MilliporeSigma
  • Home
  • Search Results
  • The influence of secondary processing on the structural relaxation dynamics of fluticasone propionate.

The influence of secondary processing on the structural relaxation dynamics of fluticasone propionate.

AAPS PharmSciTech (2014-11-16)
Roberto Depasquale, Sau L Lee, Bhawana Saluja, Jagdeep Shur, Robert Price
ABSTRACT

This study investigated the structural relaxation of micronized fluticasone propionate (FP) under different lagering conditions and its influence on aerodynamic particle size distribution (APSD) of binary and tertiary carrier-based dry powder inhaler (DPI) formulations. Micronized FP was lagered under low humidity (LH 25 C, 33% RH [relative humidity]), high humidity (HH 25°C, 75% RH) for 30, 60, and 90 days, respectively, and high temperature (HT 60°C, 44% RH) for 14 days. Physicochemical, surface interfacial properties via cohesive-adhesive balance (CAB) measurements and amorphous disorder levels of the FP samples were characterized. Particle size, surface area, and rugosity suggested minimal morphological changes of the lagered FP samples, with the exception of the 90-day HH (HH90) sample. HH90 FP samples appeared to undergo surface reconstruction with a reduction in surface rugosity. LH and HH lagering reduced the levels of amorphous content over 90-day exposure, which influenced the CAB measurements with lactose monohydrate and salmeterol xinafoate (SX). CAB analysis suggested that LH and HH lagering led to different interfacial interactions with lactose monohydrate but an increasing adhesive affinity with SX. HT lagering led to no detectable levels of the amorphous disorder, resulting in an increase in the adhesive interaction with lactose monohydrate. APSD analysis suggested that the fine particle mass of FP and SX was affected by the lagering of the FP. In conclusion, environmental conditions during the lagering of FP may have a profound effect on physicochemical and interfacial properties as well as product performance of binary and tertiary carrier-based DPI formulations.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Poly(tetrafluoroethylene), beads
Sigma-Aldrich
Poly(tetrafluoroethylene), powder, 35 μm particle size
Sigma-Aldrich
Poly(tetrafluoroethylene), powder (free-flowing), ≤12 μm particle size
Sigma-Aldrich
Poly(tetrafluoroethylene), powder (free-flowing), 1 μm particle size
Sigma-Aldrich
Acetonitrile, electronic grade, 99.999% trace metals basis
Sigma-Aldrich
Acetonitrile
Sigma-Aldrich
Acetonitrile, ≥99.5%, ACS reagent
Sigma-Aldrich
Acetonitrile, anhydrous, 99.8%
Sigma-Aldrich
Acetonitrile, HPLC Plus, ≥99.9%, poly-coated bottles
Sigma-Aldrich
Methanol-12C, 99.95 atom % 12C
Supelco
Acetonitrile, HPLC grade, ≥99.93%
Sigma-Aldrich
Poly(tetrafluoroethylene), powder, 200 μm particle size
Supelco
Methanol solution, NMR reference standard, 4% in methanol-d4 (99.8 atom % D), NMR tube size 5 mm × 8 in.
Sigma-Aldrich
Methanol solution, NMR reference standard, 4% in methanol-d4 (99.8 atom % D), NMR tube size 3 mm × 8 in.
Sigma-Aldrich
Poly(tetrafluoroethylene), powder, ≥350 μm particle size
Supelco
Methanol solution, contains 0.10 % (v/v) formic acid, UHPLC, suitable for mass spectrometry (MS), ≥99.5%
Sigma-Aldrich
Poly(tetrafluoroethylene), powder, >40 μm particle size
Sigma-Aldrich
Acetonitrile solution, contains 0.05 % (w/v) ammonium formate, 0.1 % (v/v) formic acid, 5 % (v/v) water, suitable for HPLC
Sigma-Aldrich
Acetonitrile solution, contains 0.1 % (v/v) trifluoroacetic acid, suitable for HPLC
Sigma-Aldrich
Acetonitrile solution, contains 10.0% acetone, 40.0% 2-propanol, 0.05% formic acid
Sigma-Aldrich
Methanol, anhydrous, 99.8%
Sigma-Aldrich
Methanol, suitable for HPLC, gradient grade, 99.93%
Sigma-Aldrich
Acetone, ≥99%, meets FCC analytical specifications
Sigma-Aldrich
Acetone, natural, ≥97%
Sigma-Aldrich
Acetonitrile solution, contains 0.05 % (v/v) trifluoroacetic acid
Sigma-Aldrich
Acetone, suitable for HPLC, ≥99.9%
Sigma-Aldrich
Cyclohexane, anhydrous, 99.5%
Sigma-Aldrich
D-Lactose monohydrate, ACS reagent
Sigma-Aldrich
D-Lactose monohydrate, BioUltra, ≥99.5% (HPLC)
Sigma-Aldrich
D.E.R. 332, used as embedding medium