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Combination dosage form of a mu opioid receptor antagonist and an opioid agent

a technology of opioid receptor and combination dosage form, which is applied in the direction of heterocyclic compound active ingredients, drug compositions, coatings, etc., can solve the problems of insufficient stability of amorphous axelopran for use in drug products, and achieve the effect of improving the symptoms of opioid-induced constipation, without affecting pharmacokinetic characteristics, and without affecting amorphous axelopran

Inactive Publication Date: 2016-10-06
THERAVANCE BIOPHARMA R&D IP LLC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The patent describes a way to make medication that combines two different drugs, without affecting their release patterns or abuse-deterrent properties. This is useful for creating products that offer both fast pain relief and other benefits, like preventing constipation. The medication involves a combination of an opioid painkiller and a drug called axelopran. This new combination could be a useful treatment for opioid-induced constipation.

Problems solved by technology

Axelopran has been shown to be stable as the crystalline sulfate salt while amorphous axelopran is known to be insufficiently stable for use in a drug product.

Method used

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  • Combination dosage form of a mu opioid receptor antagonist and an opioid agent
  • Combination dosage form of a mu opioid receptor antagonist and an opioid agent
  • Combination dosage form of a mu opioid receptor antagonist and an opioid agent

Examples

Experimental program
Comparison scheme
Effect test

example 1

Spray Coating Process

[0102]A Thomas Compu-Lab 19 inch pan coater was used to prepare the combination dosage forms of Examples 2 and 3. Processing parameters optimized for coating performance and efficiency are summarized in Table 1.

TABLE 1Processing ParametersSet ISet IIExhaust Temp (° C.) 40a 40aSolution Spray Rate (g / mL)1513Atomizing Air Pressure (psi) 35b 35bPan Speed (rpm)1515Air Flow Rate (scfm)170 170 Inlet Temp (° C.)6565Gun to Bed Distance (inches) 7 7aRange: 35-50bRange: 25-45

example 2

Preparation of Combination Dosage Form of Axelopran (10 mg) and Oxycodone Hydrochloride (20 mg)

[0103]Placebo cores were manufactured to match the OxyContin® tablets and were used as the main load of the substrate for the coating.

[0104](a) Preparation of Subcoat

[0105]To prepare the coating solution, polyvinyl alcohol (40 g) was added to heated purified water USP. The mixture was stirred and heated to dissolution and then polyethylene glycol 3350 (80 g) was added and the mixture was stirred to dissolution. Purified water USP was added with stirring to provide a solution of approximately 10% solid content (i.e., non-aqueous content; the solid content is not in solid form).

[0106]A total of approximately 4 kg of placebo cores and a small number of OxyContin® tablets were spray coated with the subcoat solution according to the processing parameters of Table I Set Ito achieve an approximate 3% weight gain of the sub-coat composition listed in Table 2.

TABLE 2Sub-coat Formulation Composition...

example 3

Preparation of Combination Dosage Form of Axelopran (10 mg) and Oxymorphone Hydrochloride (20 mg)

[0110]Placebo cores were manufactured to match the Opana® ER tablets and were used as the main load of the substrate for the coating.

[0111](a) Preparation of Subcoat

[0112]A subcoat coating solution was prepared as in Example 2(a). A total of approximately 4 kg of placebo cores and a small number of Opana® ER tablets were spray coated according to the processing parameters of Table I Set II resulting in an approximate 3% weight gain of the sub-coat composition listed in Table 2.

[0113](b) Preparation of Active Coating Layer

[0114]Coating solutions for the two formulations of Table 3 were prepared as described in Example 2(a). Upon completion of the sub-coating, the sub-coated placebo cores and opioid tablets were retained in the pan coater and further spray coated with the active coating solutions according to the processing parameters of Table 1 Set I to achieve the target weight gain. Coa...

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Abstract

The invention provides a solid composition of the peripheral mu opioid antagonist axelopran and a combination dosage form of the mu opioid antagonist axelopran sulfate in an immediate release form and an opioid analgesic agent which may be in an extended release, sustained release, modified release, or controlled release form and methods of preparing such a combination dosage form.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application claims the benefit of U.S. Provisional Application No. 62 / 141,981, filed on Apr. 02, 2015 the disclosure of which is incorporated herein by reference in its entirety.BACKGROUND OF THE INVENTION[0002]1. Field of the Invention[0003]The invention is directed to a solid composition of a peripheral mu opioid receptor antagonist and to a combination of the mu opioid receptor antagonist composition and an opioid analgesic agent. In particular, the invention is directed to a unit dosage form in which the mu opioid receptor antagonist is in an immediate release form and the opioid analgesic agent may be in an extended release, sustained release, modified release, or controlled release form and to methods of preparing such a unit dosage form.[0004]2. State of the Art[0005]Compounds which function as agonists at opioid receptors, of which oxycodone, hydrocodone, morphine, and oxymorphone are common examples, are the mainstays of ana...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K31/46A61K31/485A61K9/28
CPCA61K31/46A61K9/2853A61K9/2893A61K9/284A61K31/485A61K9/282A61K9/209A61K31/439A61K2300/00A61P25/04A61P43/00
Inventor LI, SHAOLINGLEUNG, MANSHIUZHANG, HAOTHALLADI, VENKAT R.MO, YUN
Owner THERAVANCE BIOPHARMA R&D IP LLC