Development of excipients free inhalable co-spray-dried tobramycin and diclofenac formulations for cystic fibrosis using two and three fluid nozzles

Marasini, Nirmal; Sheikh, Zara; Wong, Chun Yj; Hosseini, Maryam; Spicer, Patrick T.; Young, Paul M.; Ong, Hui Xin; Traini, Daniela

doi:10.1016/j.ijpharm.2022.121989

Cited by 10 publications

(9 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The choice of nozzle resulted in significant differences in the Physico-chemical characteristics between the 2FN and 3FN formulations. These altered characteristics were due to differences in feed preparation and nozzle geometry mediated mechanisms of particle formation, potentially changing drug distribution patterns within the particles, intrinsic drug solubility and dissolution rates, thus altering the therapeutic efficacy of NF [ 12 , 13 , 14 , 15 ]. Spray-drying using 2FN requires a mixture of a drug (NF) and excipient (HPMC) fed into the 2FN nozzle via a single channel, resulting in particles comprised of NF dispersed throughout HPMC.…”

Section: Discussionmentioning

confidence: 99%

“…Powder density was determined in triplicate using a previously reported method [ 14 ]. The powder equivalent of 1 g of sample was placed in a 5 mL measuring cylinder and the volume was recorded as the bulk volume.…”

Section: Methodsmentioning

confidence: 99%

“…Several factors, including feed flow rate, inlet and outlet temperature, aqueous/organic contents, drug/carrier physicochemical properties and nozzle size impact the final characteristics of the spray-dried powder [ 12 ]. In particular, the type of nozzle used to atomise the feed (drug solution/suspension) plays a significant role in the patterns of drug distribution in the dried particles [ 12 , 13 , 14 , 15 ]. This is especially significant as the drug distribution within the particles then dictates the drug dissolution characteristics [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

“…In particular, the type of nozzle used to atomise the feed (drug solution/suspension) plays a significant role in the patterns of drug distribution in the dried particles [ 12 , 13 , 14 , 15 ]. This is especially significant as the drug distribution within the particles then dictates the drug dissolution characteristics [ 14 ]. A variety of atomising nozzles are used in spray drying, such as rotary, hydraulic (one-fluid), ultrasonic and pneumatic (two-fluid or three-fluid) nozzles [ 12 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

“…The two-fluid nozzle (2FN) is the most commonly used pneumatic nozzle and functions by ejecting a stream of the drug/carrier solution from a single channel. This method of spray drying produces uniformly dispersed drugs within and on the particle surface [ 14 , 16 , 17 ]. Conversely, a three-fluid nozzle/3FN offers distinct advantages in terms of spraying patterns as both the drug/carrier solution can be separated into aqueous and organic phases that are simultaneously sprayed from an inner and an outer channel.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Development of Inhalable Spray Dried Nitrofurantoin Formulations for the Treatment of Emphysema

et al. 2022

Self Cite

View full text Add to dashboard Cite

A central characteristic of emphysematous progression is the continuous destruction of the lung extracellular matrix (ECM). Current treatments for emphysema have only addressed symptoms rather than preventing or reversing the loss of lung ECM. Nitrofurantoin (NF) is an antibiotic that has the potential to induce lung fibrosis as a side effect upon oral administration. Our study aims to repurpose NF as an inhalable therapeutic strategy to upregulate ECM expression, thereby reversing the disease progression within the emphysematous lung. Spray-dried (SD) formulations of NF were prepared in conjunction with a two-fluid nozzle (2FN) and three-fluid nozzle (3FN) using hydroxypropyl methylcellulose (HPMC) and NF at 1:1 w/w. The formulations were characterized for their physicochemical properties (particle size, morphology, solid-state characteristics, aerodynamic behaviour, and dissolution properties) and characterized in vitro with efficacy studies on human lung fibroblasts. The 2FN formulation displayed a mass mean aerodynamic diameter (MMAD) of 1.8 ± 0.05 µm and fine particle fraction (FPF) of 87.4 ± 2.8% with significantly greater deposition predicted in the lower lung region compared to the 3FN formulation (MMAD: 4.4 ± 0.4 µm; FPF: 40 ± 5.8%). Furthermore, drug dissolution studies showed that NF released from the 2FN formulation after 3 h was significantly higher (55.7%) as compared to the 3FN formulation (42.4%). Importantly, efficacy studies in human lung fibroblasts showed that the 2FN formulation induced significantly enhanced ECM protein expression levels of periostin and Type IV Collagen (203.2% and 84.2% increase, respectively) compared to untreated cells, while 3FN formulations induced only a 172.5% increase in periostin and a 38.1% increase in type IV collagen. In conclusion, our study highlights the influence of nozzle choice in inhalable spray-dried formulations and supports the feasibility of using SD NF prepared using 2FN as a potential inhalable therapeutic agent to upregulate ECM protein production.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Development of Inhalable Spray Dried Nitrofurantoin Formulations for the Treatment of Emphysema

