1 research outputs found
Millisecond Self-Assembly of Stable Nanodispersed Drug Formulations
We report the development of a new
spray-drying and nanoparticle assembly process (SNAP) that enables
the formation of stable, yet rapidly dissolving, sub-200 nm nanocrystalline
particles within a high <i>T</i><sub>g</sub> glassy matrix.
SNAP expands the class of drugs that spray-dried dispersion (SDD)
processing can address to encompass highly crystalline, but modestly
hydrophobic, drugs that are difficult to process by conventional SDD.
The process integrates rapid precipitation and spray-drying within
a custom designed nozzle to produce high supersaturations and precipitation
of the drug and high <i>T</i><sub>g</sub> glassy polymer.
Keeping the time between precipitation and drying to tens of milliseconds
allows for kinetic trapping of drug nanocrystals in the polymer matrix.
Powder X-ray diffraction, solid state 2D NMR, and SEM imaging shows
that adding an amphiphilic block copolymer (BCP) to the solvent gives
essentially complete crystallization of the active pharmaceutical
ingredient (API) with sub-200 nm domains. In contrast, the absence
of the block copolymer results in the API being partially dispersed
in the matrix as an amorphous phase, which can be sensitive to changes
in bioavailability over time. Quantification of the API–excipient
interactions by 2D <sup>13</sup>C–<sup>1</sup>H NMR correlation
spectroscopy shows that the mechanism of enhanced nanocrystal formation
is not due to interactions between the drug and the BCP, but rather
the BCP masks interactions between the drug and hydrophobic regions
of the matrix polymers. BCP-facilitated SNAP samples show improved
stability during aging studies and rapid dissolution and release of
API <i>in vitro</i>