The effect of ethanol on the habit and in vitro aerodynamic results of dry powder inhalation formulations containing ciprofloxacin hydrochloride

Abstract

Graphical abstract Dry powder inhalation (DPI) formulations containing ciprofloxacin hydrochloride (CIP) as a model drug were prepared by spray-drying in the presence of different ethanol concentrations. The role of ethanol on the habit and aerodynamics of the DPI samples was examined in detail. The roughness, depth and width of the dimples were uniquely expressed. A new correlation was determined between the mass median aerodynamic diameter (MMAD)/D (0.5) ratio and cohesion work (Wc). DPI formulation containing 30% ethanol in the stock solution had the best in vitro aerodynamic results.

Development of novel formulated ciprofloxacin hydrochloride containing dry powder inhalation system

“…This can be best understood from schematic figures, since the particles may contact over a larger surface area because of their dimpled nature and nearly similar surface morphology (inc. roughness, depth, and width of the dimples) (Table 13.). This context has been previously referred to in Lechanteur et al [129] publication [53]. Nevertheless, for CIPspdEtOH 20 and CIPspdEtOH 30 samples, a notable decrease in Wc is observed, which can be explained as morphological differences of individual particles shown in the SEM records, as also indicated by the larger variation in the AFM-detected dimples.…”

“…The resulting composites alone gave good lung deposition results thus, the use of large carrier particles can be eliminated [47]. The most common bottom-up DPI production technology is spd, which based on its advantages and disadvantages, proves to be the most favorable method of production [53]. Formulations prepared by this technology are categorized in the literature according to their habit, with some overlap.…”

“…However, the literature generally describes the occurrence of dimples as a positive factor for aerodynamic results [78], but they provide higher connectivity for particles with similar morphology. Hence, it is assumed that the larger (wide and deep) dimples, the somewhat variable morphology of particles, and thus the more beneficial Wc values imply comparatively improved in vitro aerodynamic results for CIPspdEtOH 20 and CIPspdEtOH 30 formulations [53]. The different morphologies and D [0.5] values of the samples are due to the different evaporation rates of water and EtOH.…”

“…At higher EtOH concentrations, the higher internal pressure may cause the particles to swell and crack more [130]. Thus, mixtures of these solvents in different proportions in the stock solution will lead to different morphologies during the spd process under the same conditions [53]. The EF value must be between 85% and 115% for in vitro APSD tests [132].…”

Development of meloxicam potassium-containing co-spray-dried inhalation powder with sodium stearate

“…Although it has been shown from literature descriptions that dimples are more aerodynamically advantageous than particles with a smooth surface (44). Nevertheless, our previous publication (43) has highlighted that particles with nearly identical morphologies, especially those containing dimples, can be highly agglomerated, thereby making their aerosolization and dispersion more difficult.…”