Effect of formulation and inhaler parameters on the dispersion of spray freeze dried voriconazole particles

Liao, Qiuying; Lam, Ivan C.H.; Lin, Hinson H.S.; Wan, Leon T.L.; Lo, Jason C.K.; Tai, Waiting; Kwok, Philip Chi Lip; Lam, Jenny K.W.

doi:10.1016/j.ijpharm.2020.119444

Cited by 29 publications

(22 citation statements)

References 30 publications

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“…The volumetric size distribution of the spray-freeze-dried powders was evaluated by laser diffraction. A laser diffractometer configured with a dosing unit for inhalers and nebulizers (HELOS/KR+INHALER, Sympatec GmbH, Clausthal-Zellerfeld, Germany) was used to determine the size distribution of the particles dispersed from a Breezhaler ® (Novartis AG, Basel, Switzerland) as previously described [ 20 ]. In brief, the Breezhaler ® was mounted onto the central unit of the INHALER module by inserting the mouthpiece into the adaptor horizontally.…”

Section: Methodsmentioning

confidence: 99%

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Inhalable Protein Powder Prepared by Spray-Freeze-Drying Using Hydroxypropyl-β-Cyclodextrin as Excipient

Pan

Lam

2021

Pharmaceutics

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The prospect of inhaled biologics has garnered particular interest given the benefits of the pulmonary route of administration. Pertinent considerations in producing inhalable dry powders containing biological medicines relate to aerosol performance and protein stability. Spray-freeze-drying (SFD) has emerged as an established method to generate microparticles that can potentially be deposited in the lungs. Here, the SFD conditions and formulation composition were evaluated using bovine serum albumin (BSA) as a model protein and 2-hydroxypropyl-beta-cyclodextrin (HPβCD) as the protein stabilizer. A factorial design analysis was performed to investigate the effects of BSA content, solute concentration of feed solution, and atomization gas flow rate on dispersibility (as an emitted fraction), respirability (as fine particle fraction), particle size, and level of protein aggregation. The atomization gas flow rate was identified as a significant factor in influencing the aerosol performance of the powder formulations and protein aggregation. Nonetheless, high atomization gas flow rate induced aggregation, highlighting the need to further optimize the formulation. Of note, all the formulations exhibited excellent dispersibility, while no fragmentation of BSA occurred, indicating the feasibility of SFD and the promise of HPβCD as an excipient.

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Section: Methodsmentioning

confidence: 99%

“…The aerosol performance of the spray-freeze-dried powders was evaluated with an NGI (Copley Scientific, Nottingham, UK) as previously described [ 20 ]. For each dispersion of the factorial design formulations, 3.5 ± 0.1 mg of powder was encapsulated in a size 3 gelatin capsule.…”

Section: Methodsmentioning

confidence: 99%

Inhalable Protein Powder Prepared by Spray-Freeze-Drying Using Hydroxypropyl-β-Cyclodextrin as Excipient

Pan

Lam

2021

Pharmaceutics

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“…The volumetric size distribution of the spray-dried powders was measured by laser diffraction (HELOS/KR incorporated with an inhaler module, Sympatec, Clausthal-Zellerfeld, Germany) as previously reported [20]. Approximately 5 mg of powder was loaded in gelatin capsules and dispersed from a Breezhaler ® at a flow rate of 60 L/min and a pressure drop of 1.5 kPa.…”

Section: Particle Size Distributionmentioning

confidence: 99%

“…For each formulation, a Size 3 gelatin capsule (Capsugel, Lonza, NSW, Australia) containing around 7 mg of spray-dried powders were placed in a Breezhaler ® . The powders were dispersed at an airflow rate of 90 L/min for 2.7 s with a pressure drop of 3.5 kPa [20]. Before dispersion, the NGI plates were coated with the silicon lubricant (LPS Laboratories, Tucker, GA, USA).…”

