Claims for Patent: 5,785,989

Summary for Patent: 5,785,989

Title:	Compositions and methods of manufacturing of oral dissolvable medicaments
Abstract:	Compositions and methods of manufacture for producing a medicament composition capable of absorption through the mucosal tissues of the mouth, pharynx, and esophagus. The present invention relates to such compositions and methods which are useful in administering lipophilic and nonlipophilic drugs in a dose-to-effect manner such that sufficient drug is administered to produce precisely a desired effect. The invention also relates to a manufacturing technique that enables a therapeutic agent or drug to be incorporated into a flavored dissolvable matrix. An appliance or holder is preferably attached to the dissolvable matrix. Employing the present invention the drug may be introduced into the patient's bloodstream almost as fast as through injection, and much faster than using the oral administration route, while avoiding the negative aspects of both of these methods. The present invention achieves these advantages by incorporating the drug into a carbohydrate, fat, protein, wax, or other dissolvable matrix composition. The dissolvable matrix may include permeation enhancers to increase the drug absorption by the mucosal tissues of the mouth. The matrix composition may also include pH buffering agents to modify the salival pH thereby increasing the absorption of the drug through the mucosal tissues.
Inventor(s):	Stanley; Theodore H. (Salt Lake City, UT), Hague; Brian (West Valley City, UT)
Assignee:	University Utah Research Foundation (Salt Lake City, UT)
Application Number:	08/822,560
Patent Claims:	1. A solid drug-containing dosage-from for use in the transmucosal oral and sublingual delivery of the drug to a patient, said solid dosage-form consisting essentially of: a soluble matrix selected from the group consisting of a carbohydrate, wax, fat, protein, or mixture thereof; buffers dispersed throughout the soluble matrix; a pharmacologically effective dose of a drug being capable of absorption through mucosal tissues of the mouth, pharynx, and esophagus and being dispersed throughout the matrix and formed into a solid integral mass which is capable of being sucked on while held within the mouth to dissolve the integral mass in the mouth of the patient to release the drug for absorption through mucosal tissues of the mouth, pharynx, and esophagus during the period of holding within the mouth resulting in dissolution of the integral mass in the mouth of the patient; and attached holder means secured to the integral mass so as to form a drug-containing dosage-form, the holder means being configured to permit convenient insertion and removal of the drug-containing integral mass into and out of the mouth of the patient and to permit administration of the dosage form in a dose-to-effect manner. 2. A drug-containing dosage-form for use in transmucosal delivery of the drug to a patient as defined in claim 1, wherein the soluble matrix further includes a water-insoluble component dispersed throughout the matrix in order to slow the dissolution of the matrix in the mouth of the patient. 3. A drug-containing dosage-form for use in transmucosal delivery of the drug to a patient as defined in claim 1, wherein the drug is lipophilic. 4. A drug-containing dosage-form for use in transmucosal delivery of the drug to a patient as defined in claim 1, wherein the drug is nonlipophilic. 5. A drug-containing dosage-form as recited in claim 1, wherein the drug is a central nervous system-acting drug. 6. A drug-containing dosage-form as recited in claim 1, wherein the drug is dispersed uniformally throughout the matrix. 7. A drug-containing dosage-form as recited in claim 1, wherein the drug is methohexital. 8. A drug-containing dosage-form as recited in claim 1, wherein the drug is pentobarbital. 9. A drug-containing dosage-form as recited in claim 1, wherein the drug thiamylal. 10. A drug-containing dosage-form as recited in claim 1, wherein the drug is thiopental. 11. A drug-containing dosage-form as recited in claim 1, wherein the drug is hexabarbital. 12. A drug-containing dosage-form as recited in claim 1, wherein the drug is fentanyl. 13. A drug-containing dosage-form as recited in claim 1, wherein the drug is alfentanil. 