The use of hydrophobic amino acids in protecting spray dried trehalose formulations against moisture-induced changes

Mah, Pei T.; O’Connell, P.; Focaroli, Stefano; Lundy, Ross; O'Mahony, Tom F.; Hastedt, Jayne E.; Gitlin, Irina; Oscarson, Stefan; Fahy, John V.; Healy, Anne Marie

doi:10.1016/j.ejpb.2019.09.014

Cited by 36 publications

(18 citation statements)

References 44 publications

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“…The amino acid most commonly used for this purpose is L-Leucine [23]. However, Mah et al recently conducted a study to compare the effects of L-Leucine and L-isoleucine in reducing moisture-induced changes in spray-dried trehalose formulations [24]. They demonstrated the greater ability of Lisoleucine to overcome elevated humidity compared to L-Leucine consisting of samples of the same concentration.…”

Section: Resultsmentioning

confidence: 99%

“…On the other hand, L-isoleucine is important for powder conservation. It has been suggested that L-isoleucine, similarly to L-Leucine, preferentially enriches the surface of the particles during the drying process [36][37][38][39] and, due to its hydrophobic nature, can act as a barrier to moisture and slow down the progress of moisture into the particles [24].…”

Section: Response Surface Analyzesmentioning

confidence: 99%

“…It appears that the decrease in activity was not caused by crystallization, but by sensitivity to temperature, as the percentage of crystalline form did not differ over time. Indeed, XRD data (Figures S8 and S9) showed that all the phage powders remained partially crystalline with diffraction peaks from crystalline L-isoleucine at 6.3 • , 12.7 • , 18.5 • , 19.1 • , 25.1 • , 25.5 • , 32.0 • and 32.4 • [24]. The presence of phages does not affect the XRD pattern because the phage content in the spray dried powder is extremely low compared to excipients [15].…”

Section: Stability Studymentioning

confidence: 99%

See 2 more Smart Citations

A Design of Experiment Approach to Optimize Spray-Dried Powders Containing Pseudomonas aeruginosaPodoviridae and Myoviridae Bacteriophages

Tabare¹,

Glonti

Cochez

et al. 2021

Viruses

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In the present study, we evaluated the effect of spray-drying formulations and operating parameters of a laboratory-scale spray-dryer on the characteristics of spray-dried powders containing two Pseudomonas aeruginosa bacteriophages exhibiting different morphotypes: a podovirus (LUZ19) and a myovirus (14-1). We optimized the production process for bacteriophage-loaded powders, with an emphasis on long-term storage under ICH (international conference on harmonization) conditions. D-trehalose-/L-isoleucine-containing bacteriophage mixtures were spray-dried from aqueous solutions using a Büchi Mini Spray-dryer B-290 (Flawil, Switzerland). A response surface methodology was used for the optimization of the spray-drying process, with the following as-evaluated parameters: Inlet temperature, spray gas flow rate, and the D-trehalose/L-isoleucine ratio. The dried powders were characterized in terms of yield, residual moisture content, and bacteriophage lytic activity. L-isoleucine has demonstrated a positive impact on the activity of LUZ19, but a negative impact on 14-1. We observed a negligible impact of the inlet temperature and a positive correlation of the spray gas flow rate with bacteriophage activity. After optimization, we were able to obtain dry powder preparations of both bacteriophages, which were stable for a minimum of one year under different ICH storage conditions (up to and including 40 °C and 75% relative humidity).

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Section: Resultsmentioning

confidence: 99%

Section: Response Surface Analyzesmentioning

confidence: 99%

Section: Stability Studymentioning

confidence: 99%

See 1 more Smart Citation

A Design of Experiment Approach to Optimize Spray-Dried Powders Containing Pseudomonas aeruginosaPodoviridae and Myoviridae Bacteriophages

Tabare¹,

Glonti

Cochez

et al. 2021

Viruses

View full text Add to dashboard Cite

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“…SD powder is mostly amorphous and tends to gain moisture leading to agglomeration. These amino acids exhibit surface-active properties and form a hydrophobic shell that protects spray-dried particles from moisture ( Matinkhoo et al., 2011 ; Mah et al., 2019 ). For example, with the addition of 20% (w/w) l-leucine to a range of formulations, there was a significant increase i.e 17.3–41.5% for FPFs ( Momin et al., 2019 ; Stewart et al., 2019 ; Lu et al., 2020 ).…”

Section: Inhaled Phage Therapy: a New Era Of Therapeuticsmentioning

confidence: 99%

Prospects of Inhaled Phage Therapy for Combatting Pulmonary Infections

Wang

Xie

Zhao

et al. 2021

Front. Cell. Infect. Microbiol.

