The Effect of Particle Size and Surface Roughness of Spray-Dried Bosentan Microparticles on Aerodynamic Performance for Dry Powder Inhalation

The purpose of this study was to prepare spray dried bosentan microparticles for dry powder inhaler and to characterize its physicochemical and aerodynamic properties. The microparticles were prepared from ethanol/water solutions containing bosentan using spray dryer. Three types of formulations (SD60, SD80, and SD100) depending on the various ethanol concentrations (60%, 80%, and 100%, respectively) were used. Bosentan microparticle formulations were characterized by scanning electron microscopy, powder X-ray diffraction, laser diffraction particle sizing, differential scanning calorimetry, Fourier-transform infrared spectroscopy, dissolution test, and in vitro aerodynamic performance using Andersen cascade impactor™ (ACI) system. In addition, particle image velocimetry (PIV) system was used for directly confirming the actual movement of the aerosolized particles. Bosentan microparticles resulted in formulations with various shapes, surface morphology, and particle size distributions. SD100 was a smooth surface with spherical morphology, SD80 was a rough surfaced with spherical morphology and SD60 was a rough surfaced with corrugated morphology. SD100, SD80, and SD60 showed significantly high drug release up to 1 h compared with raw bosentan. The aerodynamic size of SD80 and SD60 was 1.27 µm and SD100 was 6.95 µm. The microparticles with smaller particle size and a rough surface aerosolized better (%FPF: 63.07 ± 2.39 and 68.27 ± 8.99 for SD60 and SD80, respectively) than larger particle size and smooth surface microparticle (%FPF: 22.64 ± 11.50 for SD100).

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Co-Spray Dried Mannitol/Poly(amidoamine)-Doxorubicin Dry-Powder Inhaler Formulations for Lung Adenocarcinoma: Morphology, In Vitro Evaluation, and Aerodynamic Performance

AAPS PharmSciTech ◽

10.1208/s12249-017-0859-1 ◽

2017 ◽

Vol 19 (2) ◽

pp. 531-540 ◽

Cited By ~ 7

Author(s):

Qian Zhong

Keyword(s):

Lung Adenocarcinoma ◽

Dry Powder Inhaler ◽

Aerodynamic Performance ◽

Dry Powder ◽

In Vitro Evaluation ◽

Spray Dried ◽

Spray Dried Mannitol

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Development of a Carrier Free Dry Powder Inhalation Formulation of Ketotifen for Pulmonary Drug Delivery

Drug Research ◽

10.1055/a-0649-0814 ◽

2019 ◽

Vol 70 (01) ◽

pp. 26-32

Author(s):

Fariba Azari ◽

Saeed Ghanbarzadeh ◽

Rezvan Safdari ◽

Shadi Yaqoubi ◽

Khosro Adibkia ◽

...

Keyword(s):

Drug Delivery ◽

Spray Drying ◽

Dry Powder Inhaler ◽

Ammonium Bicarbonate ◽

Pulmonary Drug Delivery ◽

Water Mixture ◽

Dry Powder ◽

Scanning Calorimetry ◽

Aerodynamic Properties ◽

Systemic Treatments

Abstract Background Pulmonary drug delivery route is gaining much attention because it enables to target the active ingredients directly to lung both for local and systemic treatments, which maximize the therapeutic effect and minimize unwanted systemic toxicity. Dry powder inhaler (DPI) systems for asthma therapy have shown several merits to the other pulmonary delivery systems such as nebulizers and metered dose inhalers. Purpose The present study aims to develop and optimize a DPI formulation for Ketotifen fumarate through spray drying technique. Methods Particles size and morphology, crystallinity, and drug-excipient interaction of fabricated DPI formulations were evaluated by scanning electron microscopy, X-ray diffraction (XRD), differential scanning calorimetry (DSC), and Fourier Transform Infrared Spectroscopy methods, respectively. The aerosolization indexes and aerodynamic properties of dry powders were determined by next generation impactor. The powder flowability was assessed by measuring the Hausner ratio and compressibility index. Results Among solvent systems, ethanol-water mixture produced the most desirable powder property for inhalation after spray drying. Although co-spray dried formulations with ammonium bicarbonate resulted in the porous structure, it was not beneficial for DPI formulations due to the interaction with Ketotifen. DSC and XRD experiments proved the amorphous structure of prepared powders, which were stable for 12 months. Conclusion The results of this study demonstrate the potential of Ketotifen DPI formulation and pave a way to use it easily in an industrial scale.

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Inhalable Spray Dried Pro-Liposome Powder Containing Budesonide for Pulmonary Delivery

International Journal of Pharmaceutical Sciences and Nanotechnology ◽

10.37285/ijpsn.2021.14.4.3 ◽

2021 ◽

Vol 14 (4) ◽

pp. 5538-5548

Author(s):

Aliasgar J Kundawala ◽

Khushbu S Chauhan ◽

Harsha V Patel ◽

Swati K Kurtkoti

Keyword(s):