14. A drug-containing dosage-form as recited in claim 1, wherein the drug is sufentanil. 15. A drug-containing dosage-form as recited in claim 1, wherein the drug is lofentanil. 16. A drug-containing dosage-form as recited in claim 1, wherein the drug is carfentanil. 17. A drug-containing dosage-form as recited in claim 1, wherein the drug is naloxone. 18. A drug-containing dosage-form as recited in claim 1, wherein the drug is nalbuphine. 19. A drug-containing dosage-form as recited in claim 1, wherein the drug is diazepam. 20. A drug-containing dosage-form as recited in claim 1, wherein the drug is lorazepam. 21. A drug-containing dosage-form as recited in claim 1, wherein the drug is lormetazepam. 22. A drug-containing dosage-form as recited in claim 1, wherein the drug is midazolam. 23. A drug-containing dosage-form as recited in claim 1, wherein the drug is oxazepam. 24. A drug-containing dosage-form as recited in claim 1, wherein the drug is triazolam. 25. A drug-containing dosage-form as recited in claim 1, wherein the drug is droperidol. 26. A drug-containing dosage-form as recited in claim 1, wherein the drug is haloperidol. 27. A drug-containing dosage-form as recited in claim 1, wherein the drug is propanidid. 28. A drug-containing dosage-form as recited in claim 1, wherein the drug is etomidate. 29. A drug-containing dosage-form as recited in claim 1, wherein the drug is propofol. 30. A drug-containing dosage-form as recited in claim 1, wherein the drug is ketamine. 31. A drug-containing dosage-form as recited in claim 1, wherein the drug is levodopa. 32. A drug-containing dosage-form as recited in claim 1, wherein the drug is bretylium. 33. A drug-containing dosage-form as recited in claim 1, wherein the drug is captopril. 34. A drug-containing dosage-form as recited in claim 1, wherein the drug is clonidine. 35. A drug-containing dosage-form as recited in claim 1, wherein the drug is dopamine. 36. A drug-containing dosage-form as recited in claim 1, wherein the drug is enalapril. 37. A drug-containing dosage-form as recited in claim 1, wherein the drug is esmolol. 38. A drug-containing dosage-form as recited in claim 1, wherein the drug is furosemide. 39. A drug-containing dosage-form as recited in claim 1, wherein the drug is isosorbide. 40. A drug-containing dosage-form as recited in claim 1, wherein the drug is labetalol. 41. A drug-containing dosage-form as recited in claim 1, wherein the drug is lidocaine. 42. A drug-containing dosage-form as recited in claim 1, wherein the drug is metolazone. 43. A drug-containing dosage-form as recited in claim 1, wherein the drug is metoprolol. 44. A drug-containing dosage-form as recited in claim 1, wherein the drug is nadolol. 45. A drug-containing dosage-form as recited in claim 1, wherein the drug is nifedipine. 46. A drug-containing dosage-form as recited in claim 1, wherein the drug is nitroglycerin. 47. A drug-containing dosage-form as recited in claim 1, wherein the drug is nitroprusside. 48. A drug-containing dosage-form as recited in claim 1, wherein the drug is propranolol. 49. A drug-containing dosage-form as recited in claim 1, wherein the drug is benzquinamide. 50. A drug-containing dosage-form as recited in claim 1, wherein the drug is meclizine. 51. A drug-containing dosage-form as recited in claim 1, wherein the drug is metoclopramide. 52. A drug-containing dosage-form as recited in claim 1, wherein the drug is prochlorperazine. 53. A drug-containing dosage-form as recited in claim 1, wherein the drug is trimethobenzamide. 54. A drug-containing dosage-form as recited in claim 1, wherein the drug is clotrimazole. 55. A drug-containing dosage-form as recited in claim 1, wherein the drug is nystatin. 56. A drug-containing dosage-form as recited in claim 1, wherein the drug is carbidopa. 57. A drug-containing dosage-form as recited in claim 1, wherein the drug is sucralfate. 58. A drug-containing dosage-form as recited in claim 1, wherein the drug is albuterol. 59. A drug-containing dosage-form as recited in claim 1, wherein the drug is aminophylline. 60. A drug-containing dosage-form as recited in claim 1, wherein the drug is beclomethasone. 61. A drug-containing dosage-form as recited in claim 1, wherein the drug is dyphylline. 62. A drug-containing dosage-form as recited in claim 1, wherein the drug is epinephrine. 