82. Sathigari,
Sateesh Kumar; Ober,
Courtney A.; Sanganwar, Ganesh P.; Gupta, Ram B.; Babu, R. Jayachandra, Single-step
preparation and deagglomeration of itraconazole microflakes by
supercritical antisolvent method for dissolution
enhancement, Journal of Pharmaceutical Sciences (2011), 100(7), 2952-2965.
Abstract
Itraconazole (ITZ) microflakes
were produced by supercritical antisolvent (SAS)
method and simultaneously mixed with pharmaceutical excipients in a single step
to prevent drug agglomeration. Simultaneous ITZ particle formation and mixing
with fast-flo lactose (FFL) was performed in a
high-pressure stirred vessel at 116 bar and 40°C by
the SAS–drug excipient mixing (SAS–DEM) method. The effects of stabilizers,
such as sodium dodecyl sulfate and poloxamer 407
(PLX), on particle formation and drug dissolution were studied. Drug–excipient
formulations were characterized for surface morphology, crystallinity,
drug–excipient interactions, drug content uniformity, and drug dissolution
rate. Mixture of drug microflakes and FFL formed by
the SAS–DEM process shows that the process was successful in overcoming
drug–drug agglomeration. PLX produced crystalline drug flakes in loose
agglomerates with superior dissolution and flow properties even at higher drug
loadings. Characterization studies confirmed the crystallinity
of the drug and absence of chemical interactions during the SAS process. The
dissolution of ITZ was substantially higher due to SAS and SAS–DEM processes;
this improvement can be attributed to the microflake
particle structures, effective deagglomeration, and
wetting of the drug flakes with the excipients. © 2011 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm
Sci 100:2952–2965, 2011
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