Small-volume oral transmucosal dosage

• US 8,231,900 B2
• Filed: 10/11/2007
• Issued: 07/31/2012
• 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.
• Primary Examiner(s): Barham, Bethany
• Application Number:
  US11/974,092
• Publication Number:
  US 20090131479A1
• Time in Patent Office: 1,755 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

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 single dose of sufentanil, provided as a small volume solid tablet for oral transmucosal administration to a subject, comprising:

from about 0.25 micrograms (mcg) to 200 micrograms sufentanil, wherein;

a) said solid tablet is bioadhesive and adheres to the oral mucosa of said subject,

b) said solid tablet is a substantially homogeneous composition and has a volume of less than 30 microliters (mcl); and

wherein complete erosion of said solid tablet is evident by visual examination only after a time selected from the group consisting of about 5 minutes, about 10 minutes and about 15 minutes; and

c) after administration of said solid tablet to said subject, said solid tablet 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 solid tablet provides a T_max of from about 19.8 minutes to about 60 minutes; and

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

2. The bioadhesive solid tablet according to claim 1, wherein said solid tablet has a volume of less than 10 mcl.

3. The bioadhesive solid tablet according to claim 1, wherein said oral transmucosal administration is sublingual administration.

4. The bioadhesive solid tablet according to claim 1, wherein said oral transmucosal administration is buccal administration.

5. The bioadhesive solid tablet according to claim 1, comprising from about 2.5 micrograms to 100 micrograms of sufentanil.

6. The bioadhesive solid tablet according to claim 5, wherein said solid tablet comprises a dose of sufentanil selected from the group consisting of 5 micrograms, 10 mcg, 15 mcg, 20 mcg, 30 mcg, 40 mcg, 50 mcg, 60 mcg, 70 mcg, 80 mcg and 100 mcg.

7. The bioadhesive solid tablet according to claim 1, wherein the erosion time of said solid tablet is about 10 minutes.

8. The bioadhesive solid tablet according to claim 6, wherein a single oral transmucosal administration of said solid tablet to a subject results in a bioavailability of greater than 65%.

9. The bioadhesive solid tablet according to claim 6, wherein a single oral transmucosal administration of said solid tablet to a subject results in a bioavailability of greater than 75%.

10. The bioadhesive solid tablet according to claim 6, wherein a single oral transmucosal administration of said solid tablet to a subject results in a bioavailability of greater than 85%.

11. The bioadhesive solid tablet according to claim 1, wherein at least 55% of the total amount of drug in said solid tablet is absorbed via the oral transmucosal route.

12. The bioadhesive solid tablet according to claim 11, wherein at least 60% of the total amount of drug in said solid tablet is absorbed via the oral transmucosal route.

13. A drug delivery device comprising the bioadhesive solid tablet according to claim 1.

14. A bioadhesive solid tablet according to claim 1, wherein when subjected to an in vitro dissolution test in a Type II USP dissolution apparatus, at least 75% of the total amount of sufentanil in said solid tablet is released within 10 minutes.

15. A drug delivery device comprising the bioadhesive solid tablet according to claim 14.

16. A bioadhesive solid tablet according to claim 1, wherein sufentanil is provided as sufentanil citrate.