63. A drug-containing dosage-form as recited in claim 1, wherein the drug is flunisolide. 64. A drug-containing dosage-form as recited in claim 1, wherein the drug is isoetharine. 65. A drug-containing dosage-form as recited in claim 1, wherein the drug is isoproterenol HCL. 66. A drug-containing dosage-form as recited in claim 1, wherein the drug is metaproterenol. 67. A drug-containing dosage-form as recited in claim 1, wherein the drug is oxtriphylline. 68. A drug-containing dosage-form as recited in claim 1, wherein the drug is terbutaline. 69. A drug-containing dosage-form as recited in claim 1, wherein the drug is theophylline. 70. A drug-containing dosage-form as recited in claim 1, wherein the drug is ergotamine. 71. A drug-containing dosage-form as recited in claim 1, wherein the drug is dihydroergotamine. 72. A drug-containing dosage-form as recited in claim 1, wherein the drug is methysergide. 73. A drug-containing dosage-form as recited in claim 1, wherein the drug is suloctidil. 74. A drug-containing dosage-form as recited in claim 1, wherein the drug is ergonovine. 75. A drug-containing dosage-form as recited in claim 1, wherein the drug is oxytocin. 76. A drug-containing dosage-form as recited in claim 1, wherein the drug is desmopressin acetate. 77. A drug-containing dosage-form as recited in claim 1, wherein the drug is lypressin. 78. A drug-containing dosage-form as recited in claim 1, wherein the drug is vasopressin. 79. A drug-containing dosage-form as recited in claim 1, wherein the drug is insulin. 80. A drug-containing dosage-form as recited in claim 1, wherein the drug is a B-endorphin. 81. A drug-containing dosage-form as recited in claim 1, wherein the drug is an enkephalin. 82. A drug-containing dosage-form as recited in claim 1, wherein the drug is a bradykinin. 83. A drug-containing dosage-form as recited in claim 1, wherein the drug is angiotensin I. 84. A drug-containing dosage-form as recited in claim 1, wherein the drug is a gonadotropic hormone. 85. A drug-containing dosage-form as recited in claim 1, wherein the drug is an adrenocorticotropic hormone. 86. A drug-containing dosage-form as recited in claim 1, wherein the drug is calcitonin. 87. A drug-containing dosage-form as recited in claim 1, wherein the drug is a parathyroid hormone. 88. A drug-containing dosage-form as recited in claim 1, wherein the drug is a growth hormone. 89. A drug-containing dosage-form as recited in claim 1, wherein the drug is heparin. 90. A drug-containing dosage-form as recited in claim 1, wherein the drug is a barbiturate. 91. A drug-containing dosage-form as recited in claim 1, wherein the drug is an opioid agonist. 92. A drug-containing dosage-form as recited in claim 1, wherein the drug is an opioid antagonist. 93. A drug-containing dosage-form as recited in claim 1, wherein the drug is a benzodiazepine. 94. A drug-containing dosage-form as recited in claim 1, wherein the drug is a butyrophenone. 95. A drug-containing dosage-form as recited in claim 1, wherein the drug is a GABA stimulator. 96. A drug-containing dosage-form as recited in claim 1, wherein the drug is a substituted phenol. 97. A drug-containing dosage-form as recited in claim 1, wherein the drug is a phencyclidine. 98. A drug-containing dosage-form as recited in claim 1, wherein the drug is an antiarrhythmic. 99. A drug-containing dosage-form as recited in claim 1, wherein the drug is a beta blocker. 100. A drug-containing dosage-form as recited in claim 1, wherein the drug is an ACE inhibitor. 101. A drug-containing dosage-form as recited in claim 1, wherein the drug is a calcium channel blocker. 102. A drug-containing dosage-form as recited in claim 1, wherein the drug is an antihypertensive. 103. A drug-containing dosage-form as recited in claim 1, wherein the drug is an antihypertensive/anti-anginal. 104. A drug-containing dosage-form as recited in claim 1, wherein the drug is a diuretic. 105. A drug-containing dosage-form as recited in claim 1, wherein the drug is anti-anginal. 106. A drug-containing dosage-form as recited in claim 1, wherein the drug is antihypertensive/anti-anginal/vasodilator-acting. 107. A drug-containing dosage-form as recited in claim 1, wherein the drug is a hypotensive-acting. 108. A drug-containing dosage-form as recited in claim 1, wherein the drug is an antiemetic. 