DEGRADANT COMPOUNDIN A MEDICAMENT
`
`BACKGROUND
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`[0001] The present invention relates to a degradant formed in a medicamentincluding at
`
`least carbachol and brimonidine, and more specifically to detecting improper storage by
`
`presence of the degradant compound.
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`SUMMARY
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`[0002] According to one embodimentof the present invention, a degradant compoundis
`
`disclosed. The degradant compound developsis in small, tolerable quantities when the
`
`medicamentis at room temperature conditions and increases over time and as the
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`10
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`temperature increases. Detection of the degradant compoundin specific quantities or
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`detection of the degradant compound within a medicamentcan be indicative of detecting
`
`improper storage by presence of the compound. Methods of avoiding a degradation
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`compound formation by storing at specific temperatures below room temperature can also
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`be used.
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`15
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`DETAILED DESCRIPTION
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`[0003]
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`In a medicamentfor application to at least the eye that includesat least a
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`combination of brimonidine and carbachol (Brimochol), a degradant chemical compound
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`forms based on the time in storage and temperature in which the medicamentis stored.
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`[0004] The degradant compound that developsis in small, tolerable quantities when the
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`20
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`medicamentis at room temperature conditions. The degradant compound develops in
`
`much greater quantities when the temperature increases andrises to intolerable levels for a
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`user of the medicament. The degradant compound can serve as a marker for evaluating
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`whether the medicamenthas been stored in the proper environmental conditions over time.
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`[0005] An example of the degradant compoundis shown below and has a chemical name
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`25
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`of 2-((5-bromoquinoxalin-6-yl)amino)-4,5-dihydro-1H-imidazole-1-carboxamide.
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`1 of 6
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`

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`Br
`
`Zo
`
`Z
`
`HN
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`Chemical Formula: C,,H,, BrN,O
`Molecular Weight: 335.17
`
`[0006] A mechanism for the formation of the degradant compound from the brimonidine
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`and carbachol of the medicament is shown below. The degradant compound can be
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`formed by the lens modulation from lipoic acid choline due to the lipoic acid effect on
`
`reducing disulfide bonds.
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`2 of 6
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`

`

`Hyatt
`y
`
`:
`S
`NO FMy
`
`Bei
`ss:
`apenas ie
`x davraandslayed!
`
`
`
`Carbackol
`
`Choice
`
`Degradant
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`[0007] The available 5 monthsof in-lab stability data for Brimochol within medicaments
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`indicates a primary brimonidine degradant compound as shown above and observed in a
`
`brimonidine assay via method TRC-MTH-0066 at RRT=0.9. This degradant compoundis
`
`observed up to 3.3% at 40°C and up to 0.25% at 25°C after 5 months of storage. Table 1
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`showsthe stability data.
`
`
`Time Point
`Storage Conditions
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`25°C 40% RH
`
`40°C NMT 25% RH
`
`5 Months
`
`Initial
`
`0.09%
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`0.09%
`
`
`1 Month
`0.13%
`0.47%
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`2 Months
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`0.15%
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`0.74%
`
`
`3 Months
`0.15%
`1.1%
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`Table 1
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`3 of 6
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`

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`[0008] High resolution mass spectrometric HPLC-MSanalysis indicates the structure of
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`the degradant compound as shown above.
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`[0009] Detection of the degradant compoundin specific quantities or detection of the
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`degradant compound within a medicament can be indicative of detecting improper storage
`
`by presence of the compound; and a methodof avoiding a degradation compound
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`formation by storing at specific temperatures. Testing and detection can take place using
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`various methods.
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`[0010] Accordingly,it is to be understood that the embodiments of the invention herein
`
`described are merely illustrative of the application of the principles of the invention.
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`10
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`Reference herein to details of the illustrated embodimentsis not intendedto limit the
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`scope of the claims, which themselvesrecite those features regarded as essential to the
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`invention.
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`4 of 6
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