The influence of amino acids on aztreonam spray-dried powders for inhalation

Yang, Xiaofei; Xu, Ying; Qu, Da-Sheng; Li, Haoying

doi:10.1016/j.ajps.2015.08.002

Cited by 31 publications

(15 citation statements)

References 28 publications

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“…These results have been correlated to the morphology and shape of produced particles (Section 3). Regarding the inhalation of Aztreonam for the treatment of local pulmonary infection, Yang et al have recently compared the effects of three slightly water soluble amino acids (i.e., hydrophilic glycine, histidine containing an imidazol group and L-leucine) on particle characteristics when used in Aztreonam-combining formulations [53]. The spray drying of Aztreonam and amino acids (40/60) produced different powder particles in terms of density, morphology, and size.…”

Section: Amino Acidsmentioning

confidence: 99%

Influence of Composition and Spray-Drying Process Parameters on Carrier-Free DPI Properties and Behaviors in the Lung: A review

Lechanteur

Évrard

2020

Pharmaceutics

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Although dry powder inhalers (DPIs) have attracted great interest compared to nebulizers and metered-dose inhalers (MDIs), drug deposition in the deep lung is still insufficient to enhance therapeutic activity. Indeed, it is estimated that only 10–15% of the drug reaches the deep lung while 20% of the drug is lost in the oropharyngeal sphere and 65% is not released from the carrier. The potentiality of the powders to disperse in the air during the patient’s inhalation, the aerosolization, should be optimized. To do so, new strategies, in addition to classical lactose-carrier, have emerged. The lung deposition of carrier-free particles, mainly produced by spray drying, is higher due to non-interparticulate forces between the carrier and drug, as well as better powder uniformity and aerosolization. Moreover, the association of two or three active ingredients within the same powder seems easier. This review is focused on a new type of carrier-free particles which are characterized by a sugar-based core encompassed by a corrugated shell layer produced by spray drying. All excipients used to produce such particles are dissected and their physico-chemical properties (Péclet number, glass transition temperature) are put in relation with the lung deposition ability of powders. The importance of spray-drying parameters on powders’ properties and behaviors is also evaluated. Special attention is given to the relation between the morphology (characterized by a corrugated surface) and lung deposition performance. The understanding of the closed relation between particle material composition and spray-drying process parameters, impacting the final powder properties, could help in the development of promising DPI systems suitable for local or systemic drug delivery.

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Section: Amino Acidsmentioning

confidence: 99%

Influence of Composition and Spray-Drying Process Parameters on Carrier-Free DPI Properties and Behaviors in the Lung: A review

Lechanteur

Évrard

2020

Pharmaceutics

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“…In the case of carrier-free DPI systems, the application of large carriers can be avoided with the use of special excipients and technologies (e.g. co-spray drying) (Chvatal et al, 2017;Yang et al, 2015). These systems yield around 50-60 % FPF results due to the apparent high cohesive properties between the active ingredient's particles (Kadota et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Novel dry powder inhaler formulation containing antibiotic using combined technology to improve aerodynamic properties

Ambrus

Benke

Farkas

et al. 2018

European Journal of Pharmaceutical Sciences

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Dry Powder Inhaler (DPI) could offer a propellant-free, easy-to-use powder form ensuring better stability than liquid dosage forms. Therefore the development of traditional carrier-based and carrier-free new generation systems is a determinative factor in the field of DPI formulation. The purpose of our research work was to combine these two systems, utilizing their beneficial properties to produce a novel pulmonary drug delivery system containing ciprofloxacin hydrochloride (CIP). Co-spray drying, surface smoothing and the preparation of an interactive physical mixture were applied as the technological procedures of sample preparation. The carrier-based and carrier-free formulations, as well as the developed novel product were compared to each other. Structural investigations were made by X-ray powder diffraction and micrometric properties (habit, bulk density) were determined. Particle interactions were also evaluated to investigate surface free energy, cohesive-adhesive forces, and spreading coefficient. In vitro aerodynamic properties (mass median aerodynamic diameter), fine particle fraction (FPF) and emitted dose of DPIs were measured using Andersen Cascade Impactor. A novel in silico Stochastic Lung Model was also used to quantify the amount of particles deposited at the target area. The novel-formulated composition presented amorphous spherical particles with an average size of about 2 μm. The in vitro aerodynamic investigations showed a variance in FPF as a function of formulation method (carrier-based: 24%, carrier-free: 54% and applying the novel combination method: 63%). The in silico deposition results were in line with the in vitro measurements and yielded increased lung doses for the sample prepared by the combined technology. This novel DPI formulation provides an opportunity for a more effective therapy with deeper deposition of CIP.

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“…The moisture content is usually measured by thermogravimetric analysis (TGA) or Karl Fischer (KF) colorimetric titration. The moisture content is influenced by the properties of the excipient(s), e.g., powders prepared with mannitol have a relative low moisture content [ 183 ], dextran-based powders have a relative high moisture content [ 184 ], and amino acids as excipients can diminish the moisture content in the spray-dried powders [ 185 ]. The use of high inlet temperatures and feedstock concentrations, and nonaqueous solvents, lead to lower moisture contents, whereas high aspirator and feedstock rates have the opposite effect [ 186 ].…”

Section: Critical Quality Attributes Of Inhalable Dry Powdersmentioning

confidence: 99%

Inhaled RNA Therapeutics for Obstructive Airway Diseases: Recent Advances and Future Prospects

Thakur

Zhang

et al. 2021

Pharmaceutics

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Obstructive airway diseases, e.g., chronic obstructive pulmonary disease (COPD) and asthma, represent leading causes of morbidity and mortality worldwide. However, the efficacy of currently available inhaled therapeutics is not sufficient for arresting disease progression and decreasing mortality, hence providing an urgent need for development of novel therapeutics. Local delivery to the airways via inhalation is promising for novel drugs, because it allows for delivery directly to the target site of action and minimizes systemic drug exposure. In addition, novel drug modalities like RNA therapeutics provide entirely new opportunities for highly specific treatment of airway diseases. Here, we review state of the art of conventional inhaled drugs used for the treatment of COPD and asthma with focus on quality attributes of inhaled medicines, and we outline the therapeutic potential and safety of novel drugs. Subsequently, we present recent advances in manufacturing of thermostable solid dosage forms for pulmonary administration, important quality attributes of inhalable dry powder formulations, and obstacles for the translation of inhalable solid dosage forms to the clinic. Delivery challenges for inhaled RNA therapeutics and delivery technologies used to overcome them are also discussed. Finally, we present future prospects of novel inhaled RNA-based therapeutics for treatment of obstructive airways diseases, and highlight major knowledge gaps, which require further investigation to advance RNA-based medicine towards the bedside.

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The influence of amino acids on aztreonam spray-dried powders for inhalation

Cited by 31 publications

References 28 publications

Influence of Composition and Spray-Drying Process Parameters on Carrier-Free DPI Properties and Behaviors in the Lung: A review

Influence of Composition and Spray-Drying Process Parameters on Carrier-Free DPI Properties and Behaviors in the Lung: A review

Novel dry powder inhaler formulation containing antibiotic using combined technology to improve aerodynamic properties

Inhaled RNA Therapeutics for Obstructive Airway Diseases: Recent Advances and Future Prospects

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