WO2004062642B1 - Pharmaceutical safety dosage forms - Google Patents

Pharmaceutical safety dosage forms

Info

Publication number
WO2004062642B1
WO2004062642B1 PCT/US2003/040990 US0340990W WO2004062642B1 WO 2004062642 B1 WO2004062642 B1 WO 2004062642B1 US 0340990 W US0340990 W US 0340990W WO 2004062642 B1 WO2004062642 B1 WO 2004062642B1
Authority
WO
WIPO (PCT)
Prior art keywords
pharmaceutical
safety dosage
dosage form
pharmaceutical safety
derivatives
Prior art date
Application number
PCT/US2003/040990
Other languages
French (fr)
Other versions
WO2004062642A1 (en
Inventor
Richard H Roberts
Original Assignee
Mutual Pharmaceutical Co
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Mutual Pharmaceutical Co filed Critical Mutual Pharmaceutical Co
Priority to CA2505661A priority Critical patent/CA2505661C/en
Priority to JP2004566589A priority patent/JP2006514067A/en
Priority to EP03800100A priority patent/EP1581188A4/en
Priority to AU2003299826A priority patent/AU2003299826A1/en
Publication of WO2004062642A1 publication Critical patent/WO2004062642A1/en
Publication of WO2004062642B1 publication Critical patent/WO2004062642B1/en

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
    • A61K9/0004—Osmotic delivery systems; Sustained release driven by osmosis, thermal energy or gas
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
    • A61K9/2077—Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
    • A61K9/2081—Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets with microcapsules or coated microparticles according to A61K9/50
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
    • A61K9/2086—Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat
    • A61K9/209—Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat containing drug in at least two layers or in the core and in at least one outer layer
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5073—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals having two or more different coatings optionally including drug-containing subcoatings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5084—Mixtures of one or more drugs in different galenical forms, at least one of which being granules, microcapsules or (coated) microparticles according to A61K9/16 or A61K9/50, e.g. for obtaining a specific release pattern or for combining different drugs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/12—Antihypertensives

Abstract

Pharmaceutical safety dosage forms are provided which include a pharmaceutical and an antagonist to the pharmaceutical. The safety dosage forms are such that the antagonist has no significant bioavailability when the pharmaceutical safety dosage form is administered as intended. However, the antagonist is released and becomes bioavailable if the dosage form is disrupted. Methods of administering pharmaceuticals by providing pharmaceutical safety dosage forms are also provided.

Claims

AMENDED CLAIMS[received by the International Bureau on 31 August 2004 (31.08.04) Sheets 17 - 43 are replaced by sheeets 17 - 56. ]What is Claimed is:
1. A pharmaceutical safety dosage form comprising a pharmaceutical and an antagonist for said pharmaceutical wherein said antagonist comprises an emetic agent and has significant bioavailability only when said pharmaceutical safety dosage form is disrupted.
2. The pharmaceutical safety dosage of claim 1 wherein said pharmaceutical is adapted for time-release, or said antagonist further comprises an insoluble coating, or both.
3. The pharmaceutical safety dosage form of claim 1 wherein said bioavailability occurs upon mechanical disruption.
4. The pharmaceutical safety dosage form of claim 1 wherein said bioavailability occurs upon extraction by a chemical.
5. The pharmaceutical safety dosage form of claim 1 adapted to be administered orally.
6. The pharmaceutical safety dosage form of claim 1 adapted to be administered rectally, parenterally, vaginally, transdermally, intranasally, or via aerosol.
7. (Canceled)
8. The pharmaceutical safety dosage form of claim 1 wherein said emetic agent is ipecac or derivatives thereof.
9. The pharmaceutical safety dosage form of claim 1 wherein said pharmaceutical comprises a narcotic.
44
10. The pharmaceutical safety dosage form of claim 9 wherein said narcotic is codeine, oxycodone, propoxyphene, pentazocine, derivatives thereof, or combinations thereof.
11. The pharmaceutical safety dosage form of claim 9 wherein said antagonist further comprises naloxone, nalmefene, derivatives thereof, or combinations thereof.
12. The pharmaceutical safety dosage form of claim 1 wherein said pharmaceutical comprises a sympathomimetic.
13. The pharmaceutical safety dosage form of claim 12 further comprising an antihistamine.
14. The pharmaceutical safety dosage form of claim 13 wherein said sympathomimetic is pseudoephedrine HCl or derivatives thereof, and said antihistamine is cetirizine HCl, fexofenadine HCl, derivatives thereof, or combinations thereof.
15. The pharmaceutical safety dosage form of claim 13 wherein said antagonist further comprises an adrenergic beta blocker.
16. The pharmaceutical safety dosage form of claim 12 wherein said sympathomimetic comprises methylphenidate.
17. The pharmaceutical safety dosage form of claim 16 wherein said antagonist further comprises an adrenergic beta blocker.
18. The pharmaceutical safety dosage form of claim 12 wherein said sympathomimetic comprises an amphetamine.
45
19. The pharmaceutical safety dosage form of claim 18 wherein said amphetamine is methamphetamine, amphetamine, dextroamphetamme, derivatives thereof, or combinations thereof.
20. The pharmaceutical safety dosage form of claim 18 wherein said antagonist further comprises an adrenergic beta blocker.
21. The pharmaceutical safety dosage form of claim 20 wherein said adrenergic beta blocker is propranolol, atenolol, metoprolol, derivatives thereof, or combinations thereof.
22. The pharmaceutical safety dosage form of claim 1 wherein said pharmaceutical comprises a blood pressure-lowering medication.
23. The pharmaceutical safety dosage form of claim 22 wherein said blood pressure-lowering medication is an adrenergic beta blocker, a calcium channel blocker, or an ACE inhibitor.
24. The pharmaceutical safety dosage form of claim 23 wherein said blood pressure-lowering medication is propranolol, metoprolol, nifedipine, diltiazem, nisoldipine, timolol maleate, derivatives thereof, or combinations thereof.
25. The phaπnaceutical safety dosage form of claim 22 wherein said antagonist further comprises a sympathomimetic.
26. The pharmaceutical safety dosage form of claim 25 wherein said sympathomimetic is dopamine, epinepherine, derivatives thereof, or combinations thereof.
46
27. The pharmaceutical safety dosage form of claim 1 wherein said pharmaceutical comprises a hypoglycemic agent.
28. The pharmaceutical safety dosage form of claim 27 wherein said hypoglycemic agent is insulin, metformin, glipizide, glyburide, derivatives thereof, or combinations thereof.
