Bioadhesive drug formulations for oral transmucosal delivery

• US 20080166404A1
• Filed: 07/03/2007
• Published: 07/10/2008
• Est. Priority Date: 01/05/2007
• 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 8,252,329 B2
• Time in Patent Office: Days
• US Class Current: 424/451
• CPC Class Codes: A61J 3/005 Coating of tablets or the like coating of sweetmeats or confectionery A23G3/20; coating of granules in general B01J2/006
• CPC Class Codes: A61J 7/00 Devices for administering medicines orally, e.g. spoons calibrated capacity measures for fluids or fluent solid material G01F19/00; weighing spoons G01G19/56; Pill counting devices; Arrangements for time indication or reminder for taking medicine
• CPC Class Codes: A61J 7/0023 Spoons
• CPC Class Codes: A61J 7/0046 Cups, bottles or bags
• CPC Class Codes: A61J 7/0053 Syringes, pipettes or oral dispensers
• CPC Class Codes: A61K 31/4468 having a nitrogen directly attached in position 4, e.g. clebopride, fentanyl
• 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 9/2072 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: A61P 25/00 Drugs for disorders of the nervous system

Abstract

Bioadhesive drug formulations that adhere to an oral mucosal membrane of a subject are provided together with single dose applicators and devices for delivering the drug formulations to the oral mucosa, and methods for using the same.

Claims

1-92. -92. (canceled)

93. A bioadhesive formulation for sublingual administration to a subject as a solid dosage form, comprising:

(a) a non-ordered mixture of a pharmaceutically active amount of a drug;

(b) a bioadhesive material, said bioadhesive material providing for adherence to the oral mucosa of said subject; and

(c) stearic acid.

94. A dosage form comprising the bioadhesive formulation according to claim 93, wherein said dosage form comprises from about 1 μ

g to 10 mg of said pharmaceutically active drug.

95. The dosage form according to according to claim 93, wherein said dosage form is a tablet.

96. The drug dosage form according to claim 95, wherein said dosage form becomes a hydrogel upon contact with an aqueous fluid.

97. The drug dosage form according to claim 95, wherein said dosage form is an eroding dosage form wherein upon contact with an aqueous fluid, the surface of the dosage form hydrates and erodes, without formation of a hydrogel.

98. The drug dosage form according to claim 95, wherein upon contact with an aqueous fluid said dosage form disintegrates and forms a film.

99. The drug dosage form according to claim 94, wherein dissolution of said dosage form is independent of pH.

100. The dosage form according to according to claim 99, wherein dissolution of said dosage form is independent of pH over a pH range of about 4 to 8.

108. A single-dose applicator comprising, a bioadhesive drug dosage form according to claim 94.

110. A device comprising a dosage form according to a claim 94.

112. A method of placing a bioadhesive dosage form on a sublingual membrane of a subject, comprising:

(a) obtaining a bioadhesive dosage form according to claim 94; and

(b) placing said bioadhesive dosage form on said sublingual membrane, wherein said dosage form adheres to said membrane.

113. The method according to claim 112, wherein said placing is effected without a device.

114. The method according to claim 112, wherein said placing is effected using a device.

115. The method according to claim 112, wherein said device is a single dose applicator.

116. A method of treating pain in a subject, comprising, administering a bioadhesive dosage form according to claim 94 to said subject, wherein following said administration, pain relief is evident in said subject.

117. The method of claim 116, wherein said pain is acute pain, breakthrough pain or post-operative pain.

101. A bioadhesive formulation for sublingual administration to a subject as a solid dosage form, comprising:

(a) a non-ordered mixture of a pharmaceutically active amount of a drug;

(b) a bioadhesive material, said bioadhesive material providing for adherence to the oral mucosa of said subject, wherein dissolution of said drug formulation is independent of pH over a pH range of about 4to 8.

102. A dosage form comprising the bioadhesive formulation according to claim 101, wherein said composition comprises from about 1 μ

g to 10 mg of said pharmaceutically active drug.

103. The dosage form according to claim 101, wherein said formulation further comprises stearic acid.

104. The dosage form according to claim 101, wherein said formulation further comprises a non-ordered mixture of microparticles.

105. The dosage form according to claim 101, wherein said dosage form is selected from the group consisting of a lozenge, a pill, a tablet, a membrane and a strip.

106. The dosage form according to according to claim 105, wherein said dosage form is a tablet.

107. The drug dosage form according to claim 106, wherein upon contact with an aqueous fluid said dosage form disintegrates and forms a film.

109. A single dose applicator comprising, a bioadhesive drug dosage form according to claim 102.

111. A device comprising a dosage form according to a claim 102.