Drug Release ◽

Spray Drying ◽

Entrapment Efficiency ◽

Geometric Standard Deviation ◽

Drying Method ◽

Dry Powder ◽

Liposomal Drug ◽

Vesicle Size ◽

Aerodynamic Properties ◽

Spray Dried

Budesonide is an anti-asthmatic agent which is used to control the symptoms of asthma like bronchospasm, oedema. Drug delivered to lung through inhalation will provide systemic and local drug delivery at lower dose in chronic and acute diseases. Dry powder inhalers are the best choice for targeting the anti-asthmatic drugs through pulmonary route. The objective of the present study is to prepare inhalable lipid coated budesonide microparticles by spray drying method so effective delivery of budesonide to the lungs can be achieved. The microparticles in the form of dry powder were obtained by either spray drying liposomal drug suspension or lipid drug suspension. The liposomes were initially prepared by solvent evaporation method using Hydrogenated Soyabean Phosphatidylcholine and Cholesterol (1:1, 1:2, 2:1) as lipid carrier and then spray dried later with mannitol as bulking agent at different lipid to diluent ratio (1:1.25, 1:2.5 & 1:5). The liposomes and liposomal dry powder were evaluated for vesicle size, % entrapment efficiency, in vitro drug release studies, powder characteristics, aerosol performance and stability studies. The liposomes prepared showed vesicle size (2-8 µm), Entrapment efficiency (92.22%) at lipid: drug ratio of (2.5:1) and observed 80.41 % drug release in 24 hrs. Pro-liposomes prepared by spray drying of liposomal drug suspension (LSD1) showed emitted dose, mean mass aerodynamic diameter, geometric standard deviation and fine particle fraction of 99.01%, 3.12 µm, 1.78 and 43.5% along with good powder properties. The spray dried powder was found to be stable at 4 ± 2 °C & 65% ± 5 % RH. The inhalable microparticles containing Budesonide containing lipid dry powder was successfully prepared by spray drying method that showed good aerodynamic properties and stability with mannitol as diluent. The microparticles produced with this novel approach could deliver drug on target via inhalation route and also ease manufacture process at large scale in fewer production steps.

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Formulation, characterization and evaluation of nanoparticles based dry powder insufflation containing terbutaline sulphate and itraconazole for the treatment of asthma

International Journal of Research in Pharmaceutical Sciences ◽

10.26452/ijrps.v11i1.1859 ◽

2020 ◽

Vol 11 (1) ◽

pp. 567-580

Author(s):

Venugopalaiah Penabaka ◽

Kumar B ◽

Prasad N.B.L

Keyword(s):

Particle Size ◽

Size Distribution ◽

Bronchial Asthma ◽

Spherical Particles ◽

Dry Powder ◽

Terbutaline Sulphate ◽

Release Studies ◽

Physical Mixing ◽

Spray Dried

Many factors affect the pulmonary drug delivery and stability of the nanoparticles an acupuncture consisting of bronchial asthma. Present research envisages on the development of dry powder nanoparticles as insufflation a acupuncture consisting of bronchial asthma (allergy due to Aspergillus fumigatus) using physical mixing and spray drying. Different founding are prepared and characterized with suitable excipients like lactose and trehalose. The particle size distribution of nano milled and spray-dried particles of Terbutaline Sulphate and Itraconazole showed unimodal size distribution. The formulations prepared with trehalose as the carrier showed less Dv90, Dv50 and Dv10 values due to the fineness in the particles of trehalose when compared to lactose. The Dv50 and Dv10 values were in the range of mountains of 0.43-0.89 µm and 0.21–0.49 µm for all formulations, which shows the primary particle size in the nanometer scale. Smooth and nearly spherical particles were produced for spray-dried formulations when compared to milled formulations. Zeta potential comes across until be between +17±0.13 to +32±0.12, which explains the particles as moderately stable. MMAD values ranges from 3.19 µm to 4.78 µm for milled nanoparticles and 3.45 µm to 4.21 µm for spray-dried particles. Formulated nanoparticles exhibited good spreading properties, which will allow all the particles to deposition palmy profusion territories consisting of the lung. In-vitro drug release studies explains that spray-dried formulations of Terbutaline sulpahte and Itraconazole using lactose as excipients released the drug upto 98.9% and 99.1% in 180mts.

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Design of Spray-dried Porous Particles for Sugar-based Dry Powder Inhaler Formulation

YAKUGAKU ZASSHI ◽

10.1248/yakushi.18-00104 ◽

2018 ◽

Vol 138 (9) ◽

pp. 1163-1167 ◽

Cited By ~ 1

Author(s):

Kazunori Kadota

Keyword(s):

Dry Powder Inhaler ◽

Dry Powder ◽

Porous Particles ◽

Spray Dried

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Development of an Innovative, Carrier-Based Dry Powder Inhalation Formulation Containing Spray-Dried Meloxicam Potassium to Improve the In Vitro and In Silico Aerodynamic Properties

Pharmaceutics ◽

10.3390/pharmaceutics12060535 ◽

2020 ◽

Vol 12 (6) ◽

pp. 535 ◽

Cited By ~ 1

Author(s):

Edit Benke ◽

Árpád Farkas ◽

Piroska Szabó-Révész ◽

Rita Ambrus

Keyword(s):

In Silico ◽

Chronic Obstructive ◽

Dry Powder Inhalation ◽

Dry Powder ◽

Aerodynamic Properties ◽

Drug Concentrations ◽

Anti Inflammatory ◽

New Formulation ◽

Spray Dried

Most of the marketed dry powder inhalation (DPI) products are traditional, carrier-based formulations with low drug concentrations deposited in the lung. However, due to their advantageous properties, their development has become justified. In our present work, we developed an innovative, carrier-based DPI system, which is an interactive physical blend of a surface-modified carrier and a spray-dried drug with suitable shape and size for pulmonary application. Meloxicam potassium, a nonsteroidal anti-inflammatory drug (NSAID), was used as an active ingredient due to its local anti-inflammatory effect and ability to decrease the progression of cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD). The results of the in vitro and in silico investigations showed high lung deposition in the case of this new formulation, confirming that the interparticle interactions were changed favorably.

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