Nano Spray Drying of Pharmaceuticals · Introduction to nano spray drying technology Concept of...
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Nano Spray Drying of Pharmaceuticals Dr. Cordin Arpagaus NTB Interstate University of Applied Sciences of Technology Buchs, Switzerland IDS’2018 – 21st International Drying Symposium València, Spain, 11-14 September 2018 Paper #7356 INSTITUTE FOR ENERGY SYSTEMS
Transcript of Nano Spray Drying of Pharmaceuticals · Introduction to nano spray drying technology Concept of...
Nano Spray Drying of Pharmaceuticals
Dr. Cordin Arpagaus
NTB Interstate University of Applied Sciences of Technology Buchs, Switzerland
IDS’2018 – 21st International Drying Symposium València, Spain, 11-14 September 2018Paper #7356
19INSTITUTE FOR ENERGY SYSTEMS
IDS‘2018 [email protected] 2
Outline
Introduction to nano spray drying technology Concept of nano spray drying & equipment components (e.g. nozzle, particle collector)
Main process parameters & formulation variables
Influence on powder properties (e.g. particle size & morphology, yield, encapsulationefficiency, drug loading) & optimal process conditions
Applications of nano spray dried pharmaceuticals Application areas & drug administration routes
Discussion of different pharmaceutical applications
Conclusions
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Introduction to nano spray drying technology
Elements of a nano spray dryerVibrating mesh technology to produce an ultrafine spray
(Arpagaus et al. 2017)
Efficient electrostatic powder collector to extend the size spectrum of separable particles to the nanoscale.
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Introduction to nano spray drying technology
Process parameters & formulation variables
Adjustable process parameters and formulation variablesResulting outputs (Arpagaus et al. 2017)
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Introduction to nano spray drying technology
Nano spray drying offers flexibility for formulation –Influence of process parameters on particle properties
strong, weak increasing/decreasing influence, - minimal or no influence
(Arpagaus et al. 2017)
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Introduction to nano spray drying technology
Influence of gas temperature, gas flow rate, and feed rate on drying conditions
(Arpagaus et al. 2017)
for acqueous fluids
Typical drying temperaturesfor other solvents:
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Introduction to nano spray drying technology
A compromise needs to be found between feed rate (productivity), solid concentration, and particle size
(Arpagaus et al. 2017)
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Introduction to nano spray drying technology
The achievable particle sizes range is below 5 µm –The submicron region is reached at diluted concentrations
(Arpagaus et al. 2017)
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Introduction to nano spray drying technology
Particle size increases with spray mesh size
Example: Bovine serum albumin at 1% (w/v) solid concentration
7.0 μm
Mean particle size: 0.7 μm 1.7 μm 2.6 μm
5.5 μm4.0 μm
(Lee et al. 2011)
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Introduction to nano spray drying technology
Nano spray drying offers flexibility for formulation –Effects on particle size & morphology
𝑑𝑑𝑃𝑃 =3 𝐶𝐶𝜌𝜌𝑑𝑑𝐷𝐷 𝑃𝑃𝑃𝑃 =
𝑘𝑘8𝐷𝐷
𝑑𝑑𝑃𝑃: Geometric diameter of the spray dried particle
𝐶𝐶: Solid concentration in solution𝑑𝑑𝐷𝐷: Atomized droplet diameter𝜌𝜌: Particle density
𝑃𝑃𝑃𝑃 < 1: Particles are likely solid𝑃𝑃𝑃𝑃 > 1: Particles are low density
𝑃𝑃𝑃𝑃: Peclet number𝑘𝑘: Droplet evaporation rate𝐷𝐷: Diffusion motion
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Introduction to nano spray drying technology
Examples of particle morphologies
Salbutamol sulfate Albuterol in mannitol
Trehalose
Cyclosporin* in PLGA
β-galactosidase Bovine serum albumin
(Arpagaus et al. 2017)*Cyclosporin: Immune system suppressing drug (used in transplantations)
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Introduction to nano spray drying technology
A huge versatility of particle morphologies
(Arpagaus et al. 2017)
Composites
Hollow particles and capsules
Doughnut shape
Shriveled/wrinkled particlesSpherical particles
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Introduction to nano spray drying technology
Nano spray drying in the lab
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Applications of nano spray dried pharmaceuticlas
Examples of administration routes
Pulmonary(by inhalation)
Oral(gastrointestinal)
Intravenous(blood
circulation)
Topical
Ophthalmic
Intravesical(bladder)
Intraperitoneal
Cerebral
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Applications of nano spray dried pharmaceuticals
General particle design strategies –Particle morphologies and size range
General design strategies: Size reduction
Composite materials withnano/micro particles structure
Doping and functionalization
Tuning particle morphology
Formation of coatings orshells around active materials
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Applications of nano spray dried pharmaceuticals
Increasing trend of the research activity in this field
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Applications of nano spray dried pharmaceuticlas
What are the application areas?
