SMALL VOLUME ORAL TRANSMUCOSAL DOSAGE FORMS CONTAINING SUFENTANIL FOR TREATMENT OF PAIN

• US 20130158074A1
• Filed: 07/23/2012
• Published: 06/20/2013
• Est. Priority Date: 01/06/2006
• Status: Active Grant

• Current Assignee: Vertical Pharmaceuticals LLC (Vertical/Trigen Holdings LLC)
• Original Assignee: AcelRx Pharmaceuticals Incorporated
• Inventors: Palmer, Pamela, Schreck, Thomas, Tzannis, Stelios, Rampersaud, Charles, Edwards, Bruce, Hamel, Larry, Poutiatine, Andrew I.
• Granted Patent: US 8,778,393 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

Compositions, methods and systems for administration of small volume sufentanil-containing drug dosage forms to the oral mucosa of a subject are disclosed.

Claims

1-63. -63. (canceled)

64. A method of treating pain in a subject, comprising administering a dosage form to the oral mucosa of a subject, wherein said dosage form comprises:

from about 5 to about 100 micrograms (mcg) of sufentanil, and a bioadhesive material, wherein;

(i) said bioadhesive material adheres the dosage form to the oral mucosa of said subject during the period of drug delivery;

(ii) said dosage form has a volume of less than 30 microliters or a mass of less than 30 mg; and

(iii) after administration of said dosage form to said subject, said dosage form provides a minimal saliva response and minimal swallowing of sufentanil;

at least 55% of drug delivery of sufentanil occurs via the oral transmucosal route;

said dosage form provides a dose-normalized mean C_max of 1.59-2.75 pg/mL per mcg dosed;

said dosage form provides a T_max of from about 19.8 minutes to about 60 minutes; and

said dosage form provides a T_max with a coefficient of variation of less than 40%.

65. The method according to claim 64, wherein said dosage form comprises a dose of sufentanil selected from the group consisting of 5 mcg, 10 mcg, 15 mcg, 20 mcg, 30 mcg, 40 mcg, 50 mcg, 60 mcg, 70 mcg, 80 mcg and 100 mcg.

66. The method according to claim 64, wherein said dosage form has a mass of less than 10 mg or a volume of less than 10 μ

l.

67. The method according to claim 64, wherein said oral transmucosal administration is sublingual or buccal administration.

68. The method according to claim 64, wherein said dosage form has an erosion time of from 30 seconds up to a time selected from the group consisting of 5 minutes, 10 minutes, 15 minutes and 30 minutes.

69. The method according to claim 67, wherein said dosage form delivers at least 60% of the total amount of sufentanil in said dosage form via the sublingual route.

70. The method according to claim 67, wherein a single sublingual administration of said dosage form to a subject results in a bioavailability of sufentanil of greater than 50%.

71. The method according to claim 67, wherein a single sublingual administration of said dosage form to a subject results in a bioavailability of sufentanil of greater than 60%.

72. The method according to claim 67, wherein a single sublingual administration of said dosage form to a subject results in a bioavailability of sufentanil of greater than 70%.

73. The method according to claim 67, wherein the bioavailability of sufentanil following repeated sublingual administrations of said dosage form to a subject, is greater than the bioavailability of sufentanil following a single sublingual administration to said subject.

74. The method according to claim 64, wherein said dosage form is selected from the group consisting of a lozenge, a pill, a tablet, a membrane and a strip.

75. The method according to claim 74, wherein said dosage form is a tablet.

76. The method according to claim 64, wherein said pain is acute pain, breakthrough pain or post-operative pain.

77. The method according to claim 76, wherein said pain is acute inpatient pain.

78. The method according to claim 76, wherein said pain is post-operative pain.