Oxitropium bromide 100micrograms/dose inhaler

This study investigates the thermosalient effect in oxitropium bromide, with a focus on the role of anisotropic thermal expansion, elastic properties, and sound propagation in driving this phenomenon. Variable-temperature X-ray powder diffraction (VTXRPD) revealed significant anisotropic thermal expansion, including negative thermal expansion (NTE) along the c-axis in the low-temperature Form A. Density functional theory (DFT) calculations were used to analyze elastic properties of oxitropium bromide and confirmed that it does not exhibit negative compressibility, emphasizing thermal anisotropy as the primary factor in the phase transition. Studies of elastic constants and sound propagation demonstrated a preferred pathway for energy transfer along the z-direction, enabling rapid strain release during the phase transition. These findings confirmed that the thermosalient effect arises from cooperative molecular motion, resulting in an abrupt and energetic transformation driven by the interplay of structural anisotropy and elastic properties.

Abstract licence: CC BY

BACKROUND: Oxitropium bromide (OB) and formoterol fumarate dihydrate (FFD) are inhaler molecules that are widely used in the treatment of chronic lung diseases. OBJECTIVE: The goal of this work was to create a reversed phase-ultra performance liquid chromatography (RP-UPLC) technique for assay and identification of OB and FFD, as well as identification and estimate of its associated compounds in pressurized metered dose inhaler product (pMDI). METHOD: Separation of oxitropium and formoterol peaks were enhanced on a C18 (50 × 2.1 mm × 1.7 μm) UPLC column with ethylene-bridged-hybrid technology, The mobile phase consists of buffer (0.07 M KH2PO4) and acetonitrile (80:20, v/v). The detector wavelength of 210 nm, flow rate of pump 0.6 mL/min, and oven temperature for column were set at 25°C. The injection volume was 10 μL. The method run time was 2 min. The mobile phase was used as the solvent. RESULTS: Retention times (RTs) were 0.5 min for OB and 1.0 min for FFD. The assay analysis was linear range for all analytes within the range for concentrations 0.03-14.8 µg/mL of OB, 0.01-0.88 µg/mL of FFD. LOD values and LOQ values 0.009 and 0.026 µg/mL for OB and 0.003 and 0.009 µg/mL for FFD, respectively. Recoveries were obtained at 96.3% for OB and 97.2% for FFD. Precisions values were (as RSD, %) ≤1.5%. CONCLUSIONS: With the UPLC method developed and validated according to the current ICH guidelines, it is possible to simultaneously detect OB and FFD of assay analysis in pMDI products accurately, precisely and selectively, independent of the matrix effect. HIGHLIGHTS: The present method is the first method in the literature based on the UPLC method for this purpose. The UPLC method is a time-saving method, it provides a faster and cheaper technique than the high performance liquid chromatography (HPLC) method.

Abstract licence: CC BY