Small-volume oral transmucosal dosage forms

• US 10,342,762 B2
• Filed: 06/05/2014
• Issued: 07/09/2019
• 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, Lawrence, Poutiatine, Andrew I.
• Primary Examiner(s): Tran, Susan T
• Application Number:
  US14/296,992
• Publication Number:
  US 20140350054A1
• Time in Patent Office: 1,860 Days
• Field of Search: None
• 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. A dosage form for oral transmucosal administration to a subject, comprising:

from about 0.25 micrograms to about 200 micrograms sufentanil, wherein said dosage form is bioadhesive and has a volume of less than 30 microliters or a mass of less than 30 mg wherein after administration of the dosage form to the subject, the dosage form provides a Tmax with a coefficient of variation less than 40%, wherein said Tmax is from about 19.8 minutes to about 60 minutes.

2. The dosage form of claim 1, wherein the dosage form has a volume of less than 10 microliters or a mass of less than 10 mg.

3. The dosage form of claim 1, wherein after administration of the dosage form to the subject, at least 50% of the drug delivery of sufentanil occurs via the oral transmucosal route.

4. The dosage form of claim 3, wherein after administration of the dosage form to the subject, at least 55% of the drug delivery of sufentanil occurs via the oral transmucosal route.

5. The dosage form of claim 3, wherein after administration of the dosage form to the subject, at least 60% of the drug delivery of sufentanil occurs via the oral transmucosal route.

6. The dosage form of claim 1, wherein after administration of the dosage form to the subject results in a dose-normalized Cmax of about 2.72+/−

0.84 pg/mL per mcg dosed.

7. The dosage form of claim 1, wherein the oral transmucosal administration is to the sublingual membrane.

8. The dosage form of claim 1, wherein the administration is to the buccal membrane.

9. The dosage form of claim 1, wherein a single oral transmucosal administration of the dosage form to the subject results in a bioavailability of greater than 65%.

10. The dosage form of claim 1, wherein a single oral transmucosal administration of the dosage form to the subject results in a bioavailability of greater than 75%.

11. The dosage form of claim 1, wherein a single oral transmucosal administration of the dosage form to the subject results in a bioavailability of greater than 80%.

12. The dosage form of claim 1, wherein the dosage form comprises one or more hydrogel forming excipients.

13. The dosage form of claim 12, wherein the one or more hydrogel forming excipients is hydroxypropyl methylcellulose.

14. A drug delivery device comprising the dosage form of claim 1.

15. A dosage form for oral transmucosal administration to a subject, comprising:

a bioadhesive dosage form of from about 0.25 micrograms to about 200 micrograms sufentanil with a volume of less than 30 microliters or a mass of less than 30 mg wherein the administration of the dosage form to the subject results in a dose-normalized C_max of 2.72+/−

0.84 pg/mL per mcg of sufentanil dosed and a T_max with a coefficient of variation less than 40%.

16. The dosage form of claim 15, wherein after administration of the dosage form to the subject, the dosage form provides a T_max of from 19.8 minutes to 60 minutes.