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dichloromethane (Beck-Broichsitter et al. 2012, Bege et al. 2013, Dahili et al. 2015, Dahili and Feczkó 2015, Draheim et al. 2015, Panda et al. 2014, Schafroth et al. 2012),
acetone (Beber et al. 2014, Beck-Broichsitter et al. 2015b, Draheim et al. 2015, Durli et al. 2014, Fontana et al. 2014, Gu et al. 2015, Li et al. 2010, Perecin et al. 2015),
ethanol (Baba and Nishida 2013, 2012, Bürki et al. 2011, Maged et al. 2017, Zellnitz et al. 2015a),
methanol (Basran 2017, Öztürk et al. 2017, 2015, Schmid 2011, Suryaprakash et al. 2014),
acetonitrile (Amsalem et al. 2017, Denora et al. 2016),
ethylacetate (Draheim et al. 2015) and mixtures thereof with water (Aquino et al. 2014, Dimer et al. 2015a, Kaewjan and Srichana 2016, Martena et al. 2012a, Schoubben et al. 2015, 2013a; Son et al., 2013b).
Applications of nano spray dried pharmaceuticals
The selection of the organic solvent is based on drugsolubilization and the encapsulating wall materials. Typical solvents applied are:
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Applications of nano spray dried pharmaceuticlas
Some encapsulation wall materials and excipients
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Applications of nano spray dried pharmaceuticlas
Submicron particles are produced!
(Arpagaus et al. 2017)
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Applications of nano spray dried pharmaceuticals
High encapsulation efficiencies >95% and drug loadings
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Applications of nano spray dried pharmaceuticlas
Uniquely high yields of 90% are achieved for small sample amounts from 10 mg to 2.5 g
(Arpagaus et al. 2017)
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Applications on nano spray dried pharmaceuticlas
A list of performed pharmaceutical applications
asthma (e.g. salbutamol, terbutaline, or fluticasone), inflammation (e.g. dexamethasone and azithromycin, or pain and fever reducer
indomethacin and nimesulide), cystic fibrosis (e.g. antibacterial dexketoprofen in Kollidon and Eudragit nanoparticles, or
azithromycin in leucine), diabetes (e.g. sitagliptin, vildagliptin, and metformin in mucoadhesive Carbopol and gelatin), pulmonary arterial hypertension (e.g. resveratrol in poly(caprolactone), or sildenafil in
PLGA), tuberculosis (e.g. capreomycin or pyrazinamide in L-leucine, or ethambutol mixed with
chitosan carrier particles), Alzheimer's and Parkinson's diseases (e.g. nanocrystals of calpain inhibitor steroids), breast cancer (e.g. simvastatin loaded PLGA particles), or lung cancer (e.g. methotrexate,
carboplatin in gelatine, or paclitaxel), bacterial infections (e.g. amoxicillin, ciprofloxacin, gatifloxacin, clarithromycin, or
levofloxacin), fungal infections (e.g. antifungal griseovulfin) ophthalmic disorders (e.g. calpain inhibitor nanocrystals or dirithromycin incorporated in
Kollidon), high blood pressure (e.g. nimodipine in PLGA or pure nicergoline nanoparticles), congestive heart failure and edema (e.g. diuretic furosemide).
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It is a versatile technology with a wide range of applications.
Main application trends are in the areas of pulmonary drug delivery, nanotherapeutics, the encapsulation of nanoemulsions with poorly water-soluble active ingredients and the formulation of nanocrystals for a higher bioavailability.
Submicron particles formed with diluted solutions of 0.1 to 1% (w/v).
Encapsulation efficiencies of over 95%, adjustable drug loadings, stability, protection, dry powder form.
High yields enable an economical use of valuable drugs.
An optimized set of parameters can be found.
There is an increasing need for scale-up.
Conclusions
Nano spray drying of pharmaceuticals
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Literature on nano spray drying of pharmaceuticals
Arpagaus C., Collenberg A., Rütti D., Assadpour E., Jafari S.M.: Nano Spray Drying forEncapsulation of Pharmaceuticals, International Journal of Pharmaceutics, 2018, 546, 1–2, 194-214.
Arpagaus, C., John, Ph., Collenberg, A., Rütti, D.: Chapter 10: Nanocapsules formation bynano spray drying, in: Nanoencapsulation Technologies for the Food and NeutraceuticalIndustries, edited by Seid Mahdi Jafari, ISBN: 978-0-12-809426-5, London, ElsevierAcademic Press, 2017, 346-401.
Arpagaus C., Rütti D., Meuri M.: Chapter 17: Enhanced solubility of poorly soluble drugsvia spray drying, in: Drug delivery strategies for Poorly Water-Soluble Drugs, edited byDouroumis D. and Fahr A., ISBN: 978-0-470-71197-2, Chichester, West Sussex, John Wiley & Sons, 2012, 551-586.
Arpagaus C.: A Novel Laboratory-Scale Spray Dryer to Produce Nanoparticles, DryingTechnology, 2012, 30, 10, 1113-1121.
Arpagaus, C., Schafroth, N.: Spray dried biodegradable polymers for controlled drugdelivery systems, Industrial Pharmacy, 2011, 32, 7-10.
Thank you for your attention
Contact details:
Dr. Cordin ArpagausNTB University of Applied Sciences ofTechnology Buchs, Switzerland
[email protected]. +41 81 377 94 34www.ntb.ch/en/team/cordin-arpagaus
INSTITUTE FOR ENERGY SYSTEMS
