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-flightesecondary ion mass spectrometry. The co-jet milled powders demonstrated an acceptable content uniformity indicating homogeneity. In general, time-of-flight esecondary 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, cojet milling could be a viable technique to produce the combination powders for inhalation.

Advances in therapeutic nanodrug delivery systems for infectious lung diseases: a review

“…However, each of these modes has distinct advantages and limitations in the treatment of lung diseases. Oral drugs have high patient compliance and are easy to use, but the drugs must be absorbed through the gastrointestinal mucosa; thus, the mucosal penetration and stability of the drug pose challenges, particularly for poorly soluble drugs [4,5]. Many new drugs have remained undeveloped because of their low solubility [4].…”

“…In this review, we summarize recently used strategies for the treatment of infectious lung diseases based on nanodrug delivery systems, with a focus on the following carrier materials: (1) polymers, (2) liposomes, (3) solid liposomes, (4) inorganic nanoparticles, (5) nanomicelles and (6) combinational nanosystems.…”

State of the Art in Capsule-Based Dry Powder Inhalers: Deagglomeration Techniques and the Consequences for Formulation Aerosolization

“…For this purpose, special manufacturing processes such as jet-milling of the active pharmaceutical ingredient (API) are used in the pharmaceutical industry to produce micronized particles in the inhalable size range [4][5][6]. However, increasing the total particle surface area by this technology often results in very cohesive particles that have poor aerosolization efficiency and flowability [7]. To overcome this problem and produce flowable and deagglomerable powder formulations, various formulation techniques are used, such as mixing the jetmilled particles with large carrier particles (e.g., lactose) to form interactive blends [8,9].…”