Optimizing the primary particle size distributions of pressurized metered dose inhalers by using inkjet spray drying for targeting desired regions of the lungs

Ehtezazi, Touraj; Davies, Michael J.; Seton, Linda; Morgan, Michael N.; Ross, Stacy; Martin, Graham D.; Hutchings, I.M.

doi:10.3109/03639045.2013.858741

Cited by 6 publications

(5 citation statements)

References 50 publications

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“…In contrast, the Qvar Easi-Breathe is a breath-actuated device that has been devised with a flow-triggered system driven by a spring that automatically releases the dose with the patient's inhalation. 27,28 It was designed to overcome the problem of coordination between actuation and breathing. Actuation of the aerosol occurs at low inhalation flows of approximately 20 L/min.…”

Section: Discussionmentioning

confidence: 99%

Bioavailability of Beclometasone From Two HFA-BDP Formulations With a Spacer

2019

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BACKGROUND: The drug delivery characteristics of each inhaler/spacer combination are unique. The spacer size as well as the presence of electrostatic charge greatly influence the inhaler dose emission and in vivo delivery. Using a previously developed urinary pharmacokinetic method, we have measured the relative lung and systemic bioavailability of beclometasone dipropionate (BDP) after inhalation from 2 hydrofluroalkane-beclometasone dipropionate (HFA-BDP) formulations when used with a spacer. METHODS: 12 healthy volunteers received 8 randomized doses, separated by 7 d, of inhaled of BDP with either the Clenil pressurized metered-dose inhaler (pMDI; 250 g) or the breath-actuated Qvar Easi-Breathe inhaler (100 g), used alone or with a spacer. The urinary amounts of BDP excreted and retained in the spacer were assayed using a liquid chromatographic mass spectrometer. The spacer was assessed after washing with a detergent solution that was either rinsed or not rinsed with water. In addition, the aerodynamic characterization of each inhaler/spacer combination was assessed using the Andersen Cascade Impactor operated at 28 L/min using a 4-L inhalation volume. The amount of BDP deposited in the induction port, spacer, and various Anderson Cascade Impactor stages were determined. RESULTS: The in vivo 30-min urinary excretion and the in vitro fine particle dose results were only slightly affected by adding the spacer to the Clenil pMDI or the Qvar Easi-Breathe inhaler. However, the spacer significantly reduced drug particle impaction in the oropharynx and minimized deposition in the gastrointestinal tract. Therefore, using spacers with BDP inhalers is associated with a more favorable therapeutic ratio because it has little effect on lung dose, but it significantly reduced throat deposition. An improved lung deposition was achieved with non-rinsed spacers compared to spacers rinsed with water. CONCLUSION: The difference in the BDP particle size between formulations as well as spacer size greatly affected drug deposition in different regions of the respiratory tract.

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Section: Discussionmentioning

confidence: 99%

Bioavailability of Beclometasone From Two HFA-BDP Formulations With a Spacer

2019

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“…1). Ehtezazi et al have reported the instrument design and setup in previous papers [20,21]. Briefly, the inkjet instrument was built using a glass capillary tube, which was already adjusted at one end to form a nozzle orifice of a selected size (50 μm and 20 μm).…”

Section: Liposome Preparation By Inkjet Methodsmentioning

confidence: 99%

“…Inkjet method produces uniform droplets from an inkjet device [18], and this technique has been used to produce uniform liposomes with a size in the range of 20-100 nm [19], uniform respirable particles for the formulation of pharmaceutical inhalers [20,21], and uniform porous polymer particles [22]. For the production of liposomes, the amphiphilic compounds were dissolved in ethanol and printed into an aqueous solution [19].…”

Section: Introductionmentioning

confidence: 99%

The effect of ethanol evaporation on the properties of inkjet produced liposomes

et al. 2020

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Background Inkjet method has been used to produce nano-sized liposomes with a uniform size distribution. However, following the production of liposomes by inkjet method, the solvent residue in the product could have a significant effect on the properties of the final liposomes. Objective This research paper aimed to find a suitable method to remove ethanol content and to study its effect on the properties of the final liposomal suspension. Method Egg phosphatidylcholine and lidocaine were dissolved in ethanol; and inkjet method at 80 kHz was applied to produce uniform droplets, which were deposited in an aqueous solution to form liposomes. Dry nitrogen gas flow, air-drying, and rotary evaporator were tested to remove the ethanol content. Liposome properties such as size, polydispersity index (PDI), and charge were screened before and after ethanol evaporation. Results Only rotary evaporator (at constant speed and room temperature for 2 h) removed all of the ethanol content, with a final drug entrapment efficiency (EE) of 29.44 ± 6.77%. This was higher than a conventional method. Furthermore, removing ethanol led to liposome size reduction from approximately 200 nm to less than 100 nm in most samples. Additionally, this increased the liposomal net charge, which contributed to maintain the uniform and narrow size distribution of liposomes. Conclusion Nano-sized liposomes were produced with a narrow PDI and higher EE compared to a conventional method by using an inkjet method. Moreover, rotary evaporator for 2 h reduced effectively the ethanol content, while maintaining the narrow size distribution.

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“…Inkjet printing methods have been utilised for pharmaceutical applications such as printing drug solutions on edible and conventional papers, manufacturing tablets, personalised medicine, preparation of bio‐adhesives, manufacture of spherical uniform particles and manufacture of uniform and custom shape particles …”

Section: Introductionmentioning

confidence: 99%

Development of High‐Throughput Glass Inkjet Devices for Pharmaceutical Applications

Ehtezazi

Dempster

Martin

et al. 2014

Journal of Pharmaceutical Sciences

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The application of the inkjet method to pharmaceutical products is promising. To make this realistic, not only does the throughput of this method need to be increased, but also the components should be inert to pharmaceutical preparations. We present designs of glass based inkjet devices that are capable of producing droplets at high rates. To achieve this, inkjet devices from capillary tubes were manufactured with orifice diameters of 5µm, 10µm and 20µm and were actuated with diaphragm piezoelectric disks. Also, a pressure capsule was formed by creating a manifold at a distance from the orifice tip. Placing the piezoelectric disk at 0.5 mm distance from the tip allowed formation of a jet at 3.2MHz in certain designs, but for a short period of time due to overheating. The length of the pressure capsule, its inlet diameter and the nozzle tip geometry were crucial to lower the required power. Actuating an inkjet device with 10µm orifice diameter comfortably at 900 kHz and drying the droplets from 1% salbutamol sulphate solution allowed formation of particles with diameters of 1.76±0.15µm and the geometric standard deviation of 1.08. In conclusion, optimising internal design of glass inkjet devices allowed production of high throughput droplet ejectors.

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Optimizing the primary particle size distributions of pressurized metered dose inhalers by using inkjet spray drying for targeting desired regions of the lungs

Cited by 6 publications

References 50 publications

Bioavailability of Beclometasone From Two HFA-BDP Formulations With a Spacer

Bioavailability of Beclometasone From Two HFA-BDP Formulations With a Spacer

The effect of ethanol evaporation on the properties of inkjet produced liposomes

Development of High‐Throughput Glass Inkjet Devices for Pharmaceutical Applications

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