Optimization, and in vitro and in vivo evaluation of etomidate intravenous lipid emulsion

Abstract

The aim of this investigation was to develop an etomidate intravenous lipid emulsion (ETM-ILE) and evaluate its properties in vitro and in vivo . Etomidate (ETM) is a hydrophobic drug, and organic solvents must be added to an etomidate injectable solution (ETM-SOL) to aid dissolution, that causes various adverse reactions on injection. Lipid emulsions are a novel drug formulation that can improve drug loading and reduce adverse reactions. ETM-ILE was prepared using high-pressure homogenization. Univariate experiments were performed to select key conditions and variables. The proportion of oil, egg lecithin, and poloxamer 188 (F68) served as variables for the optimization of the ETM-ILE formulation by central composite design response surface methodology. The optimized formulation had the following characteristics: particle size, 168.0 ± 0.3 nm; polydispersity index, 0.108 ± 0.028; zeta potential, −36.4 ± 0.2 mV; drug loading, 2.00 ± 0.01 mg/mL; encapsulation efficiency, 97.65% ± 0.16%; osmotic pressure, 292 ± 2 mOsmol/kg and pH value, 7.63 ± 0.07. Transmission electron microscopy images showed that the particles were spherical or spheroidal, with a diameter of approximately 200 nm. The stability study suggested that ETM-ILE could store at 4 ± 2 °C or 25 ± 2 °C for 12 months. Safety tests showed that ETM-ILE did not cause hemolysis or serious vascular irritation. The results of the pharmacokinetic study found that ETM-ILE was bioequivalent to ETM-SOL. However, a higher concentration of ETM was attained in the liver, spleen, and lungs after administration of ETM-ILE than after administration of ETM-SOL. This study found that ETM-ILE had great potential for clinical applications.

Nanoencapsulation of general anaesthetics

“…The homogenization or sonication of the mixture in water creates an emulsion ideal for delivering hydrophobic drugs such as propofol. 33,35,[41][42][43] Johnson et al, used soy phosphatidylcholine, glycerol dioleate, and polysorbate to create a lipid crystal nano emulsion with a particle size around 118 nm. 33 The propofol 25…”

“…50 Finally, intravenous lipid emulsions were developed and exhibited a similar Nanoscale Advances Review pharmacokinetic prole to commercial etomidate as it showed low haemolysis but with low vascular irritation. 41…”

“…The homogenization or sonication of the mixture in water creates an emulsion ideal for delivering hydrophobic drugs such as propofol. 33,35,41–43 Johnson et al , used soy phosphatidylcholine, glycerol dioleate, and polysorbate to create a lipid crystal nano emulsion with a particle size around 118 nm. 33 The propofol concentration in this nano formula was 10 mg mL −1 (which is similar to propofol concentration in commercial Lipuro) which exhibited a LORR duration of 7.5 min compared to 6.3 min for Lipuro.…”

Comparative study of midazolam and fentanyl for the prevention of etomidate-induced myoclonus

“…Pain on injection, venous irritation, and hemolysis were virtually abolished by the new fat emulsion preparation of etomidate. 4 but it failed to reduce the incidence of myoclonus. Myoclonic movements after etomidate injection develop in nearly 80% of the non-pre-medicated patients which may lead to regurgitation and aspiration in the non-fasting patients, may even raise the risk of prolapse of the vitreous in patients with open globe injury.…”

Preparation and Optimization of Quick/Slow-release Bilayered Tablets of Prazosin HCl using DoE and PCA

“…PCA and Design of experiments (DoE) have been proved as extremely utile tools for the construction of design spaces, an important component of control strategy for QbD [8][9][10][11][12]. Central composite design is the most frequently used design in the response surface optimization technique [13][14][15][16]. Prazosin HCl (PZH) is a sympatholytic drug used to treat high blood pressure, anxiety and post-traumatic stress disorder.…”