Given
the increasing number of poorly soluble and thus poorly bioavailable
active pharmaceutical materials, there is a demand for innovative
formulation platforms for such molecules. Thus a focus on enhancing
dissolution properties of poorly soluble drugs exists. Within this
study, the spin coating of acetone solutions containing 5,5-diphenyl-2,4-imidazolidinedione
(phenytoin) in various concentrations is evaluated. The results reveal
strong variations of the morphology of deposited phenytoin crystals
at silica surfaces. Individual separated particles are obtained on
low phenytoin concentrations, and closely packed particular films
form when the concentration is increased. As the material is isomorphic,
these various morphologies have the same crystalline structure. Dissolution
experiments reveal that both the apparent maximum solubility and as
the dissolution rate are strongly enhanced compared to bulk powder,
suggesting that formulation based on this preparative technique will
allow overcoming the low solubility problematic for a variety of drugs.
Abstract. This paper presents a novel one-step process for converting a liquid stabilized nano-suspension into a solid formulation via hot-melt extrusion combined with an internal devolatilization process (nanoextrusion, NANEX). A polymer (Soluplus®) was fed into the extruder and molten, after which a stable nano-suspension was added via side-feeding devices. The solvent (water) was removed by devolatilization and the polymer solidified at the outlet. The solid material can be tableted or filled in a capsule directly. The results showed that the obtained extrudates comprised nanocrystals in the de-aggregated form, confirming that a solid nano-formulation was prepared. This method is capable of overcoming many of the problems associated with other processes involving solid nano-dosage forms and poses a straightforward approach towards manufacturing such products.
The controlled preparation of different
crystal morphologies with
varying preferential orientation with respect to the substrate is
of crucial importance in many fields of applications. In this work,
the controlled preparation of different phenytoin morphologies and
the dependency of the preferential orientation of those crystallites
is related with the preparation method (solvent annealing vs drop
casting), as well as the physical–chemical interaction with
the solvents in use. While solvent annealing induces the formation
of particular structures that are partially dewetted, the drop casting
technique from various solvent results in the formation of needle-like
and elongated structures, with each having a distinct morphology.
The morphologies are explained via the Hansen solubility parameters
and correlated with the solvent vapor pressures. X-ray diffraction
experiments reveal preferential orientations with respect to the solid
substrate and indicate the surface-mediated stabilization of an unknown
polymorph of phenytoin with an elongated unit cell in the b-axis.
The preparation of solid crystalline
films at surfaces is of great
interest in a variety of fields. Within this work the preparation
of pharmaceutically relevant thin films containing the active pharmaceutical
ingredient phenytoin is demonstrated. The preparation techniques applied
include drop casting, spin coating, and vacuum deposition. For the
solution processed samples a decisive impact of the solution concentration
and the applied film fabrication technique is observed; particular
films form for all samples but with their extensions along different
crystallographic directions strongly altered. Vacuum deposition of
phenytoin reveals amorphous films, which over time crystallize into
needle-like or particular-type structures whereby a nominal thickness
of 50 nm is required to achieve a fully closed layer. Independent
of all preparation techniques, the resulting polymorph is the same
for each sample as confirmed by specular X-ray diffraction scans.
Thus, morphologies observed via optical and atomic force microscope
techniques are therefore a result of the preparation technique. This
shows that the different time scales for which crystallization is
obtained is the driving force for the various morphologies in phenytoin
thin films rather than the presence of another polymorph forming.
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