Treating pain by administering 24 hours opioid formulations exhibiting rapid rise of drug level

a technology of opioids and formulations, applied in the direction of drug compositions, oil/fat/waxes non-active ingredients, microcapsules, etc., can solve the problems of special problems in maintaining analgesic efficacy, insure bioavailability of gastrointestinal fluids, and inability to withstand 24 hours, and achieve rapid rise and greater analgesic efficacy

US20020058050A1Inactive Publication Date: 2002-05-16PURDUE PHARMA LP
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Patent Information

Authority / Receiving Office
US · United States
Patent Type
Applications(United States)
Current Assignee / Owner
Publication Date
2002-05-16
Estimated Expiration
Not applicable · inactive patent

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Abstract

Patients are treated with 24-hour oral sustained release opioid formulations which, upon administration, provide an initially rapid opioid absorption such that the minimum effective analgesic concentration of the opioid is more quickly achieved. These sustained release opioid formulations include an effective amount of at least one retardant material to cause said opioid analgesic to be released at a such a rate as to provide an analgesic effect after oral administration to a human patient for at least about 24 hours, and are characterized by providing an absorption half-life from 1 to about 8 hours. A method of titrating a human patient utilizing these sustained release opioid formulations is also disclosed.
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Description

BACKGROUND OF THE INVENTION

[0001] The present invention relates to bioavailable sustained-released pharmaceutical formulations of analgesic drugs, in particular opioid analgesics, which provide an extended duration of effect when orally administered.

[0002] It is the intent of all sustained-release preparations to provide a longer period of pharmacologic response after the administration of the drug than is ordinarily experienced after the administration of the rapid release dosage forms. Such longer periods of response provide for many inherent therapeutic benefits that are not achieved with corresponding short acting, immediate release preparations. This is especially true in the treatment of cancer patients or other patients in need of treatment for the alleviation of moderate to severe pain, where blood levels of an opioid analgesic medicament must be maintained at a therapeutically effective level to provide pain relief. Unless conventional rapid acting drug therapy in carefully...

Examples

examples 1-2

[0102] In Example 1, morphine sulfate sustained-release beads with a 5% w / w sustained release coating comprising Eudragit.RTM. RS were prepared, including a 10% immediate release morphine sulfate overcoat. In Example 2, morphine sulfate sustained-release beads with an 8% w / w sustained-release coating comprising Eudragit.RTM. RS were prepared, including a 10% immediate release morphine sulfate overcoat.

[0103] Morphine sulfate beads were first manufactured using a rotor processing technique. The formula of the morphine sulfate beads to which the sustained-release coating was applied is set forth in Table 1 below:

1 TABLE 1 Amt / Unit Ingredient (mg) Percent (%) Morphine Sulfate Powder 30 mg 14.3% Lactose Hydrous Impalpable 42.5 mg 20.2% PVP 2.5 mg 1.2% Sugar Beads 18 / 20 125 mg 59.4% Purified Water qs mg -- Opadry Red YS-1-1841 10.5 mg 4.9% Total 210.5 mg 100.0%

[0104] A sustained-release coating was then applied to the morphine sulfate beads. The formula for the sustained release coating ...

example 3

[0167] Beads with a higher loading of morphine sulfate were produced with the use of the powder layering technique in the Glatt Rotor Processor. The formulation of the high load beads is set forth in Table 8 below:

8 TABLE 8 High Load Bead Percent Ingredient mg / unit (%) Morphine Sulfate Powder 30.0 mg 63.3% Lactose 6.0 mg 12.7% Povidone C-30 1.25 mg 2.6% Sugar Beads 7.75 mg 16.4% Opadry 2.37 mg 5.0% Purified Water qs -- Total 47.37 mg 100.0%

[0168] The sustained-release coating comprised an acrylic polymer (i.e., Eudragit.RTM. RL). A HPMC protective coat was also included between the Eudragit layer and the morphine immediate release layer to further enhance stability. The formula of the sustained release coating of Example 1 is set forth in Table 9 below:

9 TABLE 9 Amt / Unit Percent Ingredient (mg) (%) Morphine (high load) base beads 42.63 mg 78.8% Retardant Coating Eudragit RS 30D 2.1 mg 3.9% Eudragit RL 30D 0.05 mg 0.1% Triethyl Citrate 0.45 mg 0.8% Talc 0.85 mg 1.6% Overcoatings Opad...

example 4

[0180] Beads with a higher loading of morphine sulfate were produced with the use of the powder layering technique in the Glatt Rotor Processor. The formulation of the high load beads is set forth in Table 15 below.

15 TABLE 15 High Load Percent Ingredient Bead mg / unit (%) Morphine Sulfate Powder 60.0 mg 56.4% Lactose 12.0 mg 11.3% Eudragit RS30D 4.16 mg 3.9% Povidone C-30 8.31 mg 7.8% Sugar Beads 16.80 mg 15.8% Opadry 5.06 mg 4.8% Purified Water qs -- Total 106.33 mg 100%

[0181] These immediate release base beads were manufactured using the powder layering technique in the Glatt Rotor Processor.

[0182] The sustained release coating comprised an ethylcellulose acrylic polymer (i.e., Aquacoat ECD 30). A HPMC protective coat was also included after the Aquacoat layer to further enhance stability. The formula of the sustained-release coating of Example 1 is set forth in Table 16 below.

16 TABLE 16 Ingredient Amt / Unit (mg) Percent (%) Morphine (high load) 106.33 mg 73.1% based beads Retarda...