Small-volume oral transmucosal dosage

• US 20090131479A1
• Filed: 10/11/2007
• Published: 05/21/2009
• Est. Priority Date: 01/06/2006
• Status: Active Grant

• Current Assignee: Vertical Pharmaceuticals LLC (Vertical/Trigen Holdings LLC)
• Original Assignee: AcelRx Pharmaceuticals Incorporated
• Inventors: Tzannis, Stelios, Schreck, Thomas, Hamel, Larry, Palmer, Pamela, Poutiatine, Andrew I.
• Granted Patent: US 8,231,900 B2
• Time in Patent Office: Days
• US Class Current: 514/326
• CPC Class Codes: A61J 2200/30 Compliance analysis for taking medication
• CPC Class Codes: A61J 7/0038 Straws
• CPC Class Codes: A61J 7/0053 Syringes, pipettes or oral dispensers
• CPC Class Codes: A61J 7/0418 with electronic history memory
• CPC Class Codes: A61J 7/0445 for preventing drug dispensing during a predetermined time period
• CPC Class Codes: A61J 7/0481 working on a schedule basis
• CPC Class Codes: A61K 31/4535 containing a heterocyclic ring having sulfur as a ring hetero atom, e.g. pizotifen
• CPC Class Codes: A61K 9/006 Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
• CPC Class Codes: A61K 9/20 Pills, tablets, discs, rods A61K9/0004, A61K9/0007, A61K9/0056, A61K9/0065 take precedence; for reconstitution of a drink A61K9/0095
• CPC Class Codes: A61K 9/2009 Inorganic compounds
• CPC Class Codes: A61K 9/2018 Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
• CPC Class Codes: A61K 9/2031 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers
• CPC Class Codes: A61K 9/2072 characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms A61K9/0004, A61K9/0056, A61K9/0065 take precedence
• CPC Class Codes: A61M 15/00 Inhalators drug delivery in endotracheal tubes A61M16/04
• CPC Class Codes: A61M 15/008 Electronic counters
• CPC Class Codes: A61M 15/0081 Locking means
• CPC Class Codes: A61M 15/0083 Timers
• CPC Class Codes: A61M 2205/276 preventing unwanted use
• CPC Class Codes: A61M 2205/3561 local, e.g. within room or hospital
• CPC Class Codes: A61M 2205/3584 using modem, internet or bluetooth
• CPC Class Codes: A61M 2205/3592 : using telemetric means, e.g. radio or optical transmission
• CPC Class Codes: A61M 2205/52 : with memories providing a history of measured variating parameters of apparatus or patient
• CPC Class Codes: A61M 2205/583 : by visual feedback
• CPC Class Codes: A61M 2205/6054 : Magnetic identification systems
• CPC Class Codes: A61M 2205/609 : Biometric patient identification means
• CPC Class Codes: A61M 2209/086 : Docking stations
• CPC Class Codes: A61P 25/00 : Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/04 : Centrally acting analgesics, e.g. opioids
• 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: G07C 9/22 : in combination with an identity check of the pass holder
• CPC Class Codes: G07F 17/0092 : for assembling and dispensing of pharmaceutical articles medical dispensers for private use, A61J7/00
• CPC Class Codes: H01Q 1/2208 : associated with components used in interrogation type services, i.e. in systems for information exchange between an interrogator/reader and a tag/transponder, e.g. in Radio Frequency Identification [RFID] systems methods or arrangements for sensing record carriers, e.g. for reading patterns G06K7/00; record carrier for use with machines and with at least a part designed to carry digital markings G06K19/00

Abstract

Small-volume oral transmucosal dosage forms or NanoTabs® comprising a predetermined amount of a pharmaceutically active drug are provided. Exemplary applications include use of the NanoTabs® to administer a drug for the treatment of acute, post-operative or breakthrough pain.

Claims

1-170. -170. (canceled)

171. A small volume dosage form for oral transmucosal administration to a subject, comprising:

(a) a pharmaceutically active amount of a drug; and

(b) a bioadhesive material, wherein said bioadhesive material provides for adherence to the oral mucosa of said subject and said dosage form has a mass of less than 30 mg or a volume of less than 30 μ

l.

172. The dosage form according to claim 171, wherein said dosage form has a mass of less than 10 mg or a volume of less than 10 μ

l.

173. The dosage form according to claim 171, wherein said oral transmucosal administration is sublingual administration.

174. The dosage form according to claim 171, wherein said oral transmucosal administration is buccal administration.

175. The dosage form according to claim 171, wherein said dosage form comprises from about 1 microgram to 50 mg of said pharmaceutically active drug.

176. The dosage form according to claim 175, comprising from about 1 microgram to 10 mg of said pharmaceutically active drug.

177. The dosage form according to claim 176, wherein said pharmaceutically active drug is an opioid selected from the group consisting of sufentanil, alfentanil, fentanyl, lofentanil, carfentanil, remifentanil, trefentanil, and mirfentanil.

178. The dosage form according to claim 177, comprising from about 0.25 micrograms to 200 micrograms of sufentanil.

179. The dosage form according to claim 178, comprising from about 2.5 micrograms to 100 micrograms of sufentanil.

180. The dosage form according to claim 179, wherein said dosage form comprises a dose of sufentanil selected from the group consisting of 5 micrograms (mcg), 10 mcg, 15 mcg, 20 mcg, 30 mcg, 40 mcg, 50 mcg, 60 mcg, 70 mcg and 80 mcg.

181. The dosage form according to claim 171, wherein the erosion time of said dosage form is from 30 seconds up to a time selected from the group consisting of 5 minutes, 10 minutes, 15 minutes and 30 minutes.

182. The dosage form according to claim 180, wherein a single oral transmucosal administration of said dosage form to a subject results in a bioavailability of greater than 65%.

183. The dosage form according to claim 180, wherein a single oral transmucosal administration of said dosage form to a subject results in a bioavailability of greater than 75%.

184. The dosage form according to claim 180, wherein a single oral transmucosal administration of said dosage form to a subject results in a bioavailability of greater than 85%.

185. The dosage form according to claim 171, wherein an amount of drug selected from the group consisting of at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98% and at least 99% of the total amount of drug in said dosage form is absorbed via the oral transmucosal route.

186. The dosage form according to claim 185, wherein at least 60% of the total amount of drug in said dosage form is absorbed via the oral transmucosal route.

191. The dosage form according to claim 171, wherein said dosage form is administered using a device.

192. A method of treating pain in a subject, comprising, administering a dosage form according to claim 177 to said subject, wherein following said administration, pain relief is evident in said subject.

193. The method of claim 192, wherein said pain is acute pain, breakthrough pain or post-operative pain.

187. A small volume dosage form for oral transmucosal administration to a subject, comprising:

from about 10 mcg to 10 mg of alfentanil and a bioadhesive material, wherein said bioadhesive material provides for adherence to the oral mucosa of said subject and said dosage form has a mass of less than 30 mg or a volume of less than 30 μ

l.

188. The dosage form according to claim 187, wherein said dosage form has a mass of less than 10 mg or a volume of less than 10 μ

l.

189. The dosage form according to claim 187, wherein said oral transmucosal administration is sublingual administration.

190. The dosage form according to claim 187, wherein said oral transmucosal administration is buccal administration.

194. A method of treating pain in a subject, comprising, administering a dosage form according to claim 187 to said subject, wherein following said administration, pain relief is evident in said subject.

195. The method of claim 194, wherein said pain is acute pain, breakthrough pain or post-operative pain.