PHARMACEUTICAL COMPOSITIONS

• US 20140030322A1
• Filed: 09/25/2013
• Published: 01/30/2014
• Est. Priority Date: 01/09/2008
• Status: Active Grant

• Current Assignee: LOCL Pharma, Inc. (Charleston Laboratories, Inc.)
• Original Assignee: Charleston Laboratories, Inc.
• Inventors: Bosse, Paul, Ameling, John, Schachtel, Bernard, Takigiku, Ray
• Granted Patent: US 9,226,901 B2
• Time in Patent Office: Days
• US Class Current: 424/456
• CPC Class Codes: A61K 31/165 having aromatic rings, e.g. colchicine, atenolol, progabide
• CPC Class Codes: A61K 31/167 having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
• CPC Class Codes: A61K 31/24 having an amino or nitro group
• CPC Class Codes: A61K 31/403 condensed with carbocyclic rings, e.g. carbazole
• CPC Class Codes: A61K 31/404 Indoles, e.g. pindolol
• CPC Class Codes: A61K 31/4196 1,2,4-Triazoles
• CPC Class Codes: A61K 31/422 not condensed and containing further heterocyclic rings
• CPC Class Codes: A61K 31/437 the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
• CPC Class Codes: A61K 31/454 containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• CPC Class Codes: A61K 31/515 Barbituric acids; Derivatives thereof, e.g. sodium pentobarbital
• CPC Class Codes: A61K 31/522 having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
• CPC Class Codes: A61K 31/5415 ortho- or peri-condensed with carbocyclic ring systems, e.g. phenothiazine, chlorpromazine, piroxicam
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 47/36 Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
• CPC Class Codes: A61K 9/0024 Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L
• CPC Class Codes: A61K 9/0056 Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
• CPC Class Codes: A61K 9/1694 resulting in granules or microspheres of the matrix type containing more than 5% of excipient
• CPC Class Codes: A61K 9/2013 Organic compounds, e.g. phospholipids, fats
• 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 9/2086 : Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat active cores with a complete drug-free outer coat A61K9/28
• CPC Class Codes: A61K 9/209 : containing drug in at least two layers or in the core and in at least one outer layer
• CPC Class Codes: A61K 9/4808 : characterised by the form of the capsule or the structure of the filling; Capsules containing small tablets; Capsules with outer layer for immediate drug release capsules filled with granules or microparticles A61K9/16; filled with microcapsules or coated microparticles A61K9/50; with mixture of different granules, microcapsules, (coated) microparticles A61K9/5084
• CPC Class Codes: A61K 9/5084 : Mixtures of one or more drugs in different galenical forms, at least one of which being granules, microcapsules or (coated) microparticles according to A61K9/16 or A61K9/50, e.g. for obtaining a specific release pattern or for combining different drugs tablets containing such a mixture A61K9/2077
• CPC Class Codes: A61P 1/08 : for nausea, cinetosis or vertigo; Antiemetics
• CPC Class Codes: A61P 25/04 : Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/06 : Antimigraine agents
• CPC Class Codes: A61P 25/08 : Antiepileptics; Anticonvulsants
• 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 29/02 : without antiinflammatory effect
• CPC Class Codes: A61P 39/00 : General protective or antinoxious agents
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/02 : Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system

Abstract

Methods and compositions are provided which comprise effective amounts of analgesic to treat a subject, including reducing or eliminating an adverse effect associated with the analgesic.

Claims

1-138. -138. (canceled)

139. A solid composition comprising:

a. an effective amount of;

i. one or more opioid analgesics, and

ii. one or more antiemetics; and

b. a pharmaceutically acceptable carrier or vehicle.

140. The solid composition of claim 139, wherein:

the one or more opioid analgesics is hydrocodone, oxycodone, morphine, diamorphine, codeine, pethidine, alfentanil, buprenorphine, butorphanol, dezocine, fentanyl, hydromorphone, levomethadyl acetate, levorphanol, meperidine, methadone, morphine sulfate, nalbuphine, oxycodone, oxymorphone, pentazocine, propoxyphene, remifentanil, sufentanil, tramadol, or a pharmaceutically acceptable salt of each of the foregoing.

141. The solid composition of claim 139, wherein:

the one or more antiemetics is aprepitant, dronabinol, perphenazine, palonosetron, trimethyobenzamide, metoclopromide, domperidone, prochlorperazine, promethazine, chlorpromazine, trimethobenzamide, ondansetron, granisetron, hydroxyzine, acetylleucine monoethanolamine, alizapride, azasetron, benzquinamide, bietanautine, bromopride, buclizine, clebopride, cyclizine, dimenhydrinate, diphenidol, dolasetron, meclizine, methallatal, metopimazine, nabilone, oxyperndyl, pipamazine, scopolamine, sulpiride, tetrahydrocannabinol, thiethylperazine, thioproperazine, tropisetron, droperidol, haloperidol, prochloperazine, metoclopramide, diphenhydramine, cannabis, midazolam, lorazepam, hyoscine, dexamethasone, emetrol, propofol, or a pharmaceutically acceptable salt of each of the forgoing.

142. The solid composition of claim 139, wherein the one or more antiemetics comprise promethazine or a pharmaceutically acceptable salt thereof.

143. The solid composition of claim 139, wherein the one or more opioid analgesics comprise hydrocodone or a pharmaceutically acceptable salt thereof or oxycodone or a pharmaceutically acceptable salt thereof, and the one or more antiemetics comprise promethazine or a pharmaceutically acceptable salt thereof and ondansetron or a pharmaceutically acceptable salt thereof.

144. The solid composition of claim 143, wherein the one or more opioid analgesics comprise from about 6.5 mg to about 8.5 mg of the hydrocodone or a pharmaceutically acceptable salt thereof and the one or more antiemetics comprise from about 11 mg to about 14 mg of the promethazine or a pharmaceutically acceptable salt thereof.

145. The solid composition of claim 139, further comprising one or more non-opioid analgesics.

146. The solid composition of claim 145, wherein the one or more non-opioid analgesics is acetaminophen, ibuprofen, carprofen, fenbuprofen, flubiprofen, ketaprofen, ketorolac, loxoprofen, naproxen, suprofen, or a pharmaceutically acceptable salt of each of the forgoing.

147. The solid composition of claim 145, wherein the one or more non-opioid analgesics are present in an amount of about 200 mg to about 600 mg.

148. The solid composition of claim 139, comprising two or more of the antiemetics.

149. The solid composition of claim 148, wherein the two or more of the antiemetics comprise:

promethazine or a pharmaceutically acceptable salt thereof and ondansetron or a pharmaceutically acceptable salt thereof.

150. The solid composition of claim 139, wherein the solid composition is an oral dosage form comprising:

a. a controlled-release layer comprising the one or more opioid analgesics; and

b. an immediate-release layer comprising the one or more antiemetics.

151. The solid composition of claim 139, further comprising a stimulant.

152. The solid composition of claim 151, wherein the stimulant is aminophylline, caffeine, dyphlline, oxitriphylline, theophhylline, amphetamine, benzphetamine, dextroamphetamine, diethylpropion, mazindol, methamphetamine, methylphenidate, dexmethylphenidate, pemoline, sibutramine, modafinil, atomoxetine, phendimetrizine, phenteramine, adrafinil, phenylpropanolamine, psuedoephedrine, synephrine, amphetaminil, furfenorex, or a pharmaceutically acceptable salt of each of the forgoing.

153. The solid composition of claim 139, further comprising a barbiturate agent.

154. The solid composition of claim 153, wherein the barbiturate agent is allobarbital, alphenal, amobarbital, aprobarbital, barbexaclone, barbital, brallobarbital, butabarbital, butalbital, butobarbital, butallylonal, crotylbarbital, cyclobarbital, cyclopal, ethallobarbital, febarbamate, heptabarbital, hexethal, hexobarbital, mephobarbital, metharbital, methohexital, methylphenobarbital, narcobarbital, nealbarbital, pentobarbital, primidone, probarbital, propallylonal, proxibarbal, proxibarbital, reposal, secbutabarbital, secobarbital, sigmodal, talbutal, thialbarbital, thiamylal, thiobarbital, thiobutabarbital, thiopental, valofane, vinbarbital, vinylbital, 1,3-dimethoxymethyl 5,5-diphenyl-barbituric acid, 1-monomethoxymethyl 5,5-diphenylbarbituric acid diphenyl-barbituric acid, or a pharmaceutically acceptable salt of each of the forgoing.

155. The solid composition of claim 139, further comprising an opioid antagonist or an abuse deterrent agent.

156. The solid composition of claim 155, wherein the opioid antagonist agent or abuse deterrent agent comprises nalmefene, naloxone, naltrexone, cyclazacine, levallorphan, niacin, or a pharmaceutically acceptable salt of each of the forgoing.

157. The solid composition of claim 155, wherein the abuse deterrent agent is formulated as a gel-forming agent comprising a pharmaceutically acceptable polymer.

158. The solid composition of claim 157, wherein the pharmaceutically acceptable polymer is capable of forming a viscous gel upon contact with a solvent, wherein the viscous gel resists crushing and snorting.

159. The solid composition of claim 157, wherein the pharmaceutically acceptable polymer is selected from the group consisting of polyethylene oxide, polyvinyl alcohol, hydroxypropyl methyl cellulose, carbomers, and combinations thereof.

160. The solid composition of claim 139, wherein the solid composition is formulated as a tablet, capsule, particulate, or a combination thereof.

161. The solid composition of claim 160, wherein the tablet is a multi-layer tablet.

162. The solid composition of claim 160, wherein the tablet is a bi-layer tablet.

163. The solid composition of claim 160, wherein the tablet is an enteric-coated tablet.

164. The solid composition of claim 139, wherein the solid composition further comprises one or more excipients of:

carnauba wax, crospovidone, diacetylated monoglycerides, ethylcellulose, hydroxypropyl cellulose, hypromellose phthalate, hypromellose, magnesium stearate, mannitol, sodium hydroxide, sodium stearyl fumarate, talc, titanium dioxide, glyceryl monostearate 40-50, methacrylic acid copolymer type C, polysorbate 80, sugar spheres, triethyl citrate, and yellow ferric oxide.

165. The solid composition of claim 160, wherein the solid composition is formulated as a particulate.

166. The solid composition of claim 165, wherein the particulate is a bead, a sphere or a pellet.

167. The solid composition of claim 165, wherein the particulate is controlled-release coated.

168. The solid composition of claim 165, wherein the particulate is enteric-coated.

169. The solid composition of claim 160, wherein the solid composition is formulated as a particulate incorporated into a capsule.

170. The solid composition of claim 169, wherein the capsule is a soft gelatin capsule or a hard gelatin capsule.

171. The solid composition of claim 169, wherein the capsule comprises an inner dosage component and an outer dosage component, the latter being in the form of an envelope over the former.

172. The solid composition of claim 171, wherein the inner dosage and outer dosage components are separated by an enteric layer.

173. The solid composition of claim 169, wherein the capsule has micro drilled holes.