Ultrasonic Nano-Encapsulation of Ivermectin
Ivermectin, a member of the avermectin drug class, is an anti-parasitic drug used mostly to treat roundworm infections. It works by by binding to and activating glutamate-gated chloride channel receptors (GluClRs) of the parasites, thereby paralyzing and killing them. During the research for a cure against COVID-19, the disease caused by the novel coronavirus SARS-CoV-2, ivermectin came into the focus of pharma research as it killed the SARS-CoV-2 coronavirus within 40hr in “in vitro” tests. Aa an already FDA-approved drug, the pharmacology of ivermectin is well known and the drug would be readily available for fast implementation of COVID-19 mass treatment. (status Apr, 12th 2020).
Ultrasonic Encapsulation of Ivermectin
Nano-sized drug carriers such as solid-lipid nanoparticles (SLNs), liposomes and cyclodextrin complexes are known to improve drug delivery and bioavailability, to provide a slow / sustained drug release, and to protect the bioactive molecule against degradation. As ivermectin is incompatible with various common excipients, which requires an alternative formulation. Furthermore, ivermectin is prone to be degraded by light, oxygen and hydrolysis, so that encapsulation helps to protect and stabilise the drug compound. Solid-lipid nanoparticles, liposomes or cyclodextrin-based ivermectin formulations show good results offering protection against degradation as well as improved solubility and stability.
The ultrasonically prepared ivermectin-SLNs showed a relatively high encapsulation efficiency (EE) with a narrow particle size distribution. The release study displayed slow and sustained release patterns for ivermectin-SLNs.
Ultrasonic Encapsulation of Ivermectin in Solid-Lipid Nanoparticles
Ultrasonically promoted formation of solid-lipid nanoparticles is a well-known technique used to formulate pharmaceutical complexes with a high absorption rate and bioaccessibility, low cytotoxicity, and sustained drug release.
Guo and coworkers (Guo et al. 2017) showed in their research that ultrasonic encapsulation of ivermectin in solid-lipid nanoparticles (SLNs) resulted in amorphous ivermectin particles within the SLNs and displayed prolonged release of the drug molecules from the SLNs without burst release due to high encapsulation efficiency (EE).
The preparation of ivermectin SLNs was performed in order to the following protocol:
SLNs were prepared by hot homogenisation, followed by ultrasonication. Briefly, palmitic acid (0.5 g) was melted in a 30-ml glass vial by a magnetic stirrer at 75ºC. Ivermectin (0.09 g) was then dissolved in the melted lipid. The lipid phase was subsequently poured into 15mL of boiling aqueous solution with 1% PVA (w/v) under magnetic stirring at 300rpm for 10 min to form a coarse oil-in-water emulsion. After that, the emulsion was sonicated for 5 min, and then 15 mL of cold water (4ºC) was immediately poured into to obtain the ivermectin-SLNs. Control SLNs were prepared following the same protocol without the addition of ivermectin.
Liposomal Avermectin Formulation
Liposomes are composed from one or more phospholipid bilayers. Combining chemically and biologically inert synthetic polymers to produce long-circulating liposomes allows for the preparation of liposomes with prolonged drug circulation time in vivo, thereby enhancing the effectiveness. For example, the duration of efficacy of liposomal avermectin was increased from 21 to 30 days in goats (Sun et al., 2014).
Besides the formulation into solid-lipid nanoparticles, ivermectin has been successfully encapsulated into liposomes and cyclodextrin complexes.
Read more about the ultrasonic formulation of liposomes and cyclodextrin complexes!
- High performance emulsification
- Exact control over lipid particle size and load
- High load of active substances
- Exact control over process parameters
- Fast Process
- Non-thermal, precise temp control
- Linear Scalability
- Process standardisation / GMP
- Autoclavable probes and reactors
- CIP / SIP
High Performance Ultrasonicators
High-Performance Ultrasonicators for Pharma Formulations
Hielscher Ultrasonic is long-time experienced in the design, manufacturing, distribution and service of high-performance ultrasonic homogenisers for the pharmaceutical and food industry.
The preparation of high-quality liposomes, solid lipid nanoparticles, polymeric nanoparticles and cyclodextrin complexes are processes, which Hielscher ultrasonic systems are used with high reliability and superior quality output. 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:
|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|
Contact Us! / Ask Us!
- Dawei Guo, Dandan Dou, Xinyu Li, Qian Zhang, Zohaib Ahmed Bhutto, Liping Wang (2018): Ivermectin-loaded solid lipid nanoparticles: preparation, characterisation, stability and transdermal behaviour. Artificial Cells, Nanomedicine, and Biotechnology. An International Journal Volume 46, Issue 2, 2018.
- Sun XF, Zhang YQ, Xian-Hui XU, et al. (2014): Study on pharmacokinetics of avermectin nanometre liposomes in goats. Prog Vet Med 35:71–4
- Leon Caly; Julian D. Druce; Mike G. Catton; David A. Jans; Kylie M. Wagstaff (2020): The FDA-approved Drug Ivermectin inhibits the replication of SARS-CoV-2 in vitro. Antiviral Research, Pre-proof available online 3 April 2020.
Facts Worth Knowing
Ivermectin is a mixture containing at least 90% 5-O-demethyl-22,23-dihydroavermectin and less than 10% 5-O-demethyl-25-de(1-methylpropyl)-22,23-dihydro-25-(1-
methylethyl)avermectin, generally referred to as 22,23-dihydroavermectin.
Ivermectin is available as a generic drug in a 3mg tablet formulation. Common brand names of ivermectin are Driponin and Scrabioral in Germany, Heartgard, Sklice and Stromectol in the United States, and Mectizan in Canada to name just a few.
Avermectins are disaccharides (ivermectin, doramectin) or monosaccharides (selamectin). Avermectins are a series of macrocyclic lactone derivatives with antiparasitic effects, mainly used to treat nematode infections. Insoluble in water, avermectin can be solubilised in methanol and 95% ethanol.