29. The pharmaceutical safety dosage form of claim 27 wherein said antagonist further comprises a hyperglycemic agent.
30. The pharmaceutical safety dosage form of claim 29 wherein said hyperglycemic agent is epinepherine, glucagon, derivatives thereof, or combinations thereof.
31. A pharmaceutical safety dosage form comprising a pharmaceutical contained within a first microdosage form, said first microdosage form being adapted for release of said phaπnaceutical within a patient, together with an antagonist for said pharmaceutical, said antagonist comprising an emetic agent and being contained within a second microdosage form, said second microdosage form being substantially insoluble in gastric fluid.
32. The pharmaceutical safety dosage foπn of claim 31 wherein said pharmaceutical is adapted for time-release, or said second microdosage form comprises a coating which is substantially insoluble in gastric fluid, or both.
33. The pharmaceutical safety dosage form of claim 31 wherein said first microdosage form comprises beads, tablets, mini tablets, or combinations thereof; or second microdosage forms comprises beads, tablets, mini tablets, or combinations thereof; or both.
34. The pharmaceutical safety dosage form of claim 31 adapted to be administered orally.
35. The pharmaceutical safety dosage foπn of claim 31 adapted to be administered rectally, parenterally, vaginally, transdermally, intranasally, or via aerosol.
36. (Canceled)
37. The pharmaceutical safety dosage form of claim 31 wherein said emetic agent is ipecac or derivatives thereof.
38. The pharmaceutical safety dosage form of claim 31 wherein said pharmaceutical comprises a narcotic.
39. The pharmaceutical safety dosage form of claim 38 wherein said narcotic is codeine, oxycodone, propoxyphene, pentazocine, derivatives thereof, or combinations thereof.
40. The pharmaceutical safety dosage form of claim 38 wherein said antagonist further comprises naloxone, nalmefene, derivatives thereof, or combinations thereof.
41. The pharmaceutical safety dosage form of claim 31 wherein said pharmaceutical comprises a sympathomimetic.
42. The pharmaceutical safety dosage form of claim 41 further comprising an antihistamine.
43. The pharmaceutical safety dosage form of claim 42 wherein said sympathomimetic is pseudoephedrine HCl or derivatives thereof, and said antihistamine is cetirizine HCl, fexofenadine HCl, derivatives thereof, or combinations thereof.
48
44. The pharmaceutical safety dosage form of claim 42 wherein said antagonist further comprises an adrenergic beta blocker.
45. The pharmaceutical safety dosage form of claim 41 wherein said sympathomimetic comprises methylphenidate.
46. The pharmaceutical safety dosage form of claim 45 wherein said antagonist further comprises an adrenergic beta blocker.
47. The pharmaceutical safety dosage form of claim 41 wherein said sympathomimetic comprises an amphetamine.
48. The pharmaceutical safety dosage form of claim 47 wherein said amphetamine is methamphetamine, amphetamine, dextroamphetamme, derivatives thereof, or combinations thereof.
49. The pharmaceutical safety dosage form of claim 47 wherein said antagonist further comprises an adrenergic beta blocker.
50. The pharmaceutical safety dosage form of claim 49 wherein said adrenergic beta blocker is propranolol, atenolol, metoprolol, derivatives thereof, or combinations thereof.
51. The pharmaceutical safety dosage form of claim 31 wherein said pharmaceutical comprises a blood pressure-lowering medication.
49
52. The phannaceutical safety dosage form of claim 51 wherein said blood pressure-lowering medication is an adrenergic beta blocker, a calcium channel blocker, or an ACE inhibitor.
53. The pharmaceutical safety dosage foπn of claim 52 wherein said blood pressure-lowering medication is propranolol, metoprolol, nifedipine, diltiazem, nisoldipine, timolol maleate, derivatives thereof, or combinations thereof.
54. The phaπnaceutical safety dosage foπn of claim 51 wherein said antagonist further comprises a sympathomimetic.
55. The pharmaceutical safety dosage form of claim 54 wherein said sympathomimetic is dopamine, epinepherine, derivatives thereof, or combinations thereof.
56. The phannaceutical safety dosage form of claim 31 wherein said pharmaceutical comprises a hypoglycemic agent.
57. The pharmaceutical safety dosage form of claim 56 wherein said hypoglycemic agent is insulin, metformin, glipizide, glyburide, derivatives thereof, or combinations thereof.
58. The pharmaceutical safety dosage fonn of claim 56 wherein said antagonist further comprises a hyperglycemic agent.
59. The pharmaceutical safety dosage form of claim 58 wherein said hyperglycemic agent is epinepherine, glucagon, derivatives thereof, or combinations thereof.
50
60. A pharmaceutical safety dosage form comprising a pharmaceutical contained within a first plurality of particulated forms, said first particulated forms being adapted for release of said phannaceutical within a patient, together with an antagonist for said pharmaceutical, said antagonist comprising an emetic agent and being contained within a second plurality of particulated forms, said second particulated forms being substantially insoluble in gastric fluid.
61. The pharmaceutical safety dosage form of claim 60 wherein said pharmaceutical is adapted for time-release, or said second plurality of particulated forms comprise a polymorph or a solvate which is substantially insoluble in gastric fluid, or both.
62. The pharmaceutical safety dosage form of claim 61 wherein said first plurality of particulated forms comprises a sustained-release powder.
63. The pharmaceutical safety dosage foπn of claim 60 adapted to be administered orally.
64. The pharmaceutical safety dosage form of claim 60 adapted to be administered rectally, parenterally, vaginally, transdermally, intranasally, or via aerosol.
65. (Canceled)
66. The pharmaceutical safety dosage form of claim 60 wherein said emetic agent is ipecac or derivatives thereof.
67. The pharmaceutical safety dosage fonn of claim 60 wherein said pharmaceutical comprises a narcotic.
51
68. The pharmaceutical safety dosage fonn of claim 67 wherein said narcotic is codeine, oxycodone, propoxyphene, pentazocine, derivatives thereof, or combinations thereof.
69. The phannaceutical safety dosage form of claim 67 wherein said antagonist further comprises naloxone, nalmefene, derivatives thereof, or combinations thereof.
70. The pharmaceutical safety dosage form of claim 60 wherein said pharmaceutical comprises a sympathomimetic.
71. The pharmaceutical safety dosage fonn of claim 70 further comprising an antihistamine.
72. The pharmaceutical safety dosage form of claim 71 wherein said sympathomimetic is pseudoephedrine HCl or derivatives thereof, and said antihistamine is cetirizine HCl, fexofenadine HCl, derivatives thereof, or combinations thereof.
