Dataset Information

Simultaneous Particle Size Reduction and Homogeneous Mixing to Produce Combinational Powder Formulations for Inhalation by the Single-Step Co-Jet Milling.

ABSTRACT: Homogeneous mixing of 2 cohesive jet-milled drug powders is a challenge for pharmaceutical manufacturing on account of their cohesive nature resulting in the formation of strong and random agglomerates. In this study, colistin and ciprofloxacin were co-jet milled to develop combinational antibiotic dry powder formulations for inhalation. The properties of particle size, morphology, content uniformity, and in vitro aerosolization were evaluated. The distribution of 2 drugs in the co-jet milled powders was assessed using time-of-flight-secondary ion mass spectrometry. The co-jet milled powders demonstrated an acceptable content uniformity indicating homogeneity. In general, time-of-flight-secondary ion mass spectrometry images showed relatively homogeneous distributions of ciprofloxacin and colistin in the co-milled formulations. Importantly, the 2 drugs generally had the similar fine particle fraction and deposition behavior in each combinational formulation supporting that the particle mixtures were relatively homogenous and could maximize the antimicrobial synergy. In conclusion, co-jet milling could be a viable technique to produce the combination powders for inhalation.

SUBMITTER: Ling J

PROVIDER: S-EPMC6708488 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Simultaneous Particle Size Reduction and Homogeneous Mixing to Produce Combinational Powder Formulations for Inhalation by the Single-Step Co-Jet Milling.

Ling Junhong J Mangal Sharad S Park Heejun H Wang Shaoning S Cavallaro Alex A Zhou Qi Tony QT

Journal of pharmaceutical sciences 20190518 9

Homogeneous mixing of 2 cohesive jet-milled drug powders is a challenge for pharmaceutical manufacturing on account of their cohesive nature resulting in the formation of strong and random agglomerates. In this study, colistin and ciprofloxacin were co-jet milled to develop combinational antibiotic dry powder formulations for inhalation. The properties of particle size, morphology, content uniformity, and in vitro aerosolization were evaluated. The distribution of 2 drugs in the co-jet milled po ...[more]

PMID: 31112716

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Project description:Treprostinil palmitil (TP), a prodrug of treprostinil, is being developed as an inhalation powder (TPIP) for the treatment of patients with pulmonary arterial hypertension (PAH) and pulmonary hypertension due to interstitial lung disease (PH-ILD). In ongoing human clinical trials, TPIP is administered via a commercially available high resistance (HR) RS01 capsule-based dry powder inhaler (DPI) device manufactured by Berry Global (formerly Plastiape), which utilizes the patient's inspiratory flow to provide the required energy to deagglomerate and disperse the powder for delivery to their lungs. In this study, we characterized the aerosol performance of TPIP in response to changes in inhalation profiles to model more realistic use scenarios, i.e., for reduced inspiratory volumes and with inhalation acceleration rates that differ from those described in the compendia. The emitted dose of TP for all combinations of inhalation profiles and volumes ranged narrowly between 79 and 89% for the 16 and 32 mg TPIP capsules at the 60 LPM inspiratory flow rate but was reduced to 72-76% for the 16 mg TPIP capsule under the scenarios at the 30 LPM peak inspiratory flow rate. There were no meaningful differences in the fine particle dose (FPD) at all conditions at 60 LPM with the 4 L inhalation volume. The FPD values for the 16 mg TPIP capsule ranged narrowly between 60 and 65% of the loaded dose for all inhalation ramp rates with a 4 L volume and at both extremes of ramp rates for inhalation volumes down to 1 L, while the FPD values for the 32 mg TPIP capsule ranged between 53 and 65% of the loaded dose for all inhalation ramp rates with a 4 L volume and at both extremes of ramp rates for inhalation volumes down to 1 L for the 60 LPM flow rate. At the 30 LPM peak flow rate, the FPD values for the 16 mg TPIP capsule ranged narrowly between 54 and 58% of the loaded dose at both extremes of the ramp rates for inhalation volumes down to 1 L. Based on these in vitro findings, the TPIP delivery system appears not to be affected by the changes in inspiratory flow profiles or inspiratory volumes that might be expected to occur in patients with PAH or PH associated with underlying lung conditions such as ILD.

Project description:A time series of experiments at high temperature have been performed to investigate the influence of particle settling on magma mixing. A natural rhyolite glass was held above a natural basalt glass in a platinum crucible. After melting of the glasses at superliquidus temperatures, a platinum sphere was placed on the upper surface of the rhyolitic melt and sank into the experimental column (rhyolitic melt above basaltic melt). Upon falling through the rhyolitic-basaltic melt interface, the Pt sphere entrained a filament of rhyolitic melt in its further fall. The quenched products of the experiments were imaged using X-ray microCT methods. The images of our time series of experiments document the formation of a rhyolite filament as it is entrained into the underlying basalt by the falling platinum sphere. When the Pt particle reached the bottom of the crucible, the entrained rhyolitic filament started to ascend buoyantly up to the initial rhyolitic-basaltic interface. This generated a significant thickness increase of a comingled "melange" layer at the interface due to "liquid rope coiling" and piling up of the filament. As a consequence, the basalt/rhyolite interface was greatly enlarged and diffusive hybridisation greatly accelerated. Further, bubbles, originating at the interface, are observed to have risen into the overlying rhyolite dragging basalt filaments with them. Upon crossing the basalt/rhyolite interface, the bubbles have non-spherical shapes as they adapt to the differing surface tensions of basaltic and rhyolitic melts. Major element profiles, measured across the rhyolite filaments, exhibit asymmetrical shapes from the rhyolite into the basalt. Na and Ti reveal uphill diffusion from the rhyolite towards the interface in the filament cross sections. These results reveal the potential qualitative complexity of the mingling process between rhyolitic and basaltic magmas in the presence of sinking crystals. They imply that crystal-rich magma mingling may be expected to be accelerated with respect to crystal-poor systems. We urge the further fluid dynamic analysis of these phenomena, obtainable for the first time using detailed tomographic imaging.

Dataset Information

Simultaneous Particle Size Reduction and Homogeneous Mixing to Produce Combinational Powder Formulations for Inhalation by the Single-Step Co-Jet Milling.

Publications

Simultaneous Particle Size Reduction and Homogeneous Mixing to Produce Combinational Powder Formulations for Inhalation by the Single-Step Co-Jet Milling.

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