MYLAN PHARMS. INC. EXHIBIT 1045 PAGE 1
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`thwe figures would graphically portray solubility relations
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`placing them in proximity to a high 54, high 5,, and high
`6:. region. Acetone is an exception to this situation and
`represents a deviation. Its low molecular volume may
`be important here. The water associated with the hydrated
`salts alters the solubility parameter of the liquid as soon
`as the hydrated salt starts dissolving. This adds consider-
`able confusion to trying to characterize these salts more
`accurately in terms of the solubility parameter. An out-
`standing example of this is the two-phase system found
`by dissolving Ni(N0al-2-5H20 in acetonitrile, a solvent
`which is completely miscible in water otherwise.
`The solubility region for Mg(NO:rl2‘6l-I20 is plotted
`in Figures 8, 9, and 10. Slight additions or deletions to
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`I2
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`5:0
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`02468lO|2l4l6|B
`5
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`Figure 8. Region of Interaction for Mg(NO3)2-6HgO
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`0
`8p
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`7
`6
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`5
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`7
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`8
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`5::
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`9
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`I0
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`II
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`I2
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`I3
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`Figure 10. Region of inleruclion for Mg(NO3)2-6H20
`for the other salts. Here again,
`the center and radius
`are indicative of the symmetry of the plots and are I101
`to be construed as accurate representations of any proper-
`ties of the salt.
`Attempts were made to dissolve a number of solutes
`predictably, using the combination of an organic non-
`solvent and a salt,
`in spite of the confusion added by
`the hydration. The general approach is to visualize the
`approximate placement of the salt
`in the system arid
`to locate an organic nonsolvent which dissolved the salt.
`at the same time being located such that the resulting
`average placement would be within the solubility region
`for the solute. Several systems conforming to this Plan
`'
`“
`be
`1”
`dissolved the solute tested’ but m a “um I 0
`cases
`the result was only a decided swelling or partial solubility
`of the solute. This may be related to the difliculty in
`estimating the approximate placement of the salts, and
`because water, and undoubtedly other factors.
`is also
`important. Systems where solubility was found but could
`not be attributed to the elfect of the added hydrated
`water alone include: zein soluble in a 10% solutim! Oi
`calcium nitrate in butyrolactone and in a 20% solution
`of magnesium nitrate in 1-butanol; and milled wood 551119
`soluble in a 10% solution of stannous chloride in Pmpylem
`carbonate.
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`A similar situation prevails in the case cited by B0173”
`(1968), where a 15% solution of calcium chloride in metha-
`nol dissolved Nylon 66.
`With regard to another inorganic system. 8U1fU1'i€ acid
`appears to behave as though it been solubility parameter
`composed of a high 5;, low 5,, and high fir
`in Situatiflns
`where it does not rwct with the solute.
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`Special Cases
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`Any general theory of solubility must be able to account
`for several special cases if it is to be completei}'_ _V8i1d-
`The data already presented show that the solubility Of
`a material
`in mixed nonsolvsnte can be interpreted
`terms of the solubility parameter. Experience and experi-
`_ ment have shown that solubility parameter regions become
`smaller with increasms 90111119 0090913390“ ‘ml “‘°l°°“1‘“
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`0
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`6
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`5
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`6
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`7
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`5
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`9
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`in?
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`5:!
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`Figure 9. Region of interaction for Mg(N0:r)2°6H20
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`I0
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`IIIEC PRODUCT RESEARCH AND DEVEI.0I'MINT
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