Patent Grant
7534888
Oxycodone (4,5-epoxy-14-hydroxy-3-methoxy-17-methylmorphinan-6-one) is a well-known narcotic analgesic. The hydrochloride salt is commercially used in numerous products, such as Oxycontin, Tylox, and Percocet.
The present invention is directed to nine novel forms of oxycodone.HCl. These are identified herein as forms A and I-VIII. The known form of the oxycodone.HCl is referred to hereinafter as oxycodone.
All nine forms are derived directly or indirectly from oxycodone and are characterized by physical data, most notable by their X-ray powder diffraction patterns expressed in terms of °2θ and the relative intensities of the X-ray diffraction peaks.
One aspect of the invention is the novel forms of oxycodone. Another aspect is processes to make these novel forms. Since these forms are essentially equally effective as oxycodone itself, they can be used instead of or in combination with oxycodone for its pharmacological effects. The novel forms may be produced and used as the pure form, or the forms may be produced and used in combination with other forms and/or oxycodone. Another aspect of the invention is compositions comprising therapeutically effective amounts of one or more of these novel forms, optionally in combination with oxycodone, and pharmaceutically acceptable carriers therefor. Another aspect is a method of providing an analgesic effect to a mammal, preferably a human, in need thereof which comprises administering to said mammal a therapeutic amount of one or more of a novel form of the invention, optionally in combination with oxycodone. Oxycodone, its therapeutic uses and doses ranges, modes of administration, etc. are all well known in the art.
By pure is meant that each form of the invention is about 90-100%, preferably 95-100%, more preferably 98-100% (wt./wt.) pure; e.g. free of other oxycodone forms, solvents, and/or other undesirable non-oxycodone impurities. A preferred polymorph of the invention is one which is free of other oxycodone forms, preferably 98-100% free.
The forms of the invention may be produced by a process which comprises:
Another embodiment of the invention is a form of oxycodone made by the process supra, more specifically a form made by a process such as recited in the examples.
Table I summarizes the prominent peaks of the X-ray powder diffraction patterns of each oxycodone form. The relative intensity (R.I.) of each peak is shown, wherein R.I. is the ratio of the height of each peak compared to the highest peak, which is designated as 100%.
The data were generated using either:
Table II summarizes the peaks of the X-ray powder diffraction patterns of each oxycodone form that are either unique (peaks that are not shared with other forms within ±0.20 °2θ) or intense (R.I.≧15).
The invention is further defined by reference to the following examples, which are intended to be illustrative and not limiting.
Oxycodone, 29.8 mg, and 75:25 ethanol/water, 0.8 mL, were combined in a vial, which was sonicated to dissolve the solids. The sample was filtered (0.2 μm nylon filter) and allowed to evaporate uncapped to dryness to yield Form A.
Oxycodone, 50.0 mg, and water, 0.3 mL, were combined in a vial, which was sonicated to dissolve the solids. The sample was filtered (0.2 μm nylon filter) and allowed to evaporate uncapped to dryness to yield Form I.
Oxycodone, 199.4 mg, and 95:5 ethanol/water, 2 mL, were combined in a vial to form a cloudy sample, which was agitated at 60° C. The sample was filtered (0.2 μm nylon filter) and allowed to evaporate very slowly, i.e. covered with foil containing 1 pinhole, to yield Form II.
Oxycodone, 100.5 mg, and ethanol, 1.6 mL, were combined in a vial, which was stirred for approximately 10 min. at 60° C. The sample was filtered (0.2 μm nylon filter) into a clean vial and cooled to 20° C. covered to yield Form III.
Oxycodone, 49.8 mg, and dioxane, 18 mL, were combined in a vial to form a cloudy sample, which was stirred at ambient temperature overnight. The resultant solids were collected by vacuum filtration to yield Form IV.
Oxycodone, 50.0 mg, and 92:8 butanol/water, 3.3 mL, were combined in a vial, which was sonicated to dissolve solids. The sample was filtered (0.2 μm nylon filter) and allowed to evaporate uncapped to dryness to yield Form V.
Oxycodone, 50.8 mg, and 92:8 isopropanol/water, 6 mL, were combined in a vial, which was sonicated to dissolve solids. The sample was filtered (0.2 μm nylon filter) and allowed to evaporate very slowly, i.e. covered with foil containing 1 pinhole, to dryness to yield Form VI.
Oxycodone Form A was heated to 60-120° C. on a variable temperature XRPD for less than 30 min. to yield Form VII.
Oxycodone was heated to 200° C. on a variable temperature XRPD for less than 30 min. to yield Form VIII.
This application claims benefit to U.S. provisional application Ser. No. 60/403,826, filed on Aug. 15, 2002.
| Number | Name | Date | Kind |
|---|---|---|---|
| 5508042 | Oshlack et al. | Apr 1996 | A |
| 5981751 | Mudryk et al. | Nov 1999 | A |
| Number | Date | Country |
|---|---|---|
| 286 431 | Aug 1915 | DE |
| 411 530 | Mar 1925 | DE |
| 0 900 582 | Mar 1999 | EP |
| Number | Date | Country | |
|---|---|---|---|
| 20070197572 A1 | Aug 2007 | US |
| Number | Date | Country | |
|---|---|---|---|
| 60403826 | Aug 2002 | US |
