Small volume oral transmucosal dosage forms containing sufentanil for treatment of pain

• US 8,226,978 B2
• Filed: 12/28/2007
• Issued: 07/24/2012
• 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, Hamel, Larry, Poutiatine, Andrew I., Rampersaud, Charles, Edwards, Bruce
• Primary Examiner(s): BARHAM, BETHANY P
• Application Number:
  US12/521,949
• Publication Number:
  US 20100105735A1
• Time in Patent Office: 1,670 Days
• Field of Search: None
• US Class Current: 424/464
• 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. A dosage form for oral transmucosal administration to a subject, comprising:

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

(i) said bioadhesive material provides for adherence of 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; and

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

2. The drug dosage form according to claim 1, 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.

3. The dosage form according to claim 1, wherein said dosage form has a mass of less than 10 mg or a volume of less than 10 μ

l.

4. The dosage form according to claim 1, wherein said oral transmucosal administration is sublingual or buccal administration.

5. The dosage form according to claim 1, 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.

6. The drug dosage form according to claim 4, wherein said dosage form delivers at least 60% of the total amount of sufentanil in said dosage form via the sublingual route.

7. The drug dosage form according to claim 4, wherein a single sublingual administration of said dosage form to a subject results in a bioavailability of greater than 50%.

8. The dosage form according to claim 4, wherein a single sublingual administration of said dosage form to a subject results in a bioavailability of greater than 60%.

9. The dosage form according to claim 4, wherein a single sublingual administration of said dosage form to a subject results in a bioavailability of greater than 70%.

10. The drug dosage form according to claim 4, wherein following repeated sublingual administrations of said dosage form to a subject, the bioavailability is greater than the bioavailability following a single sublingual administration to said subject.

11. The drug dosage form according to claim 4, wherein the difference between the T_max following repeated sublingual administrations and the time of the previous sublingual administration is shorter than the T_max following a single sublingual administration to said subject.

12. The formulation according to claim 1, wherein said dosage form is selected from the group consisting of a lozenge, a pill, a tablet, a membrane and a strip.

13. The dosage form according to claim 12, wherein said dosage form is a tablet.

14. A single dose applicator (SDA), comprising a dosage form according to claim 1.

15. A method of treating pain, comprising administering the dosage form of claim 1 to a patient in need thereof using a single dose applicator (SDA).

16. The method according to claim 15, wherein said pain is acute pain, breakthrough pain or post-operative pain.

17. The method according to claim 16, wherein said pain is acute inpatient pain.

18. The method according to claim 16, wherein said pain is post-operative pain.