Effects of Moisture-Induced Crystallization on the Aerosol Performance of Spray Dried Amorphous Ciprofloxacin Powder Formulations

Shetty, Nivedita; Zeng, Leilei; Mangal, Sharad; Nie, Haichen; Rowles, Matthew R.; Guo, Rui; Han, Youngwoo; Park, Joon Hyeong; Zhou, Qi Tony

doi:10.1007/s11095-017-2281-5

Cited by 42 publications

(37 citation statements)

References 41 publications

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“…However, they have around 50-60% FPF results due to the apparent high cohesive properties between the active ingredient's particles [26,27]. Many publications deal with the development of DPI containing ciprofloxacin or ciprofloxacin hydrochloride [12,[28][29][30][31][32][33]. A serious challenge of our previous work was using the benefits of these two formulations (applying 1:10 ratio and current inhaled antibiotics are $100 mg), the novel combined formulation (a co-spray-dried drug blended with surface modified lactose) produced by us resulted in a higher FPF value than the carrier-based and carrier-free DPI formulations [18].…”

Section: Introductionmentioning

confidence: 99%

Stability test of novel combined formulated dry powder inhalation system containing antibiotic: physical characterization andin vitro–in silicolung deposition results

Benke

Farkas

Balásházy

et al. 2019

Drug Development and Industrial Pharmacy

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Objective: The aim was to study the stability of dry powder inhaler (DPI) formulations containing antibiotic with different preparation wayscarrier-based, carrier-free, and novel combined formulationand thereby to compare their physicochemical and in vitro-in silico aerodynamical properties before and after storage. Presenting a novel combined technology in the field of DPI formulation including the carrierbased and carrier-free methods, it is the most important reason to introduce this stable formulation for the further development of DPIs. Methods: The structure, the residual solvent content, the interparticle interactions, the particle size distribution and the morphology of the samples were studied. The aerodynamic values were determined based on the cascade impactor in vitro lung model. We tested the in silico behavior of the novel combined formulated samples before and during storage. Results: The physical measurements showed that the novel combined formulated sample was the most favorable. It was found that thanks to the formulation technique and the use of magnesium stearate (MgSt) has a beneficial effect on the stability compared with the carrier-based formulation without MgSt and carrier-free formulations. The results of in vitro and in silico lung models were consistent with the physical results, so the highest deposition was found for the novel combined formulated sample during the storage. Conclusions: It can be established that after the storage a novel combined formulated DPI contained amorphous drug to have around 2.5 lm mass median aerodynamic diameter and nearly 50% fine particle fraction predicted high lung deposition in silico also.

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Section: Introductionmentioning

confidence: 99%

Stability test of novel combined formulated dry powder inhalation system containing antibiotic: physical characterization andin vitro–in silicolung deposition results

Benke

Farkas

Balásházy

et al. 2019

Drug Development and Industrial Pharmacy

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“…The resultant capsules were used in a low-resistance RS01 DPI device (similar design to Osmohaler, Plastiape S.p.A., Osnago, Italy), with 4 L of air passing through the inhaler at an airflow of 100 L/min for 2.4 s, with a pressure drop of approximately 4 kPa (39). Drugs retained in the capsule, inhaler device, USP throat and Stage 1–8 of the impactor were collected using 20 mL of a co-solvent consisting of 1:1 v/v of 20 mM potassium dihydrogen phosphate (adjusted to pH 5 with 10 % w/v sodium hydroxide) and methanol.…”

Section: Methodsmentioning

confidence: 99%

Understanding the Impacts of Surface Compositions on the In-Vitro Dissolution and Aerosolization of Co-Spray-Dried Composite Powder Formulations for Inhalation

Mangal

Park

et al. 2018

Pharm Res

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Purpose: Dissolution behavior of dry powder inhaler (DPI) antibiotic formulations in the airways may affect their efficacy especially for poorly-soluble antibiotics such as azithromycin. The main objective of this study was to understand the effects of surface composition on the dissolution of spray dried azithromycin powders by itself and in combination with colistin. Methods: Composite formulations of azithromycin (a poorly water-soluble molecule) and colistin (a water-soluble molecule) were produced by spray drying. The resultant formulations were characterized for particle size, morphology, surface composition, solid-state properties, solubility and dissolution. Results: The results demonstrate that surfaces composition has critical impacts on the dissolution of composite formulations. Colistin was shown to increase the solubility of azithromycin. For composite formulations with no surface colistin, azithromycin released at a similar dissolution rate as the spray-dried azithromycin alone. An increase in surface colistin concentration was shown to accelerate the dissolution of azithromycin. The dissolution of colistin from the composite formulations was significantly slower than the spray-dried pure colistin. In addition, FTIR spectrum showed intermolecular interactions between azithromycin and colistin in the composite formulations, which could contribute to the enhanced solubility and dissolution of azithromycin. Conclusions: Our study provides fundamental understanding of the effects of surface concentration of colistin on azithromycin dissolution of co-spray-dried composite powder formulations.

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“…Previous studies have shown that the spray-dried ciprofloxacin is amorphous, which tends to crystallize upon storage and affects the aerosolization. 12 Because the jet-milled ciprofloxacin was crystalline, it is likely to have better physical stability than the spray-dried amorphous ciprofloxacin particles.…”

Section: Powder X-ray Diffractionmentioning

confidence: 99%

“…The unstable amorphous particles may convert into more thermodynamically stable crystalline form, 11 which could alter the aerosolization behavior. [12][13][14] Although the jet-milled particles are in general very cohesive with poor flowability and unsatisfactory aerosolization behavior, 15,16 jet milling is still the mainstay approach to manufacture inhalable drug particles in the industrial practice. 7 Studies have also shown that co-jet milling with lubricants may potentially facilitate simultaneous particle size reduction and particle surface coating, which resulted in improved aerosolization performance.…”

Section: Introductionmentioning

confidence: 99%

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

Ling

Mangal

Park

et al. 2019

Journal of Pharmaceutical Sciences

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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.

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Effects of Moisture-Induced Crystallization on the Aerosol Performance of Spray Dried Amorphous Ciprofloxacin Powder Formulations

Abstract: This study provides a fundamental understanding in moisture-induced physical and aerosol instability of the spray dried powder formulations.

Cited by 42 publications

References 41 publications

Stability test of novel combined formulated dry powder inhalation system containing antibiotic: physical characterization andin vitro–in silicolung deposition results

Stability test of novel combined formulated dry powder inhalation system containing antibiotic: physical characterization andin vitro–in silicolung deposition results

Understanding the Impacts of Surface Compositions on the In-Vitro Dissolution and Aerosolization of Co-Spray-Dried Composite Powder Formulations for Inhalation

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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