Implementation of design of experiments approach for the micronization of a drug with a high brittle–ductile transition particle diameter

Yazdi, Ashkan K.

doi:10.1080/03639045.2016.1253727

Cited by 10 publications

(4 citation statements)

References 21 publications

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“…A lab-scale Aljet air jet mill (also known as a model 00 Jet-O-Mizer, Fluid Energy, Telford, PA) was used to micronize CFZ (Sigma; Lot: SLBL8945 V) to a particle size distribution within the respirable range of 0.5–5 μm. Based upon previously reported methods − for air jet milling for DPI formulations in our lab, the air jet mill was set at 75 psi grind pressure, 65 psi feed pressure, and 1 g/min feed rate. Approximately 3–4.5 g of CFZ was milled per batch.…”

Section: Methodsmentioning

confidence: 99%

Excipient-Free Pulmonary Delivery and Macrophage Targeting of Clofazimine via Air Jet Micronization

2017

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Clofazimine (CFZ) is highly active against mycobacterium, including resistant Mycobacterium tuberculosis, but its therapeutic efficacy via the oral route is limited by severe adverse effects, poor aqueous solubility, and slow onset of action. Pulmonary delivery of CFZ is an attractive alternative to target mycobacterium-harboring alveolar macrophages. This study explores the use of air jet milling to develop a respirable, cost-effective CFZ formulation. Jet milled CFZ was readily dispersed from an off-the-shelf dry powder inhaler without the need for additional excipients or carrier particles. Additionally, milled CFZ was internalized by J774.A1 alveolar macrophages within 8 h, with evidence of intracellular biotransformation of the CFZ crystals and macrophage sequestration by 24 h. Less macrophage toxicity was noted in comparison to solubilized drug. Compared to macrophage uptake rate, dissolution of milled CFZ was limited, thereby potentially reducing systemic absorption and subsequent side effects. These results suggest that jet milling is an effective manufacturing method in the development of a CFZ formulation for pulmonary delivery and alveolar macrophage targeting.

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Section: Methodsmentioning

confidence: 99%

Excipient-Free Pulmonary Delivery and Macrophage Targeting of Clofazimine via Air Jet Micronization

2017

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“…Each API must be evaluated itself for feasibility, and we have not yet scaled micronized TIG to these instruments. Typically, low fill weights exacerbate difficulty in achieving capsule target weight uniformity; however, in the case of high dose powders some of this concern is reduced. − In addition, the observed lack of flow rate-dependent changes and efficient dispersion of micronized TIG at lower pressures indicates lack of cohesivity, which is likely to translate to good powder handling as well as makes it a promising drug to be administered via inhalation, which is robust to changes in patient characteristics. Future studies will evaluate scaling powder filling to capsules.…”

Section: Discussionmentioning

confidence: 99%

Inhalable Excipient-Free Dry Powder of Tigecycline for the Treatment of Pulmonary Infections

Nair,

Smyth

2023

Mol. Pharmaceutics

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“…Because of its therapeutic importance for pulmonary lung infections, rifampicin was chosen as a model medication for carrier-free delivery. Rifampicin was milled using a Fluid Energy Model 00 Jet-O-Mizer air jet mill at 75 PSI grind pressure, 65 PSI feed pressure, and 1 g/min feed rate to produce particles within the respirable range ( 27 ). The obtained formulations were kept in a desiccator at room temperature.…”

Section: Methodsmentioning

confidence: 99%

Comparison of HPMC Inhalation-Grade Capsules and Their Effect on Aerosol Performance Using Budesonide and Rifampicin DPI Formulations

et al. 2022

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Despite the fact that capsules play an important role in many dry powder inhalation (DPI) systems, few studies have been conducted to investigate the capsules’ interactions with respirable powders. The effect of four commercially available hydroxypropyl methylcellulose (HPMC)inhalation-grade capsule types on the aerosol performance of two model DPI formulations (lactose carrier and a carrier-free formulation) at two different pressure drops was investigated in this study. There were no statistically significant differences in performance between capsules by using the carrier-based formulation. However, there were some differences between the capsules used for the carrier-free rifampicin formulation. At 2-kPa pressure drop conditions, Embocaps® VG capsules had a higher mean emitted fraction (EF) (89.86%) and a lower mean mass median aerodynamic diameter (MMAD) (4.19 µm) than Vcaps® (Capsugel) (85.54%, 5.10 µm) and Quali-V® I (Qualicaps) (85.01%, 5.09 µm), but no significant performance differences between Embocaps® and ACGcaps™ HI. Moreover, Embocaps® VG capsules exhibited a higher mean respirable fraction (RF)/fine particle fraction (FPF) with a 3-µm–sized cutoff (RF/FPF < 3 µm ) (33.05%/35.36%) against Quali-V® I (28.16%/31.75%) ( P < 0.05), and a higher RF/FPF with a 5-µm–sized cutoff (RF/FPF < 5 µm ) (49.15%/52.57%) versus ACGcaps™ HI (38.88%/41.99%) ( P < 0.01) at 4-kPa pressure drop condition. Aerosol performance variability, pierced-flap detachment, as well as capsule hardness and stiffness, may all influence capsule type selection in a carrier-based formulation. The capsule type influenced EF, RF, FPF, and MMAD in the carrier-free formulation.

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Implementation of design of experiments approach for the micronization of a drug with a high brittle–ductile transition particle diameter

Abstract: The optimization of a single-step air-jet milling of IBU using the DoE approach elucidated the optimal milling conditions, which were used to micronize IND using the optimized milling conditions.

Cited by 10 publications

References 21 publications

Excipient-Free Pulmonary Delivery and Macrophage Targeting of Clofazimine via Air Jet Micronization

Excipient-Free Pulmonary Delivery and Macrophage Targeting of Clofazimine via Air Jet Micronization

Inhalable Excipient-Free Dry Powder of Tigecycline for the Treatment of Pulmonary Infections

Comparison of HPMC Inhalation-Grade Capsules and Their Effect on Aerosol Performance Using Budesonide and Rifampicin DPI Formulations

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