Protection of hydrophobic amino acids against moisture-induced deterioration in the aerosolization performance of highly hygroscopic spray-dried powders

Yu, Jiaqi; Chan, Hak‐Kim; Gengenbach, Thomas R.; Denman, John A.

doi:10.1016/j.ejpb.2017.06.023

Cited by 42 publications

(25 citation statements)

References 16 publications

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“…The aerodynamic diameter ( d ae ), which was applied to characterize the aerodynamic properties of particles [32,33], represented the inherent tendency of aerosol deposition in both gravitational settling and inertial impaction [34]. Aerosolization performance was influenced by multiple powder properties such as particle size [33], density [15], shape [35], and surface roughness [20], etc. Besides, d ae is affected by several factors including density and shape.…”

Section: Resultsmentioning

confidence: 99%

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Moisture-Resistant Co-Spray-Dried Netilmicin with l-Leucine as Dry Powder Inhalation for the Treatment of Respiratory Infections

et al. 2018

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Netilmicin (NTM) is one of the first-line drugs for lower respiratory tract infections (LRTI) therapy, but its nephrotoxicity and ototoxicity caused by intravenous injection restrict its clinical application. Dry powder inhalation (DPI) is a popular local drug delivery system that is introduced as a solution. Due to the nature of NTM hygroscopicity that hinders its direct use through DPI, in this study, L-leucine (LL) was added into NTM dry powder to reduce its moisture absorption rate and improve its aerosolization performance. NTM DPIs were prepared using spray-drying with different LL proportions. The particle size, density, morphology, crystallinity, water content, hygroscopicity, antibacterial activity, in vitro aerosolization performance, and stability of each formulation were characterized. NTM DPIs were suitable for inhalation and amorphous with a corrugated surface. The analysis indicated that the water content and hygroscopicity were decreased with the addition of LL, whilst the antibacterial activity of NTM was maintained. The optimal formulation ND2 (NTM:LL = 30:1) showed high fine particle fraction values (85.14 ± 8.97%), which was 2.78-fold those of ND0 (100% NTM). It was stable after storage at 40 ± 2 °C, 75 ± 5% relative humidity (RH). The additional LL in NTM DPI successfully reduced the hygroscopicity and improved the aerosolization performance. NTM DPIs were proved to be a feasible and desirable approach for the treatment of LRTI.

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Section: Resultsmentioning

confidence: 99%

“…First, the carrier and drug are physically mixed to improve the flowability and dispersibility [15,16,17]. Second, the carrier and drug are dissolved and co-spray-dried [18,19,20]. However, the added carrier amount is generally large.…”

Section: Introductionmentioning

confidence: 99%

Moisture-Resistant Co-Spray-Dried Netilmicin with l-Leucine as Dry Powder Inhalation for the Treatment of Respiratory Infections

et al. 2018

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“…It has been reported that the higher FPF translates into lower and upper airway doses and higher deposited doses in the lungs. 47,48 These results indicated that the small particles generated by Pari Boy SX (red) deposition within the respiratory system is dominated by sedimentation and diffusion within the deep lung. Furthermore, the values of D 50 and MMAD of Pari LC Plus and Pari blue were larger than other three nebulizers with lower FPF values, indicating that the aerosol particles of RIS emitted by these two nebulizers may mainly deposit by impaction in the oropharynx and bronchi, prior to reaching the lungs.…”

Section: Discussionmentioning

confidence: 88%

Characterization and comparison of Re-Du-Ning aerosol particles generated by different jet nebulizers

Zhang

Cheng

et al. 2019

RSC Adv.

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“…38 Water vapor absorption by a more polar amorphous solid, such as sucrose, on the other hand, can reach values of about 6% w/w at 32% RH where rapid crystallization occurs, 39 while as much as 10% w/w water is absorbed by amorphous lactose at about 40% RH, followed by rapid crystallization to the monohydrate. 40 To our knowledge, there have been essentially no systematic studies reported on the absorption of water by amorphous small molecule coformers or coamorphous systems, 41 but in many cases, we might expect similar behavior as with sucrose and lactose. Some studies with crystalline polar materials might provide some insights.…”

Section: Effects Of Exposure Of Amorphous Coformers and Amorphous Apimentioning

confidence: 97%

Coamorphous Active Pharmaceutical Ingredient–Small Molecule Mixtures: Considerations in the Choice of Coformers for Enhancing Dissolution and Oral Bioavailability

Newman¹,

Reutzel‐Edens

Zografi

2018

Journal of Pharmaceutical Sciences

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In the recent years, coamorphous systems, containing an active pharmaceutical ingredient (API) and a small molecule coformer have appeared as alternatives to the use of either amorphous solid dispersions containing polymer or cocrystals of API and small molecule coformers, to improve the dissolution and oral bioavailability of poorly soluble crystalline API. This Commentary article considers the relative properties of amorphous solid dispersions and coamorphous systems in terms of methods of preparation; miscibility; glass transition temperature; physical stability; hygroscopicity; and aqueous dissolution. It also considers important questions concerning the fundamental criteria to be used for the proper selection of a small molecule coformer regarding its ability to form either coamorphous or cocrystal systems. Finally, we consider various aspects of product development that are specifically associated with the formulation of commercial coamorphous systems as solid oral dosage forms. These include coformer selection; screening; methods of preparation; preformulation; physical stability; bioavailability; and final formulation. Through such an analysis of coamorphous API-small molecule coformer systems, against the more widely studied API-polymer dispersions and cocrystals, it is believed that the strengths and weaknesses of coamorphous systems can be better understood, leading to more efficient formulation and manufacture of such systems for enhancing oral bioavailability.

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Protection of hydrophobic amino acids against moisture-induced deterioration in the aerosolization performance of highly hygroscopic spray-dried powders

Cited by 42 publications

References 16 publications

Moisture-Resistant Co-Spray-Dried Netilmicin with l-Leucine as Dry Powder Inhalation for the Treatment of Respiratory Infections

Moisture-Resistant Co-Spray-Dried Netilmicin with l-Leucine as Dry Powder Inhalation for the Treatment of Respiratory Infections

Characterization and comparison of Re-Du-Ning aerosol particles generated by different jet nebulizers

Coamorphous Active Pharmaceutical Ingredient–Small Molecule Mixtures: Considerations in the Choice of Coformers for Enhancing Dissolution and Oral Bioavailability

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