73. The pharmaceutical safety dosage form of claim 71 wherein said antagonist further comprises an adrenergic beta blocker.
74. The pharmaceutical safety dosage form of claim 70 wherein said sympathomimetic comprises methylphenidate.
75. The pharmaceutical safety dosage fonn of claim 74 wherein said antagonist further comprises an adrenergic beta blocker.
76. The phannaceutical safety dosage foπn of claim 70 wherein said sympathomimetic comprises an amphetamine.
52 -77. The pharmaceutical safety dosage form of claim 76 wherein said amphetamine is methamphetamine, amphetamine, dextroamphetamme, derivatives thereof, or combinations thereof.
78. The pharmaceutical safety dosage form of claim 76 wherein said antagonist further comprises an adrenergic beta blocker.
79. The pharmaceutical safety dosage fonn of claim 78 wherein said adrenergic beta blocker is propranolol, atenolol, metoprolol, derivatives thereof, or combinations thereof.
80. The pharmaceutical safety dosage form of claim 60 wherein said pharmaceutical comprises a blood pressure-lowering medication.
81. The phannaceutical safety dosage form of claim 80 wherein said blood pressure-lowering medication is an adrenergic beta blocker, a calcium channel blocker, or an ACE inhibitor.
82. The pharmaceutical safety dosage form of claim 81 wherein said blood pressure-lowering medication is propranolol, metoprolol, nifedipine, diltiazem, nisoldipine, timolol maleate, derivatives thereof, or combinations thereof.
83. The pharmaceutical safety dosage form of claim 80 wherein said antagonist further comprises a sympathomimetic.
84. The pharmaceutical safety dosage form of claim 83 wherein said sympathomimetic is dopamine, epinepherine, derivatives thereof, or combinations thereof.
53
85. The pharmaceutical safety dosage form of claim 60 wherein said pharmaceutical comprises a hypoglycemic agent.
86. The pharmaceutical safety dosage form of claim 85 wherein said hypoglycemic agent is insulin, metformin, glipizide, glyburide, derivatives thereof, or combinations thereof.
87. The phannaceutical safety dosage fonn of claim 85 wherein said antagonist further comprises a hyperglycemic agent.
88. The pharmaceutical safety dosage form of claim 87 wherein said hyperglycemic agent is epinepherine, glucagon, derivatives thereof, or combinations thereof.
89. A pharmaceutical safety dosage form comprising a pharmaceutical contained within a microdosage fonn, said microdosage form being adapted for release of said pharmaceutical within a patient, together with an antagonist for said pharmaceutical, said antagonist comprising an emetic agent and being contained within a plurality of particulated dosage forms, said particulated dosage foπns being substantially insoluble in gastric fluid.
90. The pharmaceutical safety dosage foπn of claim 89 wherein said pharmaceutical is adapted for time-release, or said plurality of particulated forms comprise a polymorph which is substantially insoluble in gastric fluid, or both.
91. The pharmaceutical safety dosage form of claim 89 wherein said microdosage form comprises beads, tablets, mini tablets, or combinations thereof.
92. The phannaceutical safety dosage fonn of claim 89 adapted to be administered orally.
54
93. The phannaceutical safety dosage foπn of claim 89 adapted to be administered rectally, parenterally, vaginally, transdermally, intranasally, or via aerosol.
94. (Canceled)
95. The pharmaceutical safety dosage form of claim 89 wherein said emetic agent is ipecac or derivatives thereof.
96. The pharmaceutical safety dosage form of claim 89 wherein said pharmaceutical comprises a narcotic.
97. The pharmaceutical safety dosage fonn of claim 96 wherein said narcotic is codeine, oxycodone, propoxyphene, pentazocine, derivatives thereof, or combinations thereof.
98. The pharmaceutical safety dosage foπn of claim 96 wherein said antagonist further comprises naloxone, nalmefene, derivatives thereof, or combinations thereof.
99. The pharmaceutical safety dosage form of claim 89 wherein said phannaceutical comprises a sympathomimetic.
100. The pharmaceutical safety dosage foπn of claim 99 further comprising an antihistamine.
101. The pharmaceutical safety dosage form of claim 100 wherein said sympathomimetic is pseudoephedrine HCl or derivatives thereof, and said antihistamine is cetirizine HCl, fexofenadine HCl, derivatives thereof, or combinations thereof.
55
102. The pharmaceutical safety dosage form of claim 100 wherein said antagonist further comprises an adrenergic beta blocker.
103. The pharmaceutical safety dosage form of claim 99 wherein said sympathomimetic comprises methylphenidate.
104. The pharmaceutical safety dosage foπn of claim 103 wherein said antagonist further comprises an adrenergic beta blocker.
105. The pharmaceutical safety dosage fonn of claim 99 wherein said sympathomimetic comprises an amphetamine.
106. The pharmaceutical safety dosage form of claim 105 wherein said amphetamine is methamphetamine, amphetamine, dextroamphetamme, derivatives thereof, or combinations thereof.
107. The pharmaceutical safety dosage form of claim 105 wherein said antagonist further comprises an adrenergic beta blocker.
108. The pharmaceutical safety dosage form of claim 107 wherein said adrenergic beta blocker is propranolol, atenolol, metoprolol, derivatives thereof, or combinations thereof.
109. The pharmaceutical safety dosage fonn of claim 89 wherein said pharmaceutical comprises a blood pressure-lowering medication.
56
110. The phannaceutical safety dosage foπn of claim 109 wherein said blood pressure- lowering medication is an adrenergic beta blocker, a calcium channel blocker, or an ACE inhibitor.
111. The pharmaceutical safety dosage form of claim 110 wherein said blood pressure- lowering medication is propranolol, metoprolol, nifedipine, diltiazem, nisoldipine, timolol maleate, derivatives thereof, or combinations thereof.
112. The pharmaceutical safety dosage form of claim 109 wherein said antagonist further comprises a sympathomimetic.
113. The pharmaceutical safety dosage fonn of claim 112 wherein said sympathomimetic is dopamine, epinepherine, derivatives thereof, or combinations thereof.
114. The pharmaceutical safety dosage form of claim 89 wherein said pharmaceutical comprises a hypoglycemic agent.
115. The phannaceutical safety dosage fonn of claim 114 wherein said hypoglycemic agent is insulin, metformin, glipizide, glyburide, derivatives thereof, or combinations thereof.
116. The pharmaceutical safety dosage fonn of claim 114 wherein said antagonist further comprises a hyperglycemic agent.
117. The pharmaceutical safety dosage form of claim 116 wherein said hyperglycemic agent is epinepherine, glucagon, derivatives thereof, or combinations thereof.