109. A drug-containing dosage-form as recited in claim 1, wherein the drug is an antifungal. 110. A drug-containing dosage-form as recited in claim 1, wherein the drug is an antiparkinson. 111. A drug-containing dosage-form as recited in claim 1, wherein the drug is a bronchodilator. 112. A drug-containing dosage-form as recited in claim 1, wherein the drug is an antimigraine. 113. A drug-containing dosage-form as recited in claim 1, wherein the drug is an oxytocic. 114. A drug-containing dosage-form as recited in claim 1, wherein the drug is an antidiuretic. 115. A drug-containing dosage-form as recited in claim 1, wherein the drug is an antihyperglycemic. 116. A drug-containing dosage-form as recited in claim 1, wherein the drug is a macromolecular. 117. A drug-containing dosage-form as recited in claim 1, wherein the drug is an amino acid. 118. A drug-containing dosage-form as recited in claim 1, wherein the drug is a polysaccharide. 119. A drug-containing dosage-form as recited in claim 1, wherein the drug is a polypeptide. 120. A drug-containing dosage-form as recited in claim 1, wherein the drug is an antigen. 121. A drug-containing dosage-form as recited in claim 1, wherein the drug is a nucleoside. 122. A drug-containing dosage-form as recited in claim 1, wherein the drug is an antibody. 123. A drug-containing dosage-form as recited in claim 1, wherein the drug is a vitamin. 124. A drug-containing dosage-form as recited in claim 1, wherein the drug is an enzyme. 125. A drug-containing dosage-form as recited in claim 1, wherein the drug is central nervous system-acting. 126. A drug-containing dosage-form as recited in claim 1, wherein the drug is cardiovascular-acting. 127. A drug-containing dosage-form as recited in claim 1, wherein the drug is renal vascular-acting. 128. A drug-containing dosage-form as recited in claim 1, wherein the drug is a sedative. 129. A drug-containing dosage-form as recited in claim 1, wherein the drug is anxiolytic. 130. A drug-containing dosage-form as recited in claim 1, wherein the drug is analgesic. 131. A drug-containing dosage-form as recited in claim 1, wherein the drug is an amnestic. 132. A drug-containing dosage-form as recited in claim 1, wherein the drug is an anesthetic. 133. A drug-containing dosage-form as recited in claim 1, wherein the drug is a local anesthetic agent. 134. A drug-containing dosage-form as recited in claim 1, wherein the drug is an antiplaque agent. 135. A drug-containing dosage-form as recited in claim 1, wherein the drug is a local antipruritic agent. 136. A drug-containing dosage-form as recited in claim 1, wherein the drug is a local antisecretory agent. 137. A drug-containing dosage-form as recited in claim 1, wherein the drug is a local antifungal agent. 138. A drug-containing dosage-form as recited in claim 1, wherein the drug is an antibiotic. 139. A drug-containing dosage-form as recited in claim 1, wherein the drug is nicotine. 140. A drug-containing dosage-form as recited in claim 1, wherein the drug is atropine. 141. A drug-containing dosage-form as recited in claim 1, wherein the drug is scopolamine. 142. A drug-containing dosage-form as recited in claim 1, wherein the drug is ondansetron. 143. A drug-containing dosage-form as recited in claim 1, wherein the drug is sumatriptan. 144. A drug-containing dosage-form as recited in claim 1, wherein the drug is ketorolac tromethamine. 145. A drug-containing dosage-form as recited in claim 1, wherein the drug is meclofenamate. 146. A drug-containing dosage-form as recited in claim 1, wherein the drug is piroxicam. 147. A drug-containing dosage-form as recited in claim 1, wherein the drug is ketoprofen. 148. A drug-containing dosage-form as recited in claim 1, wherein the drug is indomethacin. 149. A drug-containing dosage-form as recited in claim 1, wherein the drug is ibuprofen. 150. A drug-containing dosage-form as recited in claim 1, wherein the drug is diclofenac. 151. A drug-containing dosage-form as recited in claim 1, wherein the drug is flurbiprofen. 152. A drug-containing dosage-form as recited in claim 1, wherein the drug comprises a permeation enhancer. 153. A drug-containing dosage-form as recited in claim 1, wherein the drug is sodium cholate. 154. A drug-containing dosage-form as recited in claim 1, wherein the drug is sodium dodecyl sulfate. 155. A drug-containing dosage-form as recited in claim 1, wherein the drug is sodium deoxycholate. 156. A drug-containing dosage-form as recited in claim 1, wherein the drug is taurodeoxycholate. 157. A drug-containing dosage-form as recited in claim 1, wherein the drug is sodium glycocholate. 158. A drug-containing dosage-form as recited in claim 1, wherein the drug is sodium taurocholate. 159. A drug-containing dosage-form as recited in claim 1, wherein the drug is dimethyl sulfoxide. 160. A drug-containing dosage-form as recited in claim 1, wherein the drug is sodium glycodeoxycholate. 161. A drug-containing dosage-form as recited in claim 1, wherein the drug is sodium lithocholoate chenocholate. 162. A drug-containing dosage-form as recited in claim 1, wherein the drug is chenodeoxycholate. 163. A drug-containing dosage-form as recited in claim 1, wherein the drug is ursocholate. 164. A drug-containing dosage-form as recited in claim 1, wherein the drug is ursodeoxycholate. 165. A drug-containing dosage-form as recited in claim 1, wherein the drug is hydrodeoxycholate. 166. A drug-containing dosage-form as recited in claim 1, wherein the drug is dehydrocholate. 167. A drug-containing dosage-form as recited in claim 1, wherein the drug is glycochenocholate. 168. A drug-containing dosage-form as recited in claim 1, wherein the drug is taurochenocholate. 169. A drug-containing dosage-form as recited in claim 1, wherein the drug is taurochenodeoxycholate. 170. A drug-containing dosage-form as recited in claim 1, wherein the drug is sodium lauryl sulfate. 171. A drug-containing dosage-form as recited in claim 1, wherein the drug is salts. 172. A drug-containing dosage-form as recited in claim 1, wherein the drug is alcohol. 173. A drug-containing dosage-form as recited in claim 1, wherein the drug is ethanol. 174. A drug-containing dosage-form as recited in claim 1, wherein the drug is deanol. 175. A drug-containing dosage-form as recited in claim 1, wherein the drug is benzyl alcohol. 176. A drug-containing dosage-form as recited in claim 1, wherein the drug is caffeine. 177. A drug-containing dosage-form as recited in claim 1, wherein the drug is vitamin B.sub.6. 178. A drug-containing dosage-form as recited in claim 1, wherein the drug is benzoic acid. 179. A drug-containing dosage-form as recited in claim 1, wherein the drug is laurocapram. 180. A drug-containing dosage-form as recited in claim 1, wherein the drug is 2-hydroxypropyl-.beta.-cyclodextrin. 181. A drug-containing dosage-form as recited in claim 1, wherein the drug is propylene glycol. 182. A drug-containing dosage-form as recited in claim 1, wherein the drug is a buffer. 183. A drug-containing dosage-form as recited in claim 1, wherein the drug is N-methyl pyrrolidone. 184. A drug-containing dosage-form as recited in claim 1, wherein the drug is polyoxyethylene-9-lauryl ether. 185. A drug-containing dosage-form as recited in claim 1, wherein the drug is polyethylene oxide. 186. A drug-containing dosage-form as recited in claim 1, wherein the drug is poleythylene glycol and its derivatives. 187. A drug-containing dosage-form as recited in claim 1, wherein the drug is polyvinyl alcohol. 188. A drug-containing dosage-form as recited in claim 1, wherein the drug is polyvinyl pyrrolidone. 189. A drug-containing dosage-form as recited in claim 1, wherein the drug is a 5-HT agonist. 190. A drug-containing dosage-form as recited in claim 1, wherein the drug is a nonsteroidal anti-inflammatory drug. 191. A drug-containing dosage-form as recited in claim 1, wherein the drug is an antithrombotic. 192. A drug-containing dosage-form as recited in claim 1, wherein the drug is a ganglionic stimulant. 193. A drug-containing dosage-form as recited in claim 1, wherein the drug is an antimuscarinic. 194. A drug-containing dosage-form as recited in claim 1, wherein the drug is a cessation of smoking agent. 195. A drug-containing dosage-form as recited in claim 1, wherein the drug is diprivan. 196. A drug-containing dosage-form as recited in claim 1, wherein the drug is propanolol. 197. A drug-containing dosage-form as recited in claim 1, wherein the drug is bile salt and its derivatives. 198. A drug-containing dosage-form as recited in claim 1, wherein the drug is a fatty acid.