Ultrasonically Formulated Famotidine Solid-Lipid Nanoparticles

Famotidine is a common pharmaceutical molecule used in heartburn medications. In order to overcome the poor solubility and the resulting poor bioavailability, famotidine can be formulated into solid-lipid nanoparticles using sonication as encapsulation technique.

Ultrasonically Famotidine-Loaded Solid Lipid Nanoparticles

Sonication is widely used in the production of pharmaceuticals, vaccines and dietary supplements. An important application is the formulation, encapsulation and/or entrapment of bioactive molecules (i.e. drug substance) into nano-structured functional drug delivery systems such as solid-lipid nanoparticles, liposomes, niosomes, inclusion complexes or polymeric nanoparticles.

Famotidine

Famotidine is an H2 receptor blocker and the active compound in the widely used over-the-counter (OTC) heartburn drug Pepcid. Absorption orally is rapid enough, but famotidine can be degraded by stomach acid causing dose reduction until 35.8% after 50 minutes. This drug also undergoes first-pass metabolism which reduced its bio availability only until 40-50%
As of end of April 2020, famotidine is also studied as potential drug to treat patients suffering from the SARS-CoV-2 (coronavirus) caused COVID-19 disease. In a clinical trial, patients with severe coronavirus disease COVID-19 are receiving famotidine intravenously.
Common famotidine containing drugs are known under various brand names such as Pepcid AC, Acid Controller, Pepcid, Acid Reducer (famotidine), Heartburn Prevention, and Heartburn Relief (famotidine).

Ultrasonic Preparation of Solid-Lipid Nanoparticles

The ultrasonic preparation of famotidine-loaded solid lipid nanoparticles (SLNs) is a simple and efficacious technique to formulate a high-quality nano-sized drug delivery system with significantly increased bioavailability.
Zai et al. (2019) prepared solid lipid nanoparticles (SLNs) using the ultrasonically-assisted hot emulsification technique. Glyceryl monostearate and Span 20 (3:1 w/w) mixture were melted at approx. 60°C and added famotidine (2 mg/mL of total vol.). Water containing poloxamer (4mg/mL) was heated also at approx. 60°C and transferred to the molten lipid mixture. The lipid and aqueous phase were mixed by high-shear homogenizer at 5,000 rpm for 5 min, then sonicated with a probe-type ultrasonicator for 5 min.
The results showed that the famotidine-loaded solid lipid nanoparticles had a mean particle size of an average 151,90 ± 26,05 nm and a relatively small size distribution (0,35 ± 0,04). The famotidine-loaded solid lipid nanoparticles had a high entrapment efficiency of 82,30 ± 4,39 % and an increased bioavailability.

TEM image of ultrasonically prepared solid lipid nanoparticles loaded with famotidine (scale bar 100nm)
source: Zai et al. 2019

High-Performance Ultrasonicators for Pharma Formulations

Hielscher Ultrasonics 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 solid lipid nanoparticles, nanostructured lipid carriers, liposomes, niosomes, and cyclodextrin inclusion 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 table below gives you an indication of the approximate processing capacity of our ultrasonicators: