Methods of producing stabilized solid dosage pharmaceutical compositions containing morphinans

A solid dosage form, morphinan technology, applied in the field of preparation of morphinan protective granules, can solve the problem of not being very effective

Inactive Publication Date: 2013-11-20
MALLINCKRODT INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

For solid dosage forms of morphinan compositions, the introduction of additional antioxidant excipients or pH-lowering excipients to prevent degradation of the morphinan, especially when formulated in solid dosage forms, has also been less effective to date

Method used

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  • Methods of producing stabilized solid dosage pharmaceutical compositions containing morphinans
  • Methods of producing stabilized solid dosage pharmaceutical compositions containing morphinans
  • Methods of producing stabilized solid dosage pharmaceutical compositions containing morphinans

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0137] Example 1: Incorporation of Protected Oxycodone Particles into Bilayer Tablet Compositions

[0138] To demonstrate the feasibility of forming and incorporating protected morphinan particles into solid dosage forms, the following experiments were performed.

[0139] Powdered oxycodone hydrochloride, microcrystalline cellulose (MCC) and citric acid powder (antioxidant) were mixed together and charged to a high shear granulator. Will contain pregelatinized starch (PGS) and Na 2 An aqueous solution of EDTA (antioxidant) is sprayed to a high-speed granulator to form wet granules. The wet granules are then dried until less than about 2% water remains in the granules. The dried granules have a particle size in the range of about 100-300 μm. The composition of the protected oxycodone particles is summarized in Table 3:

[0140] Table 3: Composition of protected oxycodone particles

[0141]

[0142] The oxycodone protected granules are divided into two groups which wil...

Embodiment 2

[0150] Example 2: Evaluation of Oxidative Stability of Bilayer Tablet Compositions

[0151] To assess the effect of incorporation of protected particulate forms of morphinans into solid dosage form therapeutic compositions on the oxidative stability of the compositions, the following experiments were performed.

[0152] Unprotected bilayer tablets were formed using a method similar to that described in Example 1, except that powdered oxycodone hydrochloride, rather than protected oxycodone granules, was incorporated into IR and SR formed using fluidized bed granulation equipment. in particles. Protected bilayer tablets formed using the protected oxycodone granules described in Example 1 were also obtained. The composition of the unprotected bilayer tablet was similar to that of the protected bilayer tablet, and the overall oxycodone content of the two bilayer tablet formulations was comparable, but the unprotected bilayer tablet lacked antioxidant excipients and oxycodone p...

Embodiment 3

[0159] Example 3: Effect of Particle Composition on Oxidative Stability

[0160] To assess the effect of various particle compositions on the oxidative stability of morphinans encapsulated in the particles, the following experiments were performed.

[0161] Granules comprising a combination of oxycodone and various excipients were formed using a method similar to Example 1 . The specific composition of the particles is summarized in Table 7:

[0162] Table 7: Composition of IR and SR particles

[0163]

[0164] For granule compositions 1, 2 and 3, HPC and EDTA were dissolved in the granulation solution and applied to the dry mixture of the remaining ingredients. For granule compositions 5 and 6, PGS and EDTA were dissolved in the granulation solution and applied to the dry mixture of the remaining ingredients.

[0165] The resulting granules were stored under accelerated stability conditions at 40°C and 75% relative humidity for 4 weeks. Granule samples were taken imm...

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Abstract

Methods for producing stabilized solid dosage form pharmaceutical compositions are provided. In particular, methods for preparing protected granules containing morphinans, and solid dosage form pharmaceutical compositions produced using the morphinan-protected granules are provided.

Description

[0001] Cross References to Related Applications [0002] This application is a continuation-in-part of U.S. Application Serial No. 12 / 973,962, filed December 21, 2010, which claims priority to U.S. Provisional Application 61 / 284,651, filed December 22, 2009, each in its entirety at This is incorporated by reference. technical field [0003] The present invention relates to a process for the preparation of stable solid dosage forms of morphinan pharmaceutical compositions. In particular, the present invention relates to a process for the preparation of morphinan-protected particles which can be incorporated into solid dosage forms of morphinan pharmaceutical compositions. Background technique [0004] Minimizing the degradation of active pharmaceutical ingredients (APIs) in pharmaceutical compositions is an ongoing challenge in research and development. Degradation can occur from physical or chemical instability of the API in the pharmaceutical composition with incompatibl...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/20A61K9/50A61K31/485A61K31/167A61P25/00A61P29/00A61K45/06
CPCA61K9/5042A61K9/2081A61K31/47A61K9/2086A61K31/4375A61K31/445A61K31/439A61K31/4355A61K9/1652A61K9/2031A61K45/06A61K9/2077A61K9/209A61P25/00A61P25/04A61P29/00A61P43/00A61K2300/00A61K31/485
Inventor 朴宰汉T.艾森豪尔A.达纳拉詹V.K.格普塔S.奥弗霍尔特
Owner MALLINCKRODT INC
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