Nasal Spray Formulations Emulsified with Ultrasound

Nasal sprays and mouth sprays are widely used drug administering solutions to apply active ingredients to the respiratory mucosa. Ultrasonic emulsification is a highly efficient and reliable technique to produce highly efficacious nasal and mouth spays with very high bioavailability, absorption rate and tolerability. As well-established emulsion technique, ultrasonicators are readily available as benchtop and industrial systems.

Ultrasonic Homogenizing of Active Pharmaceutical Ingredients

Ultrasonic homogenizers are highly efficient in creating micro- and nano-sized emulsions, which allow to formulate pharmaceuticals and care products with superior functionalities, including increased bioavailability, improved drug solubilization and long term stability, as wll as better absorption rate and tolerability. Due to its efficient mixing performance, ultrasonic dispersing and emulsifying is a widely aplied technique in the production process of nasal sprays, mouth sprays, mouth washes and mouth rinses. These products, which are administered to nose and mouth, are used to disinfect the mucosal tissue and to administer active pharaceutical ingredients via the mucosal lining, which is known for its high absorption capacity of active molecules.

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Ultrasonic nanoemulsification is an efficacious technique for the production of pharmaceutical formulations.

Ultrasonicator for the formulation of pharmaceuticals such as nasal sprays, tinctures and mouth rinses.

Ultrasonic emulsification using the UP400St, e.g., for the formulation of nasal sprays and mouth washes.Commonly active ingredients in antimicrobial nasal sprays and mouthwashes include pharmaceutical compounds (e.g, with antimicrobial, anti-inflammatory, desinfecting or congestal effects) as well as plant-derived molecules with antimicrobial or caring properties (e.g., artemisinin, curcumin, frankincense, vitamin C, eugenol, aloe vera etc.). High-performance ultrasonicators reliably disperse and emulsify the ingredients of nasal sprays, mouth washes, and mouth washes. The ultrasonic nanosizing and nano-encapsulation of the product ingredients results in a homogeneous and efficacious formulation with high bioavailability and long-term stability.

Ultrasonication can be also used for the manufacturing of nasal and mouth sprays, e.g., against the common cold, SARS-Cov-2 and other respiratory infections.
For instance, iota-carrageenan (such as carrageloseTM) and hypromellose are active ingredients, which show promising effects to give sterility / immunity against SARS-CoV-2 and other respiratory viruses for several hours.

Carragenans are bio-polymers, which are derived from marine macroalgae (seaweed). Scientific studies show that carrageenans used as in nasal and mouth sprays as well as lozenges have the potential of first line defense to inhibit the infection and transmission of SARS-CoV-2. The research of Fröba et al. (2021) shows that carrageenans such as iota-carrageenan might be “effective for prophylaxis and treatment of SARS-CoV-2 infections independent of the present and potentially future variants.” Ultrasonication is well known for its reliable dispersion efficiency of carrageenans, since carragenan is a common additive used e.g., as mucoadhesive in pharmaceuticals and as stabilizer in food and cosmetic products. For instance, K-carrageenan is successfully used as stabilizer in the production of o/w-emulsions.
Click here to read more about carrageenan extraction from algae using ultrasonication!

Ultrasonic processor UIP2000hdT (2kW) with stirred batch reactor is used for the formulation of pharmaceutical products such as nasal sprays, mouth rinses, tinctures, eye drops etc.

Ultrasonic processor UIP2000hdT (2kW) with batch reactor for the formulation of therapeutics.

Ultrasonic Formulation of Hybrid-Carrangeenan Nanogel

Shows the UP200Ht ultrasonic homogenizer mounted to a lab stand, emulsifying in a lab beaker.Rodriguez et al. (2020) report the successful ultrasonic synthesis of a hybrid kappa-/iota-carrageenan micro- and nanogels using the Hielscher device UP200St (see picture left). “KCl was used as a cross-linking agent and Tween 80 was used as surfactant. The micro- and nanogels suspended in water were found to simultaneously exhibit a lower diameter, and a lower swelling ratio with higher Tween 80 content. The micro- and nanogel suspension yields a zeta potential value of −50.5 mV, superior to values reported elsewhere for pure κ- or ι-carrageenan micro- and nanogels. The high stability was attributed to the high hydrophile-lipophile balance (HLB = 15) value of Tween 80. These results suggest that hybrid κ/ι-carrageenan micro- and nanogels are promising candidates for smart therapeutics applications.”
Ultrasonic device used: Hielscher UP200St

Ultrasonic Emulsification
Another promising polymer for the prophylaxis against SARS-Cov-2 and other respiratory infections is hypromellose (hydroxypropyl methylcellulose), which is a semisynthetic, inert, viscoelastic polymer used as eye drops, as excipient and as controlled-delivery component in oral medicaments. Hypromellose is already used in a variety of commercially available products and can be efficiently emulsified using sonication.

