Improved Remdesivir Solubility by Sonication

Remdesivir (GS-5734) is an anti-viral drug, which is under research for treating the Ebola virus disease and COVID-19, which is caused by the Sars-CoV-2 coronavirus. Remdesivir is pharmaceutical solution, which is administered intravenously. Whilst short ultrasonic dissolving alone enhances the solubility of remdesivir and improves its formulation, ultrasonic complexation of remdesivir within cyclodextrin complexes is a promising technique to overcome the dissolubility issues of remdesivir, which makes the drug more bioavailable.

Ultrasonic Complexation of Remdesivir into Cyclodextrin Drug Carriers

Sulfobutyl-ether beta-cyclodextrin (SBE-β-CD) is used as an excipient or a formulating agent to increase the solubility of poorly soluble agents. Research suggests that the complexation of remdesivir into SBE-β-CD complexes will improve the solubility of remdesivir significantly improving thereby its absorption rate and bioavailability.

Formulations for “in vitro” research:

1. H₂O : 250 mg/mL – requires ultrasonication for solubilisation
2. Dimethyl sulfoxide (DMSO) : 5.625 mg/mL – requires ultrasonication + heating for solubilisation

Formulations for “in vivo” research:

1. Add each solvent one by one: 10% DMSO, 40% PEG300, 5% Tween 80, 45% saline + sonication
   Solubility: ≥ 2.17 mg/mL (3.60 mM); Clear solution
2. Add each solvent one by one: 10% DMSO, 90% (20% Sulfobutyl-ether beta-cyclodextrin (SBE-β-CD) in saline) + sonication
   Solubility: ≥ 2.17 mg/mL (3.60 mM); Clear solution
3. Add each solvent one by one: 10% DMSO, 90% corn oil + sonication
   Solubility: ≥ 2.17 mg/mL (3.60 mM); Clear solution

Ultrasonication promotes dispersing and dissolving remdesivir resulting in more effective formulations and higher bioavailability.

Advantages of Cyclodextrin Complexes

Cyclodextrins (CDs) are widely used to improve drug efficacy and potency, which means the drug can be administered in the lowest possible dose whilst achieving optimum therapeutic activity.
Drugs formulated into cyclodextrin complexes offer a significantly increased drug solubility, which lowers cytotoxicity by making the drug effective at lower doses. For instance, β-cyclodextrin complexation of ganciclovir improved the drug’s antiviral activity of on human cytomegalovirus clinical strains. Subsequently, the increased drug potency resulted in a reduced the drug toxicity. Overall, cyclodextrins show a very good absorption rate and reduce drug-induced irritancies. Cyclodextrin inclusion complexes lower the local concentration of the free drug, so that the concentration is below the irritancy threshold. Cyclodextrin inclusion improves drug stability and prevents against incompatibilities. Finally, CD complexes mask drug odour and off-flavours.

High Performance Ultrasonicators for Drug Encapsulation

Hielscher Ultrasonics is long-time experienced in the design, manufacturing, and distribution of high-performance ultrasonic homogenisers for the pharmaceutical, food, and cosmetic industry. Hielscher is proud to be not only hardware supplier, but offers sophisticated consulting and training for ultrasonic applications as well as the installation and operation of ultrasonic systems.
The preparation of high-quality cyclodextrin complexes and other nanostructured drug carriers auch as niosomes, liposomes, solid lipid nanoparticles, or polymeric nanoparticles are processes, in which Hielscher ultrasonic systems excel due to their high reliability, consistent power output, and precise controllability. Hielscher ultrasonicators allow for precise control over all process parameters, such as amplitude, temperature, pressure and sonication energy. The intelligent software automatically protocols all sonication parameters (time, date, amplitude, net energy, total energy, temperature, pressure) on the built-in SD-card.
The robustness of Hielscher’s ultrasonic equipment allows for 24/7 operation at heavy duty and in demanding environments.
The table below gives you an indication of the approximate processing capacity of our ultrasonicators: