Bioadhesive drug formulations for oral transmucosal delivery

• US 20070207207A1
• Filed: 01/05/2007
• Published: 09/06/2007
• Est. Priority Date: 01/06/2006
• 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
• Granted Patent: US 8,252,328 B2
• Time in Patent Office: Days
• US Class Current: 424/464
• 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: 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 25/04 Centrally acting analgesics, e.g. opioids

Abstract

Formulations for controlled delivery of oral transmucosal medications are provided. The formulations are characterized as hydrogel-forming or eroding-types which are bioadhesive and provide for controlled and sustained release of the medication such that enhanced bioavailability and efficacy is provided.

Claims

1. A bioadhesive drug dosage form for oral transmucosal administration comprising a dissolvable drug formulation wherein said formulation contains a predetermined amount of a pharmaceutically active opioid selected from the group consisting of sufentanil, alfentanil, fentanyl, lofentanil, carfentanil, remifentanil, trefentanil, and mirfentanil, and a bioadhesive material, said bioadhesive material providing for adherence to the oral mucosal membrane of a subject.

2. The bioadhesive drug dosage form according to claim 1, wherein said oral mucosal membrane is a sublingual membrane.

3. The bioadhesive drug dosage form according to claim 1, wherein said oral mucosal membrane is a buccal membrane.

4. The bioadhesive drug dosage form according to claim 2, wherein said dosage form becomes a hydrogel and swells upon contact with an aqueous fluid.

5. The bioadhesive drug dosage form according to claim 2, 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.

8. The bioadhesive drug dosage form according to claim 1, wherein said dosage form has a mucoadhesive strength of greater than 500 dynes/cm².

11. The bioadhesive drug dosage form according to claim 1, wherein said dosage form has an erosion time of from 30 seconds up to a time selected from the group consisting of 1 minute, 2 minutes, 3 minutes, 4 minutes, 5 minutes, 10 minutes, 15 minutes, 30 minutes, 1 hour, 2 hours, 4 hours and 8 hours or longer.

14. The bioadhesive drug dosage form according to claim 1, wherein the amount of the drug in said dissolvable drug formulation absorbed via the oral mucosa is selected from the group consisting of at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98% and at least 99% of the drug in said dosage form.

17. The bioadhesive drug dosage form according to claim 1, wherein said dosage form comprises an amount of said pharmaceutically active opioid selected from the group consisting of 10 μ

g, 15 μ

g, 25 μ

g, 50 μ

g, 100 μ

g, 500 μ

g, 1 mg, 2mg, 3mg, 4 mg, 5 mg, 6 mg, 7 mg, 8 mg, 9 mg and 10 mg.

18. The bioadhesive drug dosage form according to claim 4, wherein said dosage form comprises an amount of said pharmaceutically active opioid selected from the group consisting of 10 μ

g, 15 μ

g, 25 μ

g, 50 μ

g, 100 μ

g, 500 μ

g, 1 mg, 2 mg, 3 mg, 4 mg, 5 mg, 6 mg, 7 mg, 8 mg, 9 mg and 10 mg.

22. The bioadhesive drug dosage form according to claim 1, comprising a pharmaceutically active amount of sufentanil.

25. The bioadhesive drug dosage form according to claim 22, comprising from about 0.25 μ

g to 200 micrograms (μ

g) of sufentanil.

28. The bioadhesive drug dosage form according to claim 22, comprising from about 2.5 μ

g to 100 μ

g of sufentanil.

31. The bioadhesive drug dosage form according to claim 22, comprising from about 0.02 μ

g to 5 micrograms per kilogram (μ

g/kg) of sufentanil.

34. The bioadhesive drug dosage form according to claim 22, comprising about 2 μ

g, 5 μ

g or 10 μ

g of sufentanil.

37. The bioadhesive drug dosage form according to claim 1, comprising from about 10 μ

g to 10 mg of alfentanil.

40. The bioadhesive drug dosage form according to claim 1, comprising from about 2 μ

g to 1500 μ

g of fentanyl.

43. The bioadhesive drug dosage form according to claim 1, comprising from about 50 μ

g to 1500 μ

g of fentanyl.

46. The bioadhesive drug dosage form according to claim 1, comprising from about 200 g to 1500 μ

g of fentanyl.

49. The bioadhesive drug dosage form according to claim 1, comprising from about 0.25 μ

g to 99.9 mg of lofentanil.

52. The bioadhesive drug dosage form according to claim 1, comprising from about 0.25 μ

g to 99.9 mg of carfentanil.

55. The bioadhesive drug dosage form according to claim 1, comprising from about 0.25 μ

g to 99.9 mg of remifentanil.

58. The bioadhesive drug dosage form according to claim 1, comprising from about 0.25 μ

g to 99.9 mg of trefentanil.

61. The bioadhesive drug dosage form according to claim 1, comprising from about 0.25 μ

g to 99.9 mg of mirfentanil.

64. The bioadhesive drug dosage form according to claim 1, wherein a single or repeated oral transmucosal administration to a subject results in a bioavailability of greater than 70%.

67. The bioadhesive drug dosage form according to claim 1, wherein a single or repeated oral transmucosal administration to a subject results in a bioavailability of greater than 75%.

70. The bioadhesive drug dosage form according to claim 1, wherein a single or repeated oral transmucosal administration to a subject results in a bioavailability of greater than 85%.

73. The bioadhesive drug dosage form according to claim 1, wherein a single or repeated oral transmucosal administration to a subject results in a bioavailability of greater than 90%.

76. The bioadhesive drug dosage form according to claim 1, wherein a single or repeated oral transmucosal administration to a subject results in a bioavailability of greater than 94%.

79. The bioadhesive drug dosage form according to claim 1, wherein a single or repeated oral transmucosal administration to a subject results in a bioavailability with a coefficient of variation of less than 30%.

82. The bioadhesive drug dosage form according to claim 1, wherein a single or repeated oral transmucosal administration to a subject results in a bioavailability with a coefficient of variation of less than 40%.

85. The dissolvable drug dosage form according to claim 1, wherein a single oral transmucosal administration of said drug dosage form to a subject results in a C_max with a coefficient of variation of less than 30%.

88. The dissolvable drug dosage form according to claim 1, wherein a single oral transmucosal administration of said drug dosage form to a subject results in a C_max with a coefficient of variation of less than 40%.

91. The dissolvable drug dosage form according to claim 1, wherein a single oral transmucosal administration of said drug dosage form to a subject results in a T_max of from about 5 minutes to about 2 hours.

94. The dissolvable drug dosage form according to claim 1, wherein a single oral transmucosal administration of said drug dosage form results in a plasma level that reaches 50% of C_max in a time selected from about 3 minutes to 2 hours, from about 3 minutes to 30 minutes, from about 3 minutes to 20 minutes and from about 3 minutes to 10 minutes.

97. The dissolvable drug dosage form according to claim 1, wherein a single oral transmucosal administration of said drug dosage form results in a plasma half-life of from about 5 minutes and about 6 hours.

100. The dissolvable drug dosage form according to claim 1, wherein a single oral transmucosal administration of said drug dosage form results in a therapeutic time ratio of greater than 0.07.

103. The dissolvable drug dosage form according to claim 1, wherein a single oral transmucosal administration of said drug dosage form results in a therapeutic time ratio of from about 0.5 to about 2.0.

106. The dissolvable drug dosage form according to claim 1, wherein said drug dosage form has a disintegration time of from about 30 seconds to about 30 minutes and oral transmucosal administration of said drug dosage form results in a time of onset (T_onset) of from about 3 minutes to about 23 or 30 minutes.

109. The dissolvable drug dosage form according to claim 1, wherein said drug dosage form has a disintegration time of from about 15 minutes to about 8 hours and oral transmucosal administration of said drug dosage form results in a time of onset (T_onset) of from about 14 minutes to about 82 minutes or from about 10 minutes to about 100 minutes.

112. The dissolvable drug dosage form according to claim 22, wherein said drug dosage form has a disintegration time of from about 30 seconds to about 30 minutes and oral transmucosal administration of said drug dosage form results in a time of onset (T_onset) of from about 3 minutes to about 13.5 or 15 minutes.

115. The dissolvable drug dosage form according to claim 22, wherein said drug dosage form has a disintegration time of from about 15 minutes to about 8 hours and oral transmucosal administration of said drug dosage form results in a time of onset (T_onset) of from about 14 minutes to about 82 minutes or from about 10 minutes to about 100 minutes.

118. The dissolvable drug dosage form according to claim 37, wherein said drug dosage form has a disintegration time of from about 30 seconds to about 30 minutes and oral transmucosal administration of said drug dosage form results in a time of onset (T_onset) of from about 10 minutes to about 30 minutes.

121. The dissolvable drug dosage form according to claim 1, wherein said drug dosage form has a disintegration time of from about 30 seconds to about 30 minutes and oral transmucosal administration of said drug dosage form results in a plasma half-life of from about 20 minutes and about 140 minutes.

124. The dissolvable drug dosage form according to claim 1, wherein said drug dosage form has a disintegration time of from about 15 minutes to about 8 hours and oral transmucosal administration of said drug dosage form results in a plasma half-life of from about 100 minutes and about 300 minutes.

127. The dissolvable drug dosage form according to claim 22, wherein said drug dosage form has a disintegration time of from about 30 seconds to about 30 minutes and oral transmucosal administration of said drug dosage form results in a plasma half-life of from about 27 minutes and about 71 minutes or form about 20 to about 80 minutes.

130. The dissolvable drug dosage form according to claim 22, wherein said drug dosage form has a disintegration time of from about 15 minutes to about 8 hours and oral transmucosal administration of said drug dosage form results in a plasma half-life of from about 112 minutes and about 298 minutes or from about 100 to about 300 minutes.

133. The dissolvable drug dosage form according to claim 37, wherein said drug dosage form has a disintegration time of from about 30 seconds to about 30 minutes and oral transmucosal administration of said drug dosage form results in a plasma half-life of from about 32 minutes and about 50 minutes or from about 25 to about 100 minutes.

136. The dissolvable drug dosage form according to claim 1, wherein said drug dosage form has a disintegration time of from about 30 seconds to about 30 minutes and oral transmucosal administration of said drug dosage form results in a therapeutic time ratio of from about 0.08 to about 0.48 or from about 0.05 to about 0.5.

139. The dissolvable drug dosage form according to claim 1, wherein said drug dosage form has a disintegration time of from about 15 minutes to about 8 hours and oral transmucosal administration of said drug dosage form results in a therapeutic time ratio of from about 0.34 to about 1.82 or from about 0.3 to about 2.0.

142. The dissolvable drug dosage form according to claim 22, wherein said drug dosage form has a disintegration time of from about 30 seconds to about 30 minutes and oral trans-mucosal administration of said drug dosage form results in a therapeutic time ratio of from about 0.12 to about 0.44 or from about 0.05 to about 0.5.

145. The dissolvable drug dosage form according to claim 22, wherein said drug dosage form has a disintegration time of from about 15 minutes to about 8 hours and oral transmucosal administration of said drug dosage form results in a therapeutic time ratio of from about 0.42 to about 1.82 or from about 0.4 to about 2.0.

148. The dissolvable drug dosage form according to claim 37, wherein said drug dosage form has a disintegration time of from about 30 seconds to about 30 minutes and oral transmucosal administration of said drug dosage form results in a therapeutic time ratio of from about 0.26 to about 0.4 or from about 0.1 to about 0.5.

151. A method of treating a subject exhibiting a symptomatic medical condition, comprising, administering the dissolvable drug dosage form according to claim 1, wherein said drug dosage form comprises a pharmaceutically active amount of a drug effective to reduce or eliminate said symptoms in the subject.

154. The method according to claim 103, wherein said symptomatic medical condition is pain.

157. A method of a treating pain in a subject comprising, administering a dissolvable drug dosage form according to claim 1, wherein said drug dosage form comprises a pharmaceutically active amount of a drug effective to reduce or eliminate symptoms of pain, wherein following administration of said drug dosage form symptoms of pain are reduced or eliminated in said subject.

6. A bioadhesive drug dosage form for oral transmucosal administration comprising a dissolvable drug formulation wherein said formulation contains a predetermined amount of a pharmaceutically active agent and a bioadhesive material, said bioadhesive material providing for adherence to the oral mucosal membrane of a subject and wherein said dosage form becomes a hydrogel and swells upon contact with an aqueous fluid.

9. The bioadhesive drug dosage form according to claim 6, wherein said dosage form has a mucoadhesive strength of greater than 500 dynes/cm².

12. The bioadhesive drug dosage form according to claim 6, wherein said dosage form has an erosion time of from 30 seconds up to a time selected from the group consisting of 1 minute, 2 minutes, 3 minutes, 4 minutes, 5 minutes, 10 minutes, 15 minutes, 30 minutes, 1 hour, 2 hours, 4 hours and 8 hours or longer.

15. The bioadhesive drug dosage form according to claim 6, wherein the amount of the drug in said dissolvable drug formulation absorbed via the oral mucosa is selected from the group consisting of at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98% and at least 99% of the drug in said dosage form.

19. The bioadhesive drug dosage form according to claim 6, wherein said dosage form comprises an amount of said pharmaceutically active agent selected from the group consisting of 10 μ

g, 15 μ

g, 25 μ

g, 50 μ

g, 100 μ

g, 500 μ

g, 1 mg, 2 mg, 3 mg, 4 mg, 5 mg, 6 mg, 7 mg, 8 mg, 9 mg and 10 mg.

20. The bioadhesive drug dosage form according to claim 6, wherein said pharmaceutically active agent is an opioid selected from the group consisting of sufentanil, alfentanil, fentanyl, lofentanil, carfentanil, remifentanil, trefentanil, and mirfentanil.

23. The bioadhesive drug dosage form according to claim 20, comprising a pharmaceutically active amount of sufentanil.

26. The bioadhesive drug dosage form according to claim 23, comprising from about 0.25 μ

g to 200 micrograms (μ

g) of sufentanil.

29. The bioadhesive drug dosage form according to claim 23, comprising from about 2.5 μ

g to 100 μ

g of sufentanil.

32. The bioadhesive drug dosage form according to claim 23, comprising from about 0.02 μ

g to 5 micrograms per kilogram (μ

g/kg) of sufentanil.

35. The bioadhesive drug dosage form according to claim 23, comprising about 2 μ

g, 5 μ

g or 10 μ

g of sufentanil.

38. The bioadhesive drug dosage form according to claim 20, comprising from about 10 μ

g to 10 mg of alfentanil.

41. The bioadhesive drug dosage form according to claim 20, comprising from about 2 μ

g to 1500 μ

g of fentanyl.

44. The bioadhesive drug dosage form according to claim 20, comprising from about 50 μ

g to 1500 μ

g of fentanyl.

47. The bioadhesive drug dosage form according to claim 20, comprising from about 200 μ

g to 1500 μ

g of fentanyl.

50. The bioadhesive drug dosage form according to claim 20, comprising from about 0.25 μ

g to 99.9 mg of lofentanil.

53. The bioadhesive drug dosage form according to claim 20, comprising from about 0.25 μ

g to 99.9 mg of carfentanil.

56. The bioadhesive drug dosage form according to claim 20, comprising from about 0.25 μ

g to 99.9 mg of remifentanil.

59. The bioadhesive drug dosage form according to claim 20, comprising from about 0.25 μ

g to 99.9 mg of trefentanil.

62. The bioadhesive drug dosage form according to claim 20, comprising from about 0.25 μ

g to 99.9 mg of mirfentanil.

65. The bioadhesive drug dosage form according to claim 20, wherein a single or repeated oral transmucosal administration to a subject results in a bioavailability of greater than 70%.

68. The bioadhesive drug dosage form according to claim 20, wherein a single or repeated oral transmucosal administration to a subject results in a bioavailability of greater than 75%.

71. The bioadhesive drug dosage form according to claim 20, wherein a single or repeated oral transmucosal administration to a subject results in a bioavailability of greater than 85%.

74. The bioadhesive drug dosage form according to claim 20, wherein a single or repeated oral transmucosal administration to a subject results in a bioavailability of greater than 90%.

77. The bioadhesive drug dosage form according to claim 20, wherein a single or repeated oral transmucosal administration to a subject results in a bioavailability of greater than 94%.

80. The bioadhesive drug dosage form according to claim 20, wherein a single or repeated oral transmucosal administration to a subject results in a bioavailability with a coefficient of variation of less than 30%.

83. The bioadhesive drug dosage form according to claim 20 wherein a single or repeated oral transmucosal administration to a subject results in a bioavailability with a coefficient of variation of less than 40%.

86. The dissolvable drug dosage form according to claim 20, wherein a single oral transmucosal administration of said drug dosage form to a subject results in a C_max with a coefficient of variation of less than 30%.

89. The dissolvable drug dosage form according to claim 20, wherein a single oral transmucosal administration of said drug dosage form to a subject results in a C_max with a coefficient of variation of less than 40%.

92. The dissolvable drug dosage form according to claim 20, wherein a single oral transmucosal administration of said drug dosage form to a subject results in a T_max of from about 5 minutes to about 2 hours.

95. The dissolvable drug dosage form according to claim 20, wherein a single oral transmucosal administration of said drug dosage form results in a plasma level that reaches 50% of C_max in a time selected from about 3 minutes to 2 hours, from about 3 minutes to 30 minutes, from about 3 minutes to 20 minutes and from about 3 minutes to 10 minutes.

98. The dissolvable drug dosage form according to claim 20, wherein a single oral transmucosal administration of said drug dosage form results in a plasma half-life of from about 5 minutes and about 6 hours.

101. The dissolvable drug dosage form according to claim 20, wherein a single oral transmucosal administration of said drug dosage form results in a therapeutic time ratio of greater than 0.07.

104. The dissolvable drug dosage form according to claim 20, wherein a single oral transmucosal administration of said drug dosage form results in a therapeutic time ratio of from about 0.5 to about 2.0.

107. The dissolvable drug dosage form according to claim 6, wherein said drug dosage form has a disintegration time of from about 30 seconds to about 30 minutes and oral transmucosal administration of said drug dosage form results in a time of onset (T_onset) of from about 3 minutes to about 23 or 30 minutes.

110. The dissolvable drug dosage form according to claim 6, wherein said drug dosage form has a disintegration time of from about 15 minutes to about 8 hours and oral transmucosal administration of said drug dosage form results in a time of onset (T_onset) of from about 14 minutes to about 82 minutes or from about 10 minutes to about 100 minutes.

113. The dissolvable drug dosage form according to claim 23, wherein said drug dosage form has a disintegration time of from about 30 seconds to about 30 minutes and oral transmucosal administration of said drug dosage form results in a time of onset (T_onset) of from about 3 minutes to about 13.5 or 15 minutes.

116. The dissolvable drug dosage form according to claim 23, wherein said drug dosage form has a disintegration time of from about 15 minutes to about 8 hours and oral transmucosal administration of said drug dosage form results in a time of onset (T_onset) of from about 14 minutes to about 82 minutes or from about 10 minutes to about 100 minutes.

119. The dissolvable drug dosage form according to, claim 38, wherein said drug dosage form has a disintegration time of from about 30 seconds to about 30 minutes and oral transmucosal administration of said drug dosage form results in a time of onset (T_onset) of from about 10 minutes to about 30 minutes.

122. The dissolvable drug dosage form according to claim 6, wherein said drug dosage form has a disintegration time of from about 30 seconds to about 30 minutes and oral transmucosal administration of said drug dosage form results in a plasma half-life of from about 20 minutes and about 140 minutes.

125. The dissolvable drug dosage form according to claim 6, wherein said drug dosage form has a disintegration time of from about 15 minutes to about 8 hours and oral transmucosal administration of said drug dosage form results in a plasma half-life of from about 100 minutes and about 300 minutes.

128. The dissolvable drug dosage form according to claim 23, wherein said drug dosage form has a disintegration time of from about 30 seconds to about 30 minutes and oral transmucosal administration of said drug dosage form results in a plasma half-life of from about 27 minutes and about 71 minutes or form about 20 to about 80 minutes.

131. The dissolvable drug dosage from according to claim 23, wherein said drug dosage form has a disintegration time of from about 15 minutes to about 8 hours and oral transmucosal administration of said drug dosage form results in a plasma half-life of from about 112 minutes and about 298 minutes or from about 100 to about 300 minutes.

134. The dissolvable drug dosage form according to claim 38, wherein said drug dosage form has a disintegration time of from about 30 seconds to about 30 minutes and oral transmucosal administration of said drug dosage form results in a plasma half-life of from about 32 minutes and about 50 minutes or from about 25 to about 100 minutes.

137. The dissolvable drug dosage form according to claim 6, wherein said drug dosage form has a disintegration time of from about 30 seconds to about 30 minutes and oral transmucosal administration of said drug dosage form results in a therapeutic time ratio of from about 0.08 to about 0.48 or from about 0.05 to about 0.5.

140. The dissolvable drug dosage form according to claim 6, wherein said drug dosage form has a disintegration time of from about 15 minutes to about 8 hours and oral transmucosal administration of said drug dosage form results in a therapeutic time ratio of from about 0.34 to about 1.82 or from about 0.3 to about 2.0.

143. The dissolvable drug dosage form according to claim 23, wherein said drug dosage form has a disintegration time of from about 30 seconds to about 30 minutes and oral transmucosal administration of said drug dosage form results in a therapeutic time ratio of from about 0.12 to about 0.44 or from about 0.05 to about 0.5.

146. The dissolvable drug dosage from according to claim 23, wherein said drug dosage form has a disintegration time of from about 15 minutes to about 8 hours and oral transmucosal administration of said drug dosage form results in a therapeutic time ratio of from about 0.42 to about 1.82 or from about 0.4 to about 2.0.

149. The dissolvable drug dosage form according to claim 38, wherein said drug dosage form has a disintegration time of from about 30 seconds to about 30 minutes and oral transmucosal administration of said drug dosage results in a therapeutic time ratio of from about 0.26 to about 0.4 or from about 0.1 to about 0.5.

152. A method of treating a subject exhibiting a symptomatic medical condition, comprising, administering the dissolvable drug dosage form according to claim 20, wherein said drug dosage form comprises a pharmaceutically active amount of a drug effective to reduce or eliminate said symptoms in the subject.

155. The method according to claim 104, wherein said symptomatic medical condition is pain.

158. A method of a treating pain in a subject comprising, administering a dissolvable drug dosage form according to claim 20, wherein said drug dosage form comprises a pharmaceutically active amount of a drug effective to reduce or eliminate symptoms of pain, wherein following administration of said drug dosage form symptoms of pain are reduced or eliminated in said subject.

160. The method according to claim 158, wherein said symptomatic medical condition is acute pain.

161. The method according to claim 158, wherein said symptomatic medical condition is breakthrough pain.

162. The method according to claim 158, wherein said symptomatic medical condition is post-operative pain.

166. The method according to claim 160, wherein said symptomatic medical condition is acute pain.

167. The method according to claim 160, wherein said symptomatic medical condition is breakthrough pain.

168. The method according to claim 160, wherein said symptomatic medical condition is post-operative pain.

7. A bioadhesive eroding drug dosage form for oral transmucosal administration comprising a dissolvable drug formulation wherein said formulation contains a predetermined amount of a pharmaceutically active agent in an amount selected from the group consisting of 100 μ

g, 15 μ

g, 25 μ

g, 50 μ

g, 100 μ

g, 500 μ

g, 1 mg, 2 mg, 3 mg, 4 mg, 5 mg, 6 mg, 7 mg, 8 mg, 9 mg and 10 mg and a bioadhesive material, said bioadhesive material providing for adherence to the oral mucosal membrane of a subject, wherein upon contact with an aqueous fluid, the surface of said dosage form hydrates and erodes, without formation of a hydrogel.

10. The bioadhesive drug dosage form according to claim 7, wherein said dosage form has a mucoadhesive strength of greater than 500 dynes/cm².

13. The bioadhesive drug dosage form according to claim 7, wherein said dosage form has an erosion time of from 30 seconds up to a time selected from the group consisting of 1 minute, 2 minutes, 3 minutes, 4 minutes, 5 minutes, 10 minutes, 15 minutes, 30 minutes, 1 hour, 2 hours, 4 hours and 8 hours or longer.

16. The bioadhesive drug dosage form according to claim 7, wherein the amount of the drug in said dissolvable drug formulation absorbed via the oral mucosa is selected from the group consisting of at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98% and at least 99% of the drug in said dosage form.

21. The bioadhesive drug dosage form according to claim 7, wherein said pharmaceutically active agent is an opioid selected from the group consisting of sufentanil, alfentanil, fentanyl, lofentanil, carfentanil, remifentanil, trefentanil, and mirfentanil.

24. The bioadhesive drug dosage form according to claim 21, comprising a pharmaceutically active amount of sufentanil.

27. The bioadhesive drug dosage form according to claim 24, comprising from about 0.25 μ

g to 200 micrograms (μ

g) of sufentanil.

30. The bioadhesive drug dosage form according to claim 24, comprising from about 2.5 μ

g to 100 μ

g of sufentanil.

33. The bioadhesive drug dosage form according to claim 24, comprising from about 0.02 μ

g to 5 micrograms per kilogram (μ

g/kg) of sufentanil.

36. The bioadhesive drug dosage form according to claim 24, comprising about 2 μ

g, 5 μ

g or 10 μ

g of sufentanil.

39. The bioadhesive drug dosage form according to claim 21, comprising from about 10 μ

g to 10 mg of alfentanil.

42. The bioadhesive drug dosage form according to claim 21, comprising from about 2 μ

g to 1500 μ

g of fentanyl.

45. The bioadhesive drug dosage form according to claim 21, comprising from about 50 μ

g to 1500 μ

g of fentanyl.

48. The bioadhesive drug dosage form according to claim 21, comprising from about 200 μ

g to 1500 μ

g of fentanyl.

51. The bioadhesive drug dosage form according to claim 21, comprising from about 0.25 μ

g to 99.9 mg of lofentanil.

54. The bioadhesive drug dosage form according to claim 21, comprising from about 0.25 μ

g to 99.9 mg of carfentanil.

57. The bioadhesive drug dosage form according to claim 21, comprising from about 0.25 μ

g to 99.9 mg of remifentanil.

60. The bioadhesive drug dosage form according to claim 21, comprising from about 0.25 μ

g to 99.9 mg of trefentanil.

63. The bioadhesive drug dosage form according to claim 21, comprising from about 0.25 μ

g to 99.9 mg of mirfentanil.

66. The bioadhesive drug dosage form according to claim 21, wherein a single or repeated oral transmucosal administration to a subject results in a bioavailability of greater than 70%.

69. The bioadhesive drug dosage form according to claim 21, wherein a single or repeated oral transmucosal administration to a subject results in a bioavailability of greater than 75%.

72. The bioadhesive drug dosage form according to claim 21, wherein a single or repeated oral transmucosal administration to a subject results in a bioavailability of greater than 85%.

75. The bioadhesive drug dosage form according to claim 21, wherein a single or repeated oral transmucosal administration to a subject results in a bioavailability of greater than 90%.

78. The bioadhesive drug dosage form according to claim 21, wherein a single or repeated oral transmucosal administration to a subject results in a bioavailability of greater than 94%.

81. The bioadhesive drug dosage form according to claim 21, wherein a single or repeated oral transmucosal administration to a subject results in a bioavailability with a coefficient of variation of less than 30%.

84. The bioadhesive drug dosage form according to claim 21, wherein a single or repeated oral transmucosal administration to a subject results in a bioavailability with a coefficient of variation of less than 40%.

87. The dissolvable drug dosage form according to claim 21, wherein a single oral transmucosal administration of said drug dosage form to a subject results in a C_max with a coefficient of variation of less than 30%.

90. The dissolvable drug dosage form according to claim 21, wherein a single oral transmucosal administration of said drug dosage form to a subject results in a C_max with a coefficient of variation of less than 40%.

93. The dissolvable drug dosage form according to claim 21, wherein a single oral transmucosal administration of said drug dosage form to a subject results in a T_max of from about 5 minutes to about 2 hours.

96. The dissolvable drug dosage form according to claim 21, wherein a single oral transmucosal administration of said drug dosage form results in a plasma level that reaches 50% of C_max in a time selected from about 3 minutes to 2 hours, from about 3 minutes to 30 minutes, from about 3 minutes to 20 minutes and from about 3 minutes to 10 minutes.

99. The dissolvable drug dosage form according to claim 21, wherein a single oral transmucosal administration of said drug dosage form results in a plasma half-life of from about 5 minutes and about 6 hours.

102. The dissolvable drug dosage form according to claim 21, wherein a single oral transmucosal administration of said drug dosage form results in a therapeutic time ratio of greater than 0.07.

105. The dissolvable drug dosage form according to claim 21, wherein a single oral transmucosal administration of said drug dosage form results in a therapeutic time ratio of from about 0.5 to about 2.0.

108. The dissolvable drug dosage form according to claim 7, wherein said drug dosage form has a disintegration time of from about 30 seconds to about 30 minutes and oral transmucosal administration of said drug dosage form results in a time of onset (T_onset) of from about 3 minutes to about 23 or 30 minutes.

111. The dissolvable drug dosage form according to claim 7, wherein said drug dosage form has a disintegration time of from about 15 minutes to about 8 hours and oral transmucosal administration of said drug dosage form results in a time of onset (T_onset) of from about 14 minutes to about 82 minutes or from about 10 minutes to about 100 minutes.

114. The dissolvable drug dosage form according to claim 24, wherein said drug dosage form has a disintegration time of from about 30 seconds to about 30 minutes and oral transmucosal administration of said drug dosage form results in a time of onset (T_onset) of from about 3 minutes to about 13.5 or 15 minutes.

117. The dissolvable drug dosage form according to claim 24, wherein said drug dosage form has a disintegration time of from about 15 minutes to about 8 hours and oral transmucosal administration of said drug dosage form results in a time of onset (T_onset) of from about 14 minutes to about 82 minutes or from about 10 minutes to about 100 minutes.

120. The dissolvable drug dosage form according to claim 39, wherein said drug dosage form has a disintegration time of from about 30 seconds to about 30 minutes and oral transmucosal administration of said drug dosage form results in a time of onset (T_onset) of from about 10 minutes to about 30 minutes.

123. The dissolvable drug dosage form according to claim 7, wherein said drug dosage form has a disintegration time of from about 30 seconds to about 30 minutes and oral transmucosal administration of said drug dosage form results in a plasma half-life of from about 20 minutes and about 140 minutes.

126. The dissolvable drug dosage form according to claim 7, wherein said drug dosage form has a disintegration time of from about 15 minutes to about 8 hours and oral transmucosal administration of said drug dosage form results in a plasma half-life of from about 100 minutes and about 300 minutes.

129. The dissolvable drug dosage form according to claim 24, wherein said drug dosage form has a disintegration-time of from about 30 seconds to about 30 minutes and oral transmucosal administration of said drug dosage form results in a plasma half-life of from about 27 minutes and about 71 minutes or form about 20 to about 80 minutes.

132. The dissolvable drug dosage form according to claim 24, wherein said drug dosage form has a disintegration time of from about 15 minutes to about 8 hours and oral transmucosal administration of said drug dosage form results in a plasma half-life of from about 112 minutes and about 298 minutes or from about 100 to about 300 minutes.

135. The dissolvable drug dosage form according to claim 39, wherein said drug dosage form has a disintegration time of from about 30 seconds to about 30 minutes and oral transmucosal administration of said drug dosage form results in a plasma half-life of from about 32 minutes and about 50 minutes or from about 25 to about 100 minutes.

138. The dissolvable drug dosage form according to claim 7, wherein said drug dosage form has a disintegration time of from about 30 seconds to about 30 minutes and oral transmucosal administration of said drug dosage form results in a therapeutic time ratio of from about 0.08 to about 0.48 or from about 0.05 to about 0.5.

141. The dissolvable drug dosage form according to claim 7, wherein said drug dosage form has a disintegration time of from about 15 minutes to about 8 hours and oral transmucosal administration of said drug dosage form results in a therapeutic time ratio of from about 0.34 to about 1.82 or from about 0.3 to about 2.0.

144. The dissolvable drug dosage form according to claim 24, wherein said drug dosage form has a disintegration time of from about 30 seconds to about 30 minutes and oral transmucosal administration of said drug dosage form results in a therapeutic time ratio of from about 0.12 to about 0.44 or from about 0.05 to about 0.5.

147. The dissolvable drug dosage form according to claim 24, wherein said drug dosage form has a disintegration time of from about 15 minutes to about 8 hours and oral transmucosal administration of said drug dosage form results in a therapeutic time ratio of from about 0.42 to about 1.82 or from about 0.4 to about 2.0.

150. The dissolvable drug dosage form according to claim 39, wherein said drug dosage form has a disintegration time of from about 30 seconds to about 30 minutes and oral transmucosal administration of said drug dosage form results in a therapeutic time ratio of from about 0.26 to about 0.4 or from about 0.1 to about 0.5.

153. A method of treating a subject exhibiting a symptomatic medical condition, comprising, administering the dissolvable drug dosage form according to claim 21, wherein said drug dosage form comprises a pharmaceutically active amount of a drug effective to reduce or eliminate said symptoms in the subject.

156. The method according to claim 105, wherein said symptomatic medical condition is pain.

159. A method of a treating pain in a subject comprising, administering a dissolvable drug dosage form according to claim 21, wherein said drug dosage form comprises a pharmaceutically active amount of a drug effective to reduce or eliminate symptoms of pain, wherein following administration of said drug dosage form symptoms of pain are reduced or eliminated in said subject.

163. The method according to claim 159, wherein said symptomatic medical condition is acute pain.

164. The method according to claim 159, wherein said symptomatic medical condition is breakthrough pain.

165. The method according to claim 159, wherein said symptomatic medical condition is post-operative pain.