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With respiratory infections accounting for significant morbidity and mortality, the issue of antibiotic resistance has added to the gravity of the situation. Treatment of pulmonary infections (bacterial pneumonia, cystic fibrosis-associated bacterial infections, tuberculosis) is more challenging with the involvement of multi-drug resistant bacterial strains, which act as etiological agents. Furthermore, with the dearth of new antibiotics available and old antibiotics losing efficacy, it is prudent to switch to non-antibiotic approaches to fight this battle. Phage therapy represents one such approach that has proven effective against a range of bacterial pathogens including drug resistant strains. Inhaled phage therapy encompasses the use of stable phage preparations given via aerosol delivery. This therapy can be used as an adjunct treatment option in both prophylactic and therapeutic modes. In the present review, we first highlight the role and action of phages against pulmonary pathogens, followed by delineating the different methods of delivery of inhaled phage therapy with evidence of success. The review aims to focus on recent advances and developments in improving the final success and outcome of pulmonary phage therapy. It details the use of electrospray for targeted delivery, advances in nebulization techniques, individualized controlled inhalation with software control, and liposome-encapsulated nebulized phages to take pulmonary phage delivery to the next level. The review expands knowledge on the pulmonary delivery of phages and the advances that have been made for improved outcomes in the treatment of respiratory infections.

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“…Disaccharide excipients such as trehalose are hygroscopic and can be sensitive to changes in environmental moisture which in turn can negatively affect the aerosol performance. It has been reported that leucine can improve the aerosol performance , and alleviate moisture-reduced aerosolization of spray-dried formulations. , However, leucine tends to crystallize and consequently provides a negligible stabilizing effect to proteins in spray-dried solids during storage. Thus, both protein stability and aerosol performance should be considered when designing formulations for inhalation.…”

Section: Discussionmentioning

confidence: 99%

Understanding the Impact of Protein–Excipient Interactions on Physical Stability of Spray-Dried Protein Solids

Chen

Ling²,

et al. 2021

Mol. Pharmaceutics

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Mannitol, leucine, and trehalose have been widely used in spray-dried formulations, especially for inhalation formulations. The individual contribution of these excipients on protein physical stability in spray-dried solids was studied here using bovine serum albumin (BSA) as a model protein. The spraydried solids were characterized with scanning electron microscopy, powder X-ray diffraction, and solid-state Fourier-transform infrared spectroscopy to analyze particle morphology, crystallinity, and secondary structure change, respectively. Advanced solid-state characterizations were conducted with solid-state hydrogendeuterium exchange (ssHDX) and solid-state nuclear magnetic resonance (ssNMR) to explore protein conformation and molecular interactions in the context of the system physical stability. Trehalose remained amorphous after spray-drying and was miscible with BSA, forming hydrogen bonds to maintain protein conformation, whereby this system showed the least monomer loss in the stability study. As indicated by ssNMR, both crystalline and amorphous forms of mannitol existed in the spray-dried BSA-mannitol solids, which explained its partial stabilizing effect on BSA. Leucine showed the strongest crystallization tendency after spray-drying and did not provide a stabilizing effect due to substantial immiscibility and phase separation with BSA as a result of crystal formation. This work showed novel applications of ssNMR in examining protein conformation and protein−excipient interaction in dry formulations. Overall, our results demonstrate the pivotal role of advanced solid-state characterization techniques in understanding the physical stability of spray-dried protein solids.

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The use of hydrophobic amino acids in protecting spray dried trehalose formulations against moisture-induced changes

Cited by 36 publications

References 44 publications

A Design of Experiment Approach to Optimize Spray-Dried Powders Containing Pseudomonas aeruginosaPodoviridae and Myoviridae Bacteriophages

A Design of Experiment Approach to Optimize Spray-Dried Powders Containing Pseudomonas aeruginosaPodoviridae and Myoviridae Bacteriophages

Prospects of Inhaled Phage Therapy for Combatting Pulmonary Infections

Understanding the Impact of Protein–Excipient Interactions on Physical Stability of Spray-Dried Protein Solids

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