91. Ober,
Courtney A.; Kalombo, Lonji;
Swai, Hulda; Gupta, Ram B.,
Preparation of rifampicin/lactose microparticle
composites by a supercritical antisolvent-drug
excipient mixing technique for inhalation delivery, Powder Technology 2013,
236, 132-138.
Abstract
Rifampicin
(RIF) is precipitated in the presence of inhalable lactose particles using a
supercritical antisolvent-drug excipient mixing
(SAS-DEM) technique to create RIF/lactose microparticle
composites intended to improve the effectiveness of pulmonary tuberculosis
treatments by increasing the respirable fraction of
RIF. These RIF/lactose microparticle composites are
prepared by dissolving RIF in a liquid solvent and spraying the solution into a
high pressure vessel containing supercritical CO2 and suspended lactose
particles. As the CO2 extracts the liquid solvent, RIF
microparticles precipitate to form a microparticle composite mixture with the lactose particles.
The effects of solvent, RIF concentration, and RIF to
lactose loading are examined. The RIF/lactose microparticle
composites are characterized for composition, particle size and surface
morphology, crystallinity, thermal behavior, and
physicochemical properties. By placing 1000 mg of lactose microfine
in the vessel and varying the spraying time of 1 mg/mL and 5 mg/mL RIF in
methanol solutions, RIF/lactose microparticle
composites of 1.2%, 7.2%, 14.0%, and 25.7% RIF with relative standard
deviations of 5.7%, 4.5%, 5.2%, and 2.3%, respectively, are prepared. Based on scanning electron microscopy, homogeneous RIF/lactose
composites consisting of spherical particles less than 8 μm
in diameter are produced. X-ray diffraction reveals that the SAS
precipitation of RIF form I from methanol produces a polymorphic mixture of RIF
form I and RIF dihydrate, due to trace water content
in the solvent, while both RIF and lactose retain their individual crystalline
structures during SAS-DEM processing. Based on differential scanning calorimetry RIF dihydrate converts to amorphous RIF upon heating. Fourier
transform infrared spectroscopy demonstrates the absence of chemical
interactions between the RIF and lactose proving a physical composite of the
two is produced by the SAS-DEM process, and indicating that the therapeutic
effectiveness of the drug should be unaffected.
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