A hot-melt extruded composition having finely divided drug-containing
particles dispersed within a polymeric and/or lipophyllic carrier matrix
is provided. The carrier softens or melts during hot-melt extrusion but
it does not dissolve the drug-containing particles during extrusion. As a
result, a majority or at least 90% wt. of the drug-containing particles
in the extrudate are deaggregated during extrusion into essentially
primary crystalline and/or amorphous particles. PEO is a suitable carrier
material for drugs insoluble in the solid state in this carrier. Various
functional excipients can be included in the carrier system to stabilize
the particle size and physical state of the drug substance in either a
crystalline and/or amorphous state. The carrier system is comprised of at
least one thermal binder, and may also contain various functional
excipients, such as: super-disintegrants, antioxidants, surfactants,
wetting agents, stabilizing agents, retardants, or similar functional
excipients. A hydrophilic polymer, such as hydroxypropyl methylcellulose
(HPMC E15), polyvinyl alcohol (PVA), or poloxamer, and/or a surfactant,
such as sodium lauryl sulfate (SLS), can be included in the composition.
A process for preparing the extrudate is conducted at a temperature
approximating or above the softening or melting temperature of the matrix
and below the point of solubilization of drug-containing particles in the
carrier system, and below the recrystallization point in the case of
amorphous fine drug particles.