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`film to effectuate drying. The matrix from whichthe film is formed mayalso include an
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`Thepresent invention also provides a pharmaceutical composition in the form ofa
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`forms of the pharmaceutical compositions and films of the present invention. The dosage
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`anti-foaming agent will aid in preventing the introduction ofair into a composition, while a
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`BRIEF DESCRIPTION OF THE DRAWINGS
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`Figure 1 showsa side view of a package containing a unit dosage film of the present
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`Figure 2 showsa top view of two adjacently coupled packages containing individual
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`Figure 3 showsa side view of the adjacently coupled packages of Figure 2 arranged in
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`Figure 4 showsa perspective view of a dispenser for dispensing the packaged unit
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`Figure 5 is a schematic view of a roll of coupled unit dose packages of the present
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`Figure 6 is a schematic view of an apparatus suitable for preparation of a pre-mix,
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`Figure 7 is a schematic view of an apparatus suitable for drying the films of the
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`DETAILED DESCRIPTION OF THE INVENTION
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`For the purposes of the present invention the term non-self-aggregating uniform
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`heterogeneity refers to the ability of the films of the present invention, which are formed from
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`as is normally experienced whenfilms are formed by conventional drying methods such as a
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`that will incorporate a single component, such as a polymer, as well as combinations of
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`Page 732
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`Page 732
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`Page 734
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`WO 03/030882
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`13
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`PCT/US02/32575
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`drug particles) sedimentation in non-colloidal applications. One approach provided by the
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`present invention is to balance the density of the particulate (pp,) and the liquid phase (p,) and
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`increase the viscosity of the liquid phase (1). For an isolated particle, Stokes law relates the
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`terminal settling velocity (Vo) of a rigid spherical body of radius(r) in a viscous fluid, as
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`Vo = (28r(Pp - P)/9E
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`Athigh particle concentrations, however, the local particle concentration will affect
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`the local viscosity and density. The viscosity of the suspensionis a strong function ofsolids
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`volumefraction, and particle-particle and particle-liquid interactions will further hinder
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`Stokian analyses has shown that the incorporation of a third phase, dispersed air or
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`nitrogen, for example, promotes suspension stability. Further, increasing the numberof
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`particles leads to a hindered settling effect based on the solids volumefraction. In dilute
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`particle suspensions,the rate of sedimentation, v, can be expressedas:
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`W/V, = 1/1 + K@)
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`where k = a constant, and 9 is the volumefraction of the dispersed phase. More particles
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`suspendedin the liquid phase results in decreased velocity. Particle geometry is also an
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`important factor since the particle dimensionswill affect particle-particle flow interactions.
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`Similarly, the viscosity of the suspension is dependent on the volumefraction of
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`dispersed solids. For dilute suspensions of non-interaction spherical particles, an expression
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`H/o = 1+ 2.50
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`where 1, is the viscosity of the continuous phase and @ is the solids volumefraction. At
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`higher volumefractions, the viscosity of the dispersion can be expressed as
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`W/o = 1+ 2.59 + Cig? + Cop? + .....
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`The viscosity of the liquid phaseis critical and is desirably modified by customizing
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`This is the equivalent of producing a high viscosity continuousphase at rest. Formation of a
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`viscoelastic or a highly structured fluid phase provides additional resistive forces to particle
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