et al. 2022

Self Cite

View full text Add to dashboard Cite

show abstract

Insulin Delivery to the Brain via the Nasal Route: Unraveling the Potential for Alzheimer's Disease Therapy

Wong,

Baldelli,

Hoyos

et al. 2024

Drug Deliv. and Transl. Res.

Self Cite

View full text Add to dashboard Cite

This comprehensive review delves into the potential of intranasal insulin delivery for managing Alzheimer's Disease (AD) while exploring the connection between AD and diabetes mellitus (DM). Both conditions share features of insulin signalling dysregulation and oxidative stress that accelerate inflammatory response. Given the physiological barriers to brain drug delivery, including the blood-brain barrier, intranasal administration emerges as a non-invasive alternative. Notably, intranasal insulin has shown neuroprotective effects, impacting Aβ clearance, tau phosphorylation, and synaptic plasticity. In preclinical studies and clinical trials, intranasally administered insulin achieved rapid and extensive distribution throughout the brain, with optimal formulations exhibiting minimal systemic circulation. The detailed mechanism of insulin transport through the nose-to-brain pathway is elucidated in the review, emphasizing the role of olfactory and trigeminal nerves. Despite promising prospects, challenges in delivering protein drugs from the nasal cavity to the brain remain, including enzymes, tight junctions, mucociliary clearance, and precise drug deposition, which hinder its translation to clinical settings. The review encompasses a discussion of the strategies to enhance the intranasal delivery of therapeutic proteins, such as tight junction modulators, cell-penetrating peptides, and nano-drug carrier systems. Moreover, successful translation of nose-to-brain drug delivery necessitates a holistic understanding of drug transport mechanisms, brain anatomy, and nasal formulation optimization. To date, no intranasal insulin formulation has received regulatory approval for AD treatment. Future research should address challenges related to drug absorption, nasal deposition, and the long-term effects of intranasal insulin. In this context, the evaluation of administration devices for nose-to-brain drug delivery becomes crucial in ensuring precise drug deposition patterns and enhancing bioavailability. Graphical Abstract Drug transport mechanism through the nose-to-brain pathway using the olfactory and trigeminal nerves (major pathway) and from the bloodstream through BBB (minor pathway).

show abstract

Updates on applications of low-viscosity grade Hydroxypropyl methylcellulose in coprocessing for improvement of physical properties of pharmaceutical powders

Jin

Yang

et al. 2023

Carbohydrate Polymers

View full text Add to dashboard Cite

Development of excipients free inhalable co-spray-dried tobramycin and diclofenac formulations for cystic fibrosis using two and three fluid nozzles

Cited by 10 publications

References 28 publications

Development of Inhalable Spray Dried Nitrofurantoin Formulations for the Treatment of Emphysema

Development of Inhalable Spray Dried Nitrofurantoin Formulations for the Treatment of Emphysema

Insulin Delivery to the Brain via the Nasal Route: Unraveling the Potential for Alzheimer's Disease Therapy

Updates on applications of low-viscosity grade Hydroxypropyl methylcellulose in coprocessing for improvement of physical properties of pharmaceutical powders

Contact Info

Product

Resources

About