57
118. A pharmaceutical safety dosage form comprising a pharmaceutical contained within a plurality of particulated forms, said particulated forms being adapted for release of said pharmaceutical within a patient, together with an antagonist for said pharmaceutical, said antagonist comprising an emetic agent and being contained within a microdosage form, said microdosage form being substantially insoluble in gastric fluid.
119. The pharmaceutical safety dosage form of claim 118 wherein said plurality of particulated forms comprise a polymorph which is substantially insoluble in gastric fluid, or said microdosage form comprises a coating which is substantially insoluble in gastric fluid, or both.
120. The pharmaceutical safety dosage foπn of claim 118 wherein said microdosage form comprises beads, tablets, mini tablets, or combinations thereof.
121. The pharmaceutical safety dosage form of claim 118 adapted to be administered orally.
122. The pharmaceutical safety dosage form of claim 118 adapted to be administered rectally, parenterally, vaginally, transdermally, intranasally, or via aerosol.
123. (Canceled)
124. The pharmaceutical safety dosage form of claim 118 wherein said emetic agent is ipecac or derivatives thereof.
125. The pharmaceutical safety dosage foπn of claim 118 wherein said pharmaceutical comprises a narcotic.
58
126. The pharmaceutical safety dosage form of claim 125 wherein said narcotic is codeine, oxycodone, propoxyphene, pentazocine, derivatives thereof, or combinations thereof.
127. The pharmaceutical safety dosage form of claim 125 wherein said antagonist further comprises naloxone, nalmefene, derivatives thereof, or combinations thereof.
128. The phannaceutical safety dosage foπn of claim 118 wherein said pharmaceutical comprises a sympathomimetic.
129. The pharmaceutical safety dosage fonn of claim 128 further comprising an antilristamine.
130. The pharmaceutical safety dosage fonn of claim 129 wherein said sympathomimetic is pseudoephedrine HCl or derivatives thereof, and said antihistamine is cetirizine HCl, fexofenadine HCl, derivatives thereof, or combinations thereof.
131. The pharmaceutical safety dosage form of claim 129 wherein said antagonist further comprises an adrenergic beta blocker.
132. The pharmaceutical safety dosage form of claim 128 wherein said sympathomimetic comprises methylphenidate.
133. The pharmaceutical safety dosage form of claim 132 wherein said antagonist further comprises an adrenergic beta blocker.
134. The pharmaceutical safety dosage fonn of claim 128 wherein said sympathomimetic comprises an amphetamine.
59
135. The phannaceutical safety dosage form of claim 134 wherein said amphetamine is methamphetamine, amphetamine, dextroamphetamine, derivatives thereof, or combinations thereof.
136. The pharmaceutical safety dosage form of claim 134 wherein said antagonist further comprises an adrenergic beta blocker.
137. The pharmaceutical safety dosage form of claim 136 wherein said adrenergic beta blocker is propranolol, atenolol, metoprolol, derivatives thereof, or combinations thereof.
138. The pharmaceutical safety dosage form of claim 118 wherein said pharmaceutical comprises a blood pressure-lowering medication.
139. The pharmaceutical safety dosage form of claim 138 wherein said blood pressure- lowering medication is an adrenergic beta blocker, a calcium channel blocker, or an ACE inhibitor.
140. The pharmaceutical safety dosage form of claim 139 wherein said blood pressure- lowering medication is propranolol, metoprolol, nifedipine, diltiazem, nisoldipine, timolol maleate, derivatives thereof, or combinations thereof.
141. The pharmaceutical safety dosage foπn of claim 138 wherein said antagonist further comprises a sympathomimetic.
142. The pharmaceutical safety dosage form of claim 141 wherein said sympathomimetic is dopamine, epinepherine, derivatives thereof, or combinations thereof.
60
143. The pharmaceutical safety dosage form of claim 118 wherein said pharmaceutical comprises a hypoglycemic agent.
144. The pharmaceutical safety dosage form of claim 143 wherein said hypoglycemic agent is insulin, metformin, glipizide, glyburide, derivatives thereof, or combinations thereof.
145. The pharmaceutical safety dosage form of claim 143 wherein said antagonist further comprises a hyperglycemic agent.
146. The pharmaceutical safety dosage form of claim 145 wherein said hyperglycemic agent is epinepherine, glucagon, derivatives thereof, or combinations thereof.
147. A pharmaceutical safety dosage foπn comprising a pharmaceutical in a first form adjacent to an antagonist for said pharmaceutical in a second form wherein said antagonist comprises an emetic agent and has significant bioavailability only when said pharmaceutical safety dosage form is disrupted.
148. The pharmaceutical safety dosage of claim 147 wherein said first form is time-release, or said second fonn comprises an insoluble coating, or both.
149. The pharmaceutical safety dosage form of claim 147 wherein said first form is substantially layered over said second form.
150. The phaπnaceutical safety dosage foπn of claim 147 wherein said second form is substantially layered over said first form.
61
151. The pharmaceutical safety dosage form of claim 147 wherein said bioavailability occurs upon mechanical disruption.
I
152. The pharmaceutical safety dosage foπn of claim 147 wherein said bioavailability occurs upon extraction by a chemical.
153. The pharmaceutical safety dosage fonn of claim 147 adapted to be administered orally.
154. The pharmaceutical safety dosage form of claim 147 adapted to be administered rectally, parenterally, vaginally, transdermally, intranasally, or via aerosol.
155. (Canceled)
156. The pharmaceutical safety dosage fonn of claim 147 wherein said emetic agent is ipecac or derivatives thereof.
157. The pharmaceutical safety dosage fonn of claim 147 wherein said phaπnaceutical comprises a narcotic.
158. The pharmaceutical safety dosage form of claim 157 wherein said narcotic is codeine, oxycodone, propoxyphene, pentazocine, derivatives thereof, or combinations thereof.
159. The phannaceutical safety dosage fonn of claim 157 wherein said antagonist further comprises naloxone, nalmefene, derivatives thereof, or combinations thereof.
160. The pharmaceutical safety dosage foπn of claim 147 wherein said pharmaceutical comprises a sympathomimetic.
62
161. The pharmaceutical safety dosage form of claim 160 further comprising an antihistamine.
162. The phannaceutical safety dosage foπn of claim 161 wherein said sympathomimetic is pseudoephedrine HCl or derivatives thereof, and said antihistamine is cetirizine HCl, fexofenadine HCl, derivatives thereof, or combinations thereof.
163. The pharmaceutical safety dosage form of claim 161 wherein said antagonist further comprises an adrenergic beta blocker.
164. The pharmaceutical safety dosage form of claim 160 wherein said sympathomimetic comprises methylphenidate.
165. The pharmaceutical safety dosage form of claim 164 wherein said antagonist further comprises an adrenergic beta blocker.
166. The pharmaceutical safety dosage fonn of claim 160 wherein said sympathomimetic comprises an amphetamine.
167. The pharmaceutical safety dosage form of claim 166 wherein said amphetamine is methamphetamine, amphetamine, dextroamphetamine, derivatives thereof, or combinations thereof.
168. The pharmaceutical safety dosage form of claim 166 wherein said antagonist further comprises an adrenergic beta blocker.
63
169. The pharmaceutical safety dosage form of claim 168 wherein said adrenergic beta blocker is propranolol, atenolol, metoprolol, derivatives thereof, or combinations thereof.
170. The pharmaceutical safety dosage foπn of claim 147 wherein said phannaceutical comprises a blood pressure-lowering medication.
171. The pharmaceutical safety dosage foπn of claim 170 wherein said blood pressure- lowering medication is an adrenergic beta blocker, a calcium channel blocker, or an ACE inhibitor.
172. The pharmaceutical safety dosage form of claim 171 wherein said blood pressure- lowering medication is propranolol, metoprolol, nifedipine, diltiazem, nisoldipine, timolol maleate, derivatives thereof, or combinations thereof.
173. The pharmaceutical safety dosage form of claim 170 wherein said antagonist further comprises a sympathomimetic.
174. The pharmaceutical safety dosage fonn of claim 173 wherein said sympathomimetic is dopamine, epinepherine, derivatives thereof, or combinations thereof.
175. The pharmaceutical safety dosage form of claim 147 wherein said pharmaceutical comprises a hypoglycemic agent.
176. The pharmaceutical safety dosage form of claim 175 wherein said hypoglycemic agent is insulin, metformin, glipizide, derivatives thereof, or combinations thereof.
64
177. The pharmaceutical safety dosage form of claim 175 wherein said antagomst further comprises a hyperglycemic agent.
178. The pharmaceutical safety dosage foπn of claim 177 wherein said hyperglycemic agent is epinepherine, glucagon, derivatives thereof, or combinations thereof.
179. A method of administering a pharmaceutical comprising: providing a pharmaceutical safety dosage form comprising a pharmaceutical in a first fonn, said first fonn providing a prescribed bioavailability; and providing an antagonist for said pharmaceutical in a second form, said antagonist comprising an emetic agent and said second form providing insignificant bioavailability when administered; and wherein disruption to said phaπnaceutical safety dosage form may result in significant bioavailability of said antagonist.
180. The method of claim 179 wherein said significant bioavailability occurs upon mechanical disruption.
181. The method of claim 179 wherein said significant bioavailability occurs upon extraction by a chemical.
182. The method of claim 179 wherein said pharmaceutical safety dosage form is adapted to be administered orally.
183. The method of claim 179 wherein said pharmaceutical safety dosage form is adapted to be administered rectally, parenterally, vaginally, transdermally, intranasally, or via aerosol.
65
184. (Canceled)
185. The method of claim 179 wherein said emetic agent is ipecac or derivatives thereof.
186. The method of claim 179 wherein said pharmaceutical comprises a narcotic.
187. The method of claim 186 wherein said narcotic is codeine, oxycodone, propoxyphene, pentazocine, derivatives thereof, or combinations thereof.
188. The method of claim 186 wherein said antagonist further comprises naloxone, nalmefene, derivatives thereof, or combinations thereof.
189. The method of claim 179 wherein said pharmaceutical comprises a sympathomimetic.
190. The method of claim 189 wherein said pharmaceutical safety dosage form further comprises an antihistamine.
191. The method of claim 190 wherein said sympathomimetic is pseudoephedrine HCl or derivatives thereof, and said antihistamine is cetirizine HCl, fexofenadine HCl, derivatives thereof, or combinations thereof.
192. The method of claim 190 wherein said antagonist further comprises an adrenergic beta blocker.
193. The method of claim 189 wherem said sympathomimetic comprises methylphenidate.
66
194. The method of claim 193 wherein said antagonist further comprises an adrenergic beta blocker.
195. The method of claim 189 wherein said sympathomimetic comprises an amphetamine.
196. The method of claim 195 wherein said amphetamine is methamphetamine, amphetamine, dextroamphetamine, derivatives thereof, or combinations thereof.
197. The method of claim 196 wherein said antagonist further comprises an adrenergic beta blocker.
198. The method of claim 197 wherein said adrenergic beta blocker is propranolol, atenolol, metoprolol, derivatives thereof, or combinations thereof.
199. The method of claim 179 wherein said pharmaceutical comprises a blood pressure- lowering medication.
200. The method of claim 199 wherein said blood pressure-lowering medication is an adrenergic beta blocker, a calcium channel blocker, or an ACE inhibitor.
201. The method of claim 200 wherein said blood pressure-lowering medication is propranolol, metoprolol, nifedipine, diltiazem, nisoldipine, timolol maleate, derivatives thereof, or combinations thereof.
202. The method of claim 199 wherein said antagonist further comprises a sympathomimetic.
67
203. The method of claim 202 wherein said sympathomimetic is dopamine, epinepherine, derivatives thereof, or combinations thereof.
204. The method of claim 179 wherein said pharmaceutical comprises a hypoglycemic agent.
205. The method of claim 204 wherein said hypoglycemic agent is insulin, metformin, glipizide, glyburide, derivatives thereof, or combinations thereof.
206. The method of claim 204 wherein said antagomst further comprises a hyperglycemic agent.
207. The method of claim 206 wherein said hyperglycemic agent is epinepherine, glucagon, derivatives thereof, or combinations thereof.
208. A method of delivering a drug to a patient comprising placing said drug into a pharmaceutical safety dosage foπn further comprising an antagonist for said drug, said antagonist comprising an emetic agent and being insubstantially bioavailable when said dosage form is not disrupted; and administering said safety dosage form to the patient.
209. (Canceled)
210. The method of claim 208 wherein said emetic agent is ipecac or derivatives thereof.
211. A method of delivering a narcotic to a patient comprising placing said narcotic into a pharmaceutical safety dosage form further comprising a narcotic antagonist and an emetic agent,
68 said narcotic antagonist and said emetic agent being insubstantially bioavailable when said dosage form is not disrupted; and administering said safety dosage form to the patient.
212. The method of claim 211 wherein said narcotic is codeine, oxycodone, propoxyphene, pentazocine, derivatives thereof, or combinations thereof.
213. The method of claim 211 wherein said antagonist further comprises naloxone, nalmefene, derivatives thereof, or combinations thereof.
214. A method of delivering a sympathomimetic to a patient comprising placing said sympathomimetic into a pharmaceutical safety dosage foπn comprising an adrenergic beta blocker, said adrenergic beta blocker being insubstantially bioavailable when said dosage form is not disrupted; and administering said safety dosage form to the patient.
215. The method of claim 214 further delivering an antihistamine along with said sympathomimetic.
216. The method of claim 215 wherein said sympathomimetic and said antihistamine are cetirizine HCl/pseudoephedrine HCl, fexofenadine HCl/pseudoephedrine HCl, derivatives thereof, or combinations thereof.
217. The method of claim 214 wherein said sympathomimetic comprises methylphenidate.
218. The method of claim 214 wherein said sympathomimetic comprises an amphetamine.
69
219. The method of claim 218 wherein said amphetamine is methamphetamine, amphetamine, dextroamphetamine, derivatives thereof, or combinations thereof.
220. The method of claim 219 wherein said adrenergic beta blocker is propranolol, atenolol, metoprolol, derivatives thereof, or combinations thereof.
221. A method of delivering a blood pressure-lowering medication to a patient comprising placing said blood pressure-lowering medication into a pharmaceutical safety dosage form comprising a sympathomimetic, said sympathomimetic being insubstantially bioavailable when said dosage form is not disrupted; and administering said safety dosage form to the patient.
222. The method of claim 221 wherein said blood pressure-lowering medication is an adrenergic beta blocker, a calcium channel blocker, or an ACE inhibitor.
223. The method of claim 222 wherein said blood pressure-lowering medication is propranolol, metoprolol, nifedipine, diltiazem, nisoldipine, timolol maleate, derivatives thereof, or combinations thereof.
224. The method of claim 221 wherein said sympathomimetic is dopamine, epinepherine, derivatives thereof, or combinations thereof.
225. A method of delivering a hypoglycemic agent to a patient comprising placing said hypoglycemic agent into a pharmaceutical safety dosage form comprising a hyperglycemic agent, said hyperglycemic agent being insubstantially bioavailable when said dosage form is not disrupted; and administering said safety dosage form to the patient.
70
226. The method of claim 225 wherein said hypoglycemic agent is insulin, metformin, glipizide, glyburide, derivatives thereof, or combinations thereof.
227. The method of claim 225 wherein said hyperglycemic agent is epinepherine, glucagon, derivatives thereof, or combinations thereof.
228. A method of making a pharmaceutical safety dosage form comprising a phannaceutical and an antagonist for said phaπnaceutical wherein said antagonist comprises an emetic agent that has significant bioavailability only when said pharmaceutical safety dosage form is disrupted.
229. The method of claim 214 wherein said antagonist comprises an emetic agent.
230. The method of claim 221 wherein said antagonist comprises an emetic agent.
231. The method of claim 225 wherein said antagonist comprises an emetic agent.
232. A pharmaceutical safety dosage form comprising a sympathomimetic pharmaceutical and an antagonist for said phannaceutical wherein said antagonist has significant bioavailability only when said phaπnaceutical safety dosage fonn is disrupted.
233. The pharmaceutical safety dosage of claim 232 wherein said pharmaceutical is adapted for time-release, or said antagonist comprises an insoluble coating, or both.
234. The phaπnaceutical safety dosage fonn of claim 232 wherein said bioavailability occurs upon mechanical disruption.
71
235. The pharmaceutical safety dosage form of claim 232 wherein said bioavailability occurs upon extraction by a chemical.
236. The phaπnaceutical safety dosage foπn of claim 232 adapted to be administered orally.
237. The pharmaceutical safety dosage form of claim 232 adapted to be administered rectally, parenterally, vaginally, transdermally, intranasally, or via aerosol.
238. The pharmaceutical safety dosage form of claim 232 further comprising an antihistamine.
239. The pharmaceutical safety dosage form of claim 238 wherein said sympathomimetic is pseudoephedrine HCl or derivatives thereof, and said antihistamine is cetirizine HCl, fexofenadine HCl, derivatives thereof, or combinations thereof.
240. The pharmaceutical safety dosage fonn of claim 238 wherein said antagonist comprises an adrenergic beta blocker.
241. The pharmaceutical safety dosage form of claim 232 wherein said sympathomimetic comprises methylphenidate.
242. The pharmaceutical safety dosage form of claim 241 wherein said antagonist comprises an adrenergic beta blocker.
243. The pharmaceutical safety dosage form of claim 232 wherein said sympathomimetic comprises an amphetamine.
72
244. The pharmaceutical safety dosage form of claim 243 wherein said amphetamine is methamphetamine, amphetamine, dextroamphetamine, derivatives thereof, or ' combinations thereof.
245. The pharmaceutical safety dosage form of claim 244 wherein said antagonist comprises an adrenergic beta blocker.
246. The pharmaceutical safety dosage form of claim 245 wherein said adrenergic beta blocker is propranolol, atenolol, metoprolol, derivatives thereof, or combinations thereof.
247. The pharmaceutical safety dosage form of claim 232 wherein said sympathomimetic phannaceutical is contained within a first microdosage fonn, said first microdosage form being adapted for release of said sympathomimetic pharmaceutical within a patient and said antagomst is contained within a second microdosage form, said second microdosage form being substantially insoluble in gastric fluid.
248. The pharmaceutical safety dosage form of claim 247 wherein said sympathomimetic phannaceutical is adapted for time-release, or said second microdosage form comprises a coating which is substantially insoluble in gastric fluid, or both.
249. The pharmaceutical safety dosage fonn of claim 247 wherein said first microdosage form comprises beads, tablets, mini tablets, or combinations thereof; or second microdosage foπns comprises beads, tablets, mini tablets, or combinations thereof; or both.
250. The pharmaceutical safety dosage form of claim 232 wherein said sympathomimetic pharmaceutical is contained within a first plurality of particulated forms, said first particulated
73 forms being adapted for release of said sympathomimetic pharmaceutical within a patient and said antagonist is contained within a second plurality of particulated forms, said second particulated forms being substantially insoluble in gastric fluid.
251. The pharmaceutical safety dosage foπn of claim 250 wherein said sympathomimetic phaπnaceutical is adapted for time-release, or said second plurality of particulated forms comprise a polymorph or a solvate which is substantially insoluble in gastric fluid, or both.
252. The pharmaceutical safety dosage form of claim 251 wherein said first plurality of particulated forms comprises a sustained-release powder.
253. The pharmaceutical safety dosage form of claim 232 wherein said sympathomimetic phannaceutical is contained within a microdosage form, said microdosage fonn being adapted for release of said sympathomimetic pharmaceutical within a patient said antagonist is contained within a plurality of particulated dosage forms, said particulated dosage forms being substantially insoluble in gastric fluid.
254. The pharmaceutical safety dosage fonn of claim 253 wherein said sympathomimetic pharmaceutical is adapted for time-release, or said plurality of particulated forms comprise a polymorph which is substantially insoluble in gastric fluid, or both.
255. The pharmaceutical safety dosage form of claim 253 wherein said microdosage form comprises beads, tablets, mini tablets, or combinations thereof.
256. The pharmaceutical safety dosage form of claim 232 wherein said sympathomimetic pharmaceutical is contained within a plurality of particulated forms, said particulated forms
74 being adapted for release of said sympathomimetic pharmaceutical within a patient and said antagomst is contained within a microdosage form, said microdosage form being substantially insoluble in gastric fluid.
257. The phannaceutical safety dosage fonn of claim 256 wherein said plurality of particulated forms comprise a polymorph which is substantially insoluble in gastric fluid, or said microdosage form comprises a coating which is substantially insoluble in gastric fluid, or both.
258. The pharmaceutical safety dosage fonn of claim 256 wherein said microdosage form comprises beads, tablets, mini tablets, or combinations thereof.
259. The pharmaceutical safety dosage foπn of claim 232 wherein said sympathomimetic pharmaceutical is in a first fonn adjacent to said antagonist, said antagonist being in a second form.
260. The phannaceutical safety dosage of claim 259 wherein said first form is time-release, or said second form comprises an insoluble coating, or both.
261. The pharmaceutical safety dosage form of claim 259 wherein said first form is substantially layered over said second form.
262. The phaπnaceutical safety dosage foπn of claim 259 wherein said second fonn is substantially layered over said first form.
75
263. A pharmaceutical safety dosage fonn comprising a blood pressure-lowering pharmaceutical and an antagonist for said pharmaceutical wherein said antagonist has significant bioavailability only when said phannaceutical safety dosage form is disrupted.
264. The pharmaceutical safety dosage of claim 263 wherein said phaπnaceutical is adapted for time-release, or said antagonist comprises an insoluble coating, or both.
265. The pharmaceutical safety dosage form of claim 263 wherein said bioavailability occurs upon mechanical disruption.
266. The pharmaceutical safety dosage form of claim 263 wherein said bioavailability occurs upon extraction by a chemical.
267. The pharmaceutical safety dosage form of claim 263 adapted to be administered orally.
268. The pharmaceutical safety dosage form of claim 263 adapted to be administered rectally, parenterally, vaginally, transdermally, intranasally, or via aerosol.
269. The pharmaceutical safety dosage foπn of claim 263 wherein said blood pressure- lowering medication is an adrenergic beta blocker, a calcium channel blocker, or an ACE inhibitor.
270. The pharmaceutical safety dosage fonn of claim 269 wherein said blood pressure- lowering medication is propranolol, metoprolol, nifedipine, diltiazem, nisoldipine, timolol maleate, derivatives thereof, or combinations thereof.
76
271. The pharmaceutical safety dosage foπn of claim 263 wherein said antagonist comprises a sympathomimetic.
272. The pharmaceutical safety dosage form of claim 271 wherein said sympathomimetic is dopamine, epinepherine, derivatives thereof, or combinations thereof.
273. The pharmaceutical safety dosage form of claim 263 wherein said hypoglycemic pharmaceutical is contained within a first microdosage fonn, said first microdosage form being adapted for release of said sympathomimetic pharmaceutical within a patient and said antagonist is contained within a second microdosage form, said second microdosage form being substantially insoluble in gastric fluid.
274. The pharmaceutical safety dosage form of claim 273 wherein said hypoglycemic pharmaceutical is adapted for time-release, or said second microdosage form comprises a coating which is substantially insoluble in gastric fluid, or both.
275. The pharmaceutical safety dosage form of claim 273 wherein said first microdosage form comprises beads, tablets, mini tablets, or combinations thereof; or second microdosage forms comprises beads, tablets, mini tablets, or combinations thereof; or both.
276. The pharmaceutical safety dosage form of claim 263 wherein said hypoglycemic pharmaceutical is contained within a first plurality of particulated fonns, said first particulated forms being adapted for release of said hypoglycemic pharmaceutical within a patient and said antagonist is contained within a second plurality of particulated forms, said second particulated forms being substantially insoluble in gastric fluid.
77
277. The pharmaceutical safety dosage form of claim 276 wherein said hypoglycemic pharmaceutical is adapted for time-release, or said second plurality of particulated forms comprise a polymorph or a solvate which is substantially insoluble in gastric fluid, or both.
278. The pharmaceutical safety dosage form of claim 277 wherein said first plurality of particulated fonns comprises a sustained-release powder.
279. The pharmaceutical safety dosage form of claim 263 wherein said hypoglycemic phannaceutical is contained within a microdosage form, said microdosage fonn being adapted for release of said hypoglycemic pharmaceutical within a patient said antagonist is contained within a plurality of particulated dosage forms, said particulated dosage forms being substantially insoluble in gastric fluid.
280. The pharmaceutical safety dosage form of claim 279 wherein said hypoglycemic pharmaceutical is adapted for time-release, or said plurality of particulated forms comprise a polymorph which is substantially insoluble in gastric fluid, or both.
281. The pharmaceutical safety dosage form of claim 279 wherein said microdosage form comprises beads, tablets, mini tablets, or combinations thereof.
282. The pharmaceutical safety dosage form of claim 263 wherein said hypoglycemic pharmaceutical is contained within a plurality of particulated forms, said particulated forms being adapted for release of said hypoglycemic pharmaceutical within a patient and said antagonist is contained within a microdosage form, said microdosage form being substantially insoluble in gastric fluid.
78
283. The phannaceutical safety dosage form of claim 282 wherein said plurality of particulated forms comprise a polymorph which is substantially insoluble in gastric fluid, or said microdosage form comprises a coating which is substantially insoluble in gastric fluid, or both.
284. The pharmaceutical safety dosage foπn of claim 282 wherein said microdosage form comprises beads, tablets, mini tablets, or combinations thereof.
285. The phaπnaceutical safety dosage form of claim 263 wherein said hypoglycemic pharmaceutical is in a first foπn adjacent to said antagomst, said antagonist being in a second fonn.
286. The pharmaceutical safety dosage of claim 285 wherein said first form is time-release, or said second form comprises an insoluble coating, or both.
287. The pharmaceutical safety dosage fonn of claim 285 wherein said first form is substantially layered over said second form.
288. The pharmaceutical safety dosage form of claim 285 wherein said second form is substantially layered over said first form.
289. A pharmaceutical safety dosage form comprising a hypoglycemic phaπnaceutical and an antagonist for said pharmaceutical wherein said antagonist has significant bioavailability only when said pharmaceutical safety dosage form is disrupted.
290. The pharmaceutical safety dosage of claim 289 wherein said phannaceutical is adapted for time-release, or said antagonist comprises an insoluble coating, or both.
79
291. The pharmaceutical safety dosage form of claim 289 wherein said bioavailability occurs upon mechanical disruption.
292. The phaπnaceutical safety dosage foπn of claim 289 wherein said bioavailability occurs upon extraction by a chemical.
293. The pharmaceutical safety dosage fonn of claim 289 adapted to be administered orally.
294. The pharmaceutical safety dosage form of claim 289 adapted to be administered rectally, parenterally, vaginally, transdermally, intranasally, or via aerosol.
295. The phaπnaceutical safety dosage foπn of claim 289 wherein said hypoglycemic agent is insulin, metformin, glipizide, glyburide, derivatives thereof, or combinations thereof.
296. The pharmaceutical safety dosage foπn of claim 289 wherein said antagonist comprises a hyperglycemic agent.
297. The pharmaceutical safety dosage form of claim 289 wherein said hypoglycemic pharmaceutical is contained within a first microdosage form, said first microdosage form being adapted for release of said sympathomimetic pharmaceutical within a patient and said antagonist is contained within a second microdosage form, said second microdosage form being substantially insoluble in gastric fluid.
298. The pharmaceutical safety dosage form of claim 297 wherein said hypoglycemic pharmaceutical is adapted for time-release, or said second microdosage form comprises a coating which is substantially insoluble in gastric fluid, or both.
80
299. The phaπnaceutical safety dosage form of claim 297 wherein said first microdosage form comprises beads, tablets, mini tablets, or combinations thereof; or second microdosage forms comprises beads, tablets, mini tablets, or combinations thereof; or both.
300. The phannaceutical safety dosage fonn of claim 289 wherein said hypoglycemic pharmaceutical is contained within a first plurality of particulated forms, said first particulated fonns being adapted for release of said hypoglycemic pharmaceutical within a patient and said antagonist is contained within a second plurality of particulated forms, said second particulated foπns being substantially insoluble in gastric fluid.
301. The phaπnaceutical safety dosage form of claim 300 wherein said hypoglycemic pharmaceutical is adapted for time-release, or said second plurality of particulated foπns comprise a polymorph or a solvate which is substantially insoluble in gastric fluid, or both.
302. The phannaceutical safety dosage fonn of claim 301 wherein said first pluι-ality of particulated forms comprises a sustained-release powder.
303. The pharmaceutical safety dosage fonn of claim 289 wherein said hypoglycemic pharmaceutical is contained within a microdosage form, said microdosage form being adapted for release of said hypoglycemic pharmaceutical within a patient said antagonist is contained within a plurality of particulated dosage forms, said particulated dosage forms being substantially insoluble in gastric fluid.
81
304. The phannaceutical safety dosage foπn of claim 303 wherein said hypoglycemic pharmaceutical is adapted for time-release, or said plurality of particulated forms comprise a polymorph which is substantially insoluble in gastric fluid, or both.
305. The phannaceutical safety dosage form of claim 303 wherein said microdosage form comprises beads, tablets, mini tablets, or combinations thereof.
306. , The pharmaceutical safety dosage form of claim 289 wherein said hypoglycemic pharmaceutical is contained within a plurality of particulated forms, said particulated forms being adapted for release of said hypoglycemic pharmaceutical within a patient and said antagonist is contained within a microdosage form, said microdosage form being substantially insoluble in gastric fluid.
307. The phannaceutical safety dosage fonn of claim 306 wherein said plurality of particulated forms comprise a polymorph which is substantially insoluble in gastric fluid, or said microdosage form comprises a coating which is substantially insoluble in gastric fluid, or both.
308. The pharmaceutical safety dosage form of claim 306 wherein said microdosage form comprises beads, tablets, mini tablets, or combinations thereof.
309. The pharmaceutical safety dosage form of claim 289 wherein said hypoglycemic phaπnaceutical is in a first form adjacent to said antagonist, said antagonist being in a second fonn.
310. The phannaceutical safety dosage of claim 309 wherein said first form is time-release, or said second form comprises an insoluble coating, or both.
82
311. The phannaceutical safety dosage form of claim 309 wherein said first form is substantially layered over said second form.
312. The pharmaceutical safety dosage form of claim 309 wherein said second form is substantially layered over said first form.
313. A pharmaceutical safety dosage form comprising a pharmaceutical which is substantially free of a narcotic and an antagonist for said pharmaceutical wherein said antagonist has significant bioavailability only when said pharmaceutical safety dosage form is disrupted.
314. A method of administering a pharmaceutical comprising providing a pharmaceutical safety dosage form comprising a pharmaceutical in a first form, said phaπnaceutical being substantially free of a narcotic and said first form providing a prescribed bioavailability; and providing an antagonist for said pharmaceutical in a second form, said second form providing insignificant bioavailability when administered; and wherein disruption to said pharmaceutical safety dosage fonn may result in significant bioavailability of said antagonist.
315. A method of making a pharmaceutical safety dosage form comprising a pharmaceutical which is substantially free of a narcotic and an antagonist for said pharmaceutical wherein said antagonist has significant bioavailability only when said pharmaceutical safety dosage form is disrupted.
83
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CA2505661C (en) 2011-06-14
US20030124061A1 (en) 2003-07-03
AU2003299826A1 (en) 2004-08-10
US7524515B2 (en) 2009-04-28
EP1581188A1 (en) 2005-10-05
CA2505661A1 (en) 2004-07-29
EP1581188A4 (en) 2006-04-05
US7919120B2 (en) 2011-04-05
TWI265812B (en) 2006-11-11
JP2006514067A (en) 2006-04-27
US20090175950A1 (en) 2009-07-09
CA2735280A1 (en) 2004-07-29
TW200505506A (en) 2005-02-16

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