Ultrasonic Formulation of Intranasal Vaccines and Drugs

Sonication has been also successfully used in the production of intranasal vaccines (e.g., against S. pneumoniae).
Read more about ultrasonically formulated intranasal vaccines!

Ultrasonic Emulsifiers for the Manufacturing of Pharmaceuticals and Care Products

Ultrasonic processing is widely used to produce pharmaceuticals such as nano-formulated drugs, vaccines, as well as drug carriers such as nano-emulsions and liposomes. Hielscher Ultrasonics offers the full range of ultrasonic processors from lab and bench-top ultrasonicators to pilot and fully-industrial systems.

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Highest Quality – Designed & Manufactured in Germany

The sophisticated hardware and smart software of Hielscher ultrasonicators are designed to guarantee reliable ultrasonic processing such as nanoemulsions, API synthesis, liposome formulations, and nano-dispersions with reproducible outcomes and in user-friendly manner.
Hielscher Ultrasonics systems are used worldwide in the oroduction of well-known pharmaceutical producers. Proven to be reliable for the synthesis of high yields of high-quality products, Hielscher ultrasonicators are not only used on laboratory scale, but mostly in the industrial production of pharmaceuticals. Due to their robustness and low maintenance, Hielscher ultrasonic processors can be easily installed, operated and monitored.

Automatic Data Protocolling

Hielscher ultrasonicators can be remotely controlled via browser control. Sonication parameters can be monitored and adjusted precisely to the process requirements.In order to fulfil the production standards of pharmaceuticals, production processes must be detailed monitored and recorded. Hielscher Ultrasonics digital ultrasonic deviced feature an automatic data protocolling. Due to this smart feature, all important process parameters such as ultrasonic energy (total and net energy), temperature, pressure and time are automatically stored onto a built-in SD-card as soon as the device is switched on.
Process monitoring and data recording are important for continuous process standardization and product quality. By accessing the automatically recorded process data, you can revise previous sonication runs and evaluate the outcome.
Another user-friendly feature is the browser remote control of our digital ultrasonic systems. Via remote browser control you can start, stop, adjust and monitor your ultrasonic processor remotely from anywhere.
Want to learn more about the advantages of ultrasonic pharmaceutical production?Contact us now to discuss your pharmaceutical manufacturing process! Our well-experienced staff will be glad to share more information about ultrasonic pharma applications (e.g. nanoemulsification, liposomes, crystallization, dispersion), ultrasonic systems and pricing!

Why Hielscher Ultrasonics?

  • high performance ultrasound
  • state-of-the-art technology
  • reproducibility / repeatability
  • reliability & robustness
  • batch & inline
  • for any volume
  • intelligent software
  • smart features (e.g., data protocolling)
  • CIP (clean-in-place) / SIP (sterilize-in-place)

The table below gives you an indication of the approximate processing capacity of our ultrasonicators:

Batch Volume Flow Rate Recommended Devices
1 to 500mL 10 to 200mL/min UP100H
10 to 2000mL 20 to 400mL/min UP200Ht, UP400St
0.1 to 20L 0.2 to 4L/min UIP2000hdT
10 to 100L 2 to 10L/min UIP4000hdT
n.a. 10 to 100L/min UIP16000
n.a. larger cluster of UIP16000

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Ultrasonic high-shear homogenizers are used in lab, bench-top, pilot and industrial processing.

Hielscher Ultrasonics manufactures high-performance ultrasonic homogenizers for mixing applications, dispersion, emulsification and extraction on lab, pilot and industrial scale.



Literature / References


High performance ultrasonics! Hielscher's product range covers the full spectrum from the compact lab ultrasonicator over bench-top units to full-industrial ultrasonic systems.

Hielscher Ultrasonics manufactures high-performance ultrasonic homogenizers from lab to industrial size.