.

131. The method of claim 123, wherein the tablet is administered concurrently with, prior to, or subsequent to an additional therapeutic agent.