Section: In Vitro Aerosol Performancementioning

confidence: 99%

“…The crystalline structures of the spray-dried powders and raw materials were studied by X-ray powder diffraction (X'Pert Powder; Malvern Panalytical Ltd., Malvern, UK) as previously reported [20]. About 4 mg of powder was spread compactly on the sample plate and subjected to Cu-Kα radiation at a current of 45 mA and voltage of 40 kV under ambient temperature.…”

Section: Powder X-ray Diffraction (Pxrd)mentioning

confidence: 99%

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Spray-Dried Powder Formulation of Capreomycin Designed for Inhaled Tuberculosis Therapy

et al. 2021

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Multi-drug-resistant tuberculosis (MDR-TB) is a huge public health problem. The treatment regimen of MDR-TB requires prolonged chemotherapy with multiple drugs including second-line anti-TB agents associated with severe adverse effects. Capreomycin, a polypeptide antibiotic, is the first choice of second-line anti-TB drugs in MDR-TB therapy. It requires repeated intramuscular or intravenous administration five times per week. Pulmonary drug delivery is non-invasive with the advantages of local targeting and reduced risk of systemic toxicity. In this study, inhaled dry powder formulation of capreomycin targeting the lung was developed using spray drying technique. Among the 16 formulations designed, the one containing 25% capreomycin (w/w) and spray-dried at an inlet temperature of 90 °C showed the best overall performance with the mass median aerodynamic diameter (MMAD) of 3.38 μm and a fine particle fraction (FPF) of around 65%. In the pharmacokinetic study in mice, drug concentration in the lungs was approximately 8-fold higher than the minimum inhibitory concentration (MIC) (1.25 to 2.5 µg/mL) for at least 24 h following intratracheal administration (20 mg/kg). Compared to intravenous injection, inhaled capreomycin showed significantly higher area under the curve, slower clearance and longer mean residence time in both the lungs and plasma.

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Inhaled Dry Powder Formulation of Tamibarotene, a Broad‐Spectrum Antiviral against Respiratory Viruses Including SARS‐CoV‐2 and Influenza Virus

Liao

Yuan

Cao

et al. 2021

Advanced Therapeutics

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In response to the epidemic and pandemic threats caused by emerging respiratory viral infections, a safe and efficient broad‐spectrum antiviral therapy at early onset of infection can significantly improve patients’ outcome. Inhaled dry powder is easy to administer and delivers antiviral agent directly to the primary site of infection, thereby minimizing systemic side effects. Here, spray freeze drying (SFD) technique is employed to formulate tamibarotene, a retinoid derivative with broad‐spectrum antiviral activity, as inhalable powder. The SFD tamibarotene powder exhibits desirable physicochemical and aerodynamic properties for inhalation. Pulmonary delivery of tamibarotene powder results in rapid absorption and higher bioavailability compared with intraperitoneal injection of unformulated drug in animals. More importantly, inhalation or intranasal delivery of SFD tamibarotene formulation displays broad‐spectrum antiviral activity against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), Middle East respiratory syndrome coronavirus, and pandemic 2009 influenza A virus (H1N1) in mouse and hamster models by targeting lower or upper airways, and the efficacy is comparable or superior to the commercially available antivirals remdesivir and zanamivir against specific virus. These results present a promising strategy to combat various respiratory viral infections including SARS‐CoV‐2 and influenza virus, or even co‐infection.

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Effect of formulation and inhaler parameters on the dispersion of spray freeze dried voriconazole particles

Cited by 29 publications

References 30 publications

Inhalable Protein Powder Prepared by Spray-Freeze-Drying Using Hydroxypropyl-β-Cyclodextrin as Excipient

Inhalable Protein Powder Prepared by Spray-Freeze-Drying Using Hydroxypropyl-β-Cyclodextrin as Excipient

Spray-Dried Powder Formulation of Capreomycin Designed for Inhaled Tuberculosis Therapy

Inhaled Dry Powder Formulation of Tamibarotene, a Broad‐Spectrum Antiviral against Respiratory Viruses Including SARS‐CoV‐2 